Sample records for afferent inhibition sai

  1. Dynamic modulation of corticospinal excitability and short-latency afferent inhibition during onset and maintenance phase of selective finger movement.

    PubMed

    Cho, Hyun Joo; Panyakaew, Pattamon; Thirugnanasambandam, Nivethida; Wu, Tianxia; Hallett, Mark

    2016-06-01

    During highly selective finger movement, corticospinal excitability is reduced in surrounding muscles at the onset of movement but this phenomenon has not been demonstrated during maintenance of movement. Sensorimotor integration may play an important role in selective movement. We sought to investigate how corticospinal excitability and short-latency afferent inhibition changes in active and surrounding muscles during onset and maintenance of selective finger movement. Using transcranial magnetic stimulation (TMS) and paired peripheral stimulation, input-output recruitment curve and short-latency afferent inhibition (SAI) were measured in the first dorsal interosseus and abductor digiti minimi muscles during selective index finger flexion. Motor surround inhibition was present only at the onset phase, but not at the maintenance phase of movement. SAI was reduced at onset but not at the maintenance phase of movement in both active and surrounding muscles. Our study showed dynamic changes in corticospinal excitability and sensorimotor modulation for active and surrounding muscles in different movement states. SAI does not appear to contribute to motor surround inhibition at the movement onset phase. Also, there seems to be different inhibitory circuit(s) other than SAI for the movement maintenance phase in order to delineate the motor output selectively when corticospinal excitability is increased in both active and surrounding muscles. This study enhances our knowledge of dynamic changes in corticospinal excitability and sensorimotor interaction in different movement states to understand normal and disordered movements. Published by Elsevier Ireland Ltd.

  2. Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli

    PubMed Central

    2012-01-01

    Background The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. Methods This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Results Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent

  3. Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

    PubMed

    Doeltgen, Sebastian H; Young, Jessica; Bradnam, Lynley V

    2016-08-01

    The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

  4. Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults.

    PubMed

    Young-Bernier, Marielle; Tanguay, Annick N; Davidson, Patrick S R; Tremblay, François

    2014-01-01

    Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.

  5. Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults

    PubMed Central

    Young-Bernier, Marielle; Tanguay, Annick N.; Davidson, Patrick S. R.; Tremblay, François

    2014-01-01

    Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS. PMID:25147523

  6. The firing characteristics of foot sole cutaneous mechanoreceptor afferents in response to vibration stimuli.

    PubMed

    Strzalkowski, Nicholas D J; Ali, R Ayesha; Bent, Leah R

    2017-10-01

    Single unit microneurography was used to record the firing characteristics of the four classes of foot sole cutaneous afferents [fast and slowly adapting type I and II (FAI, FAII, SAI, and SAII)] in response to sinusoidal vibratory stimuli. Frequency (3-250 Hz) and amplitude (0.001-2 mm) combinations were applied to afferent receptive fields through a 6-mm diameter probe. The impulses per cycle, defined as the number of action potentials evoked per vibration sine wave, were measured over 1 s of vibration at each frequency-amplitude combination tested. Afferent entrainment threshold (lowest amplitude at which an afferent could entrain 1:1 to the vibration frequency) and afferent firing threshold (minimum amplitude for which impulses per cycle was greater than zero) were then obtained for each frequency. Increases in vibration frequency are generally associated with decreases in expected impulses per cycle ( P < 0.001), but each foot sole afferent class appears uniquely tuned to vibration stimuli. FAII afferents tended to have the lowest entrainment and firing thresholds ( P < 0.001 for both); however, these afferents seem to be sensitive across frequency. In contrast to FAII afferents, SAI and SAII afferents tended to demonstrate optimal entrainment to frequencies below 20 Hz and FAI afferents faithfully encoded frequencies between 8 and 60 Hz. Contrary to the selective activation of distinct afferent classes in the hand, application of class-specific frequencies in the foot sole is confounded due to the high sensitivity of FAII afferents. These findings may aid in the development of sensorimotor control models or the design of balance enhancement interventions. NEW & NOTEWORTHY Our work provides a mechanistic look at the capacity of foot sole cutaneous afferents to respond to vibration of varying frequency and amplitude. We found that foot sole afferent classes are uniquely tuned to vibration stimuli; however, unlike in the hand, they cannot be independently

  7. Reduced Short- and Long-Latency Afferent Inhibition Following Acute Muscle Pain: A Potential Role in the Recovery of Motor Output.

    PubMed

    Burns, Emma; Chipchase, Lucinda Sian; Schabrun, Siobhan May

    2016-02-13

    . Corticomotor output is reduced in response to acute muscle pain, yet the mechanisms that underpin this effect remain unclear. Here the authors investigate the effect of acute muscle pain on short-latency afferent inhibition, long-latency afferent inhibition, and long-interval intra-cortical inhibition to determine whether these mechanisms could plausibly contribute to reduced motor output in pain. . Observational same subject pre-post test design. . Neurophysiology research laboratory. . Healthy, right-handed human volunteers (n = 22, 9 male; mean age ± standard deviation, 22.6 ± 7.8 years). . Transcranial magnetic stimulation was used to assess corticomotor output, short-latency afferent inhibition, long-latency afferent inhibition, and long-interval intra-cortical inhibition before, during, immediately after, and 15 minutes after hypertonic saline infusion into right first dorsal interosseous muscle. Pain intensity and quality were recorded using an 11-point numerical rating scale and the McGill Pain Questionnaire. . Compared with baseline, corticomotor output was reduced at all time points (p = 0.001). Short-latency afferent inhibition was reduced immediately after (p = 0.039), and long-latency afferent inhibition 15 minutes after (p = 0.035), the resolution of pain. Long-interval intra-cortical inhibition was unchanged at any time point (p = 0.36). . These findings suggest short- and long-latency afferent inhibition, mechanisms thought to reflect the integration of sensory information with motor output at the cortex, are reduced following acute muscle pain. Although the functional relevance is unclear, the authors hypothesize a reduction in these mechanisms may contribute to the restoration of normal motor output after an episode of acute muscle pain. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Inhibition of Repulsive Guidance Molecule, RGMa, Increases Afferent Synapse Formation with Auditory Hair Cells

    PubMed Central

    Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S.B.

    2017-01-01

    The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. PMID:24123853

  9. Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion

    PubMed Central

    Hayes, Heather Brant; Chang, Young-Hui

    2012-01-01

    Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord–hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations. PMID:22442562

  10. Oligosynaptic inhibition of group Ia afferents from brachioradialis to triceps brachii motor neurons in humans.

    PubMed

    Sato, Toshiaki; Nito, Mitsuhiro; Suzuki, Katsuhiko; Fujii, Hiromi; Hashizume, Wataru; Miyasaka, Takuji; Shindo, Masaomi; Naito, Akira

    2018-01-01

    This study examines effects of low-threshold afferents from the brachioradialis (BR) on excitability of triceps brachii (TB) motor neurons in humans. We evaluated the effects using a post stimulus time histogram (PSTH) and electromyogram averaging (EMG-A) methods in 13 healthy human participants. Electrical conditioning stimulation to the radial nerve branch innervating BR with the intensity below the motor threshold was delivered. In the PSTH study, the stimulation produced a trough (inhibition) in 36/69 TB motor units for all the participants. A cutaneous stimulation never provoked such inhibition. The central latency of the inhibition was 1.5 ± 0.5 ms longer than that of the homonymous facilitation. In the EMG-A study, the stimulation produced inhibition in EMG-A of TB in all participants. The inhibition diminished with a tonic vibration stimulation to BR. These findings suggest that oligosynaptic inhibition mediated by group Ia afferents from BR to TB exists in humans. Muscle Nerve 57: 122-128, 2018. © 2017 Wiley Periodicals, Inc.

  11. OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

    PubMed

    Collins, Valerie M; Daly, Donna M; Liaskos, Marina; McKay, Neil G; Sellers, Donna; Chapple, Christopher; Grundy, David

    2013-11-01

    To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures. Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release. These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves. © 2013 The Authors. BJU International © 2013 BJU International.

  12. Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

    PubMed

    Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

    2003-09-01

    The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

  13. Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

    PubMed

    Hao, Man-Zhao; Xu, Shao-Qin; Hu, Zi-Xiang; Xu, Fu-Liang; Niu, Chuan-Xin M; Xiao, Qin; Lan, Ning

    2017-07-14

    Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. Our

  14. Influence of locomotor muscle afferent inhibition on the ventilatory response to exercise in heart failure.

    PubMed

    Olson, Thomas P; Joyner, Michael J; Eisenach, John H; Curry, Timothy B; Johnson, Bruce D

    2014-02-01

    What is the central question of this study? Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients. What is the main finding and its importance? Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients. Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo-controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant-work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor-sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide (P(aCO(2)) and a decrease in oxygen (P(aO(2)); P < 0.05 for both) at rest. The control subjects demonstrated no change in P(aCO(2)), P(aO(2)), ventilation, tidal volume or respiratory rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6 versus 44 ± 3 l min(-1), P < 0.05) due

  15. Attention modulates specific motor cortical circuits recruited by transcranial magnetic stimulation.

    PubMed

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2017-09-17

    Skilled performance and acquisition is dependent upon afferent input to motor cortex. The present study used short-latency afferent inhibition (SAI) to probe how manipulation of sensory afference by attention affects different circuits projecting to pyramidal tract neurons in motor cortex. SAI was assessed in the first dorsal interosseous muscle while participants performed a low or high attention-demanding visual detection task. SAI was evoked by preceding a suprathreshold transcranial magnetic stimulus with electrical stimulation of the median nerve at the wrist. To isolate different afferent intracortical circuits in motor cortex SAI was evoked using either posterior-anterior (PA) or anterior-posterior (PA) monophasic current. In an independent sample, somatosensory processing during the same attention-demanding visual detection tasks was assessed using somatosensory-evoked potentials (SEP) elicited by median nerve stimulation. SAI elicited by AP TMS was reduced under high compared to low visual attention demands. SAI elicited by PA TMS was not affected by visual attention demands. SEPs revealed that the high visual attention load reduced the fronto-central P20-N30 but not the contralateral parietal N20-P25 SEP component. P20-N30 reduction confirmed that the visual attention task altered sensory afference. The current results offer further support that PA and AP TMS recruit different neuronal circuits. AP circuits may be one substrate by which cognitive strategies shape sensorimotor processing during skilled movement by altering sensory processing in premotor areas. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Bicuculline and strychnine suppress the mesencephalic locomotor region-induced inhibition of group III muscle afferent input to the dorsal horn.

    PubMed

    Degtyarenko, A M; Kaufman, M P

    2003-01-01

    We examined the effect of iontophoretic application of bicuculline methiodide and strychnine hydrochloride on the mesencephalic locomotor region (MLR)-induced inhibition of dorsal horn cells in paralyzed cats. The activity of 60 dorsal horn cells was recorded extracellularly in laminae I, II, V-VII of spinal segments L7-S1. Each of the cells was shown to receive group III muscle afferent input as demonstrated by their responses to electrical stimulation of the tibial nerve (mean latency and threshold of activation: 20.1+/-6.4 ms and 15.2+/-1.4 times motor threshold, respectively). Electrical stimulation of the MLR suppressed transmission in group III muscle afferent pathways to dorsal horn cells. Specifically the average number of impulses generated by the dorsal horn neurons in response to a single pulse applied to the tibial nerve was decreased by 78+/-2.8% (n=60) during the MLR stimulation. Iontophoretic application (10-50 nA) of bicuculline and strychnine (5-10 mM) suppressed the MLR-induced inhibition of transmission of group III afferent input to laminae I and II cells by 69+/-5% (n=10) and 29+/-7% (n=7), respectively. Likewise, bicuculline and strychnine suppressed the MLR-induced inhibition of transmission of group III afferent input to lamina V cells by 59+/-13% (n=14) and 39+/-11% (n=10), respectively. Our findings raise the possibility that GABA and glycine release onto dorsal horn neurons in the spinal cord may play an important role in the suppression by central motor command of thin fiber muscle afferent-reflex pathways.

  17. Common theme for drugs effective in overactive bladder treatment: Inhibition of afferent signaling from the bladder

    PubMed Central

    Hood, Brandy; Andersson, Karl-Erik

    2013-01-01

    The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed. PMID:23072271

  18. Acute effects of muscle vibration on sensorimotor integration.

    PubMed

    Lapole, Thomas; Tindel, Jérémy

    2015-02-05

    Projections from the somesthetic cortex are believed to be involved in the modulation of motor cortical excitability by muscle vibration. The aim of the present pilot study was to analyse the effects of a vibration intervention on short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and afferent facilitation (AF), three intracortical mechanisms reflecting sensorimotor integration. Abductor pollicis brevis (APB) SAI, AF and LAI were investigated on 10 subjects by conditioning test transcranial magnetic stimulation pulses with median nerve electrical stimulation at inter-stimuli intervals in the range 15-25 ms, 25-60 ms, and 100-200 ms, respectively. Test motor evoked potentials (MEPs) were compared to unconditioned MEPs. Measurements were performed before and just after 15 min of vibration applied to the muscle belly of APB at a frequency of 80 Hz. SAI and LAI responses were significantly reduced compared to unconditioned test MEPs (P=0.039 and P<0.001, respectively). AF MEP amplitude was greater than SAI and LAI one (P=0.009 and P=0.004, respectively), but not different from test MEP (P=0.511). There was no significant main effect of vibration (P=0.905). However, 4 subjects were clearly identified as responders. Their mean vibration-induced increase was 324 ± 195% in APB SAI MEP amplitude, and 158 ± 53% and 319 ± 80% in AF and LAI, respectively. Significant differences in SAI, AF and LAI vibration-induced changes were found for responders when compared to non-responders (P=0.019, P=0.038, and P=0.01, respectively). A single session of APB vibration may increase sensorimotor integration, via decreased inhibition and increased facilitation. However, such results were not observed for all subjects, suggesting that other factors (such as attention to the sensory inputs) may have played a role. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.

    PubMed

    Chen, W; McRoberts, J A; Marvizón, J C G

    2014-05-16

    Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. Published by Elsevier Ltd.

  20. μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

    PubMed Central

    Chen, Wenling; McRoberts, James A.; Marvizón, Juan Carlos G.

    2014-01-01

    Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund’s adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms. PMID:24583035

  1. Inhibition by spinal mu- and delta-opioid agonists of afferent-evoked substance P release.

    PubMed

    Kondo, Ichiro; Marvizon, Juan Carlos G; Song, Bingbing; Salgado, Frances; Codeluppi, Simone; Hua, Xiao-Ying; Yaksh, Tony L

    2005-04-06

    Opioid mu- and delta-receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and in vivo. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the mu agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) (1 microM) and decreased by the delta agonist [D-Phe2,5]-enkephalin (DPDPE) (1 microM). In vivo, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the kappa agonist trans-(1S,2S)-3,4-dichloro-N-mathyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the mu and delta agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.

  2. Impairment of sensory-motor plasticity in mild Alzheimer's disease.

    PubMed

    Terranova, Carmen; Carmen, Terranova; SantAngelo, Antonino; Antonino, Sant'Angelo; Morgante, Francesca; Francesca, Morgante; Rizzo, Vincenzo; Vincenzo, Rizzo; Allegra, Roberta; Roberta, Allegra; Arena, Maria Grazia; Grazia, Arena Maria; Ricciardi, Lucia; Lucia, Ricciardi; Ghilardi, Marie Felice; Felice, Ghilardi Maria; Girlanda, Paolo; Paolo, Girlanda; Quartarone, Angelo; Angelo, Quartarone

    2013-01-01

    Primary motor cortex (M1) is relatively spared in the early stages of Alzheimer's disease (AD). Aim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI). We studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms. Baseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients. Sensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

    PubMed

    Rudomin, P; Lomelí, J

    2007-01-01

    We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation

  4. Peripheral μ-opioid receptor mediated inhibition of calcium signaling and action potential-evoked calcium fluorescent transients in primary afferent CGRP nociceptive terminals.

    PubMed

    Baillie, Landon D; Schmidhammer, Helmut; Mulligan, Sean J

    2015-06-01

    While μ-opioid receptor (MOR) agonists remain the most powerful analgesics for the treatment of severe pain, serious adverse side effects that are secondary to their central nervous system actions pose substantial barriers to therapeutic use. Preclinical and clinical evidence suggest that peripheral MORs play an important role in opioid analgesia, particularly under inflammatory conditions. However, the mechanisms of peripheral MOR signaling in primary afferent pain fibres remain to be established. We have recently introduced a novel ex vivo optical imaging approach that, for the first time, allows the study of physiological functioning within individual peripheral nociceptive fibre free nerve endings in mice. In the present study, we found that MOR activation in selectively identified, primary afferent CGRP nociceptive terminals caused inhibition of N-type Ca(2+) channel signaling and suppression of action potential-evoked Ca(2+) fluorescent transients mediated by 'big conductance' Ca(2+)-activated K(+) channels (BKCa). In the live animal, we showed that the peripherally acting MOR agonist HS-731 produced analgesia and that BKCa channels were the major effectors of the peripheral MOR signaling. We have identified two key molecular transducers of MOR activation that mediate significant inhibition of nociceptive signaling in primary afferent terminals. Understanding the mechanisms of peripheral MOR signaling may promote the development of pathway selective μ-opioid drugs that offer improved therapeutic profiles for achieving potent analgesia while avoiding serious adverse central side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Development and validation of a stock addiction inventory (SAI).

    PubMed

    Youn, HyunChul; Choi, Jung-Seok; Kim, Dai-Jin; Choi, Sam-Wook

    2016-01-01

    Investing in financial markets is promoted and protected by the government as an essential economic activity, but can turn into a gambling addiction problem. Until now, few scales have widely been used to identify gambling addicts in financial markets. This study aimed to develop a self-rating scale to distinguish them. In addition, the reliability and validity of the stock addiction inventory (SAI) were demonstrated. A set of questionnaires, including the SAI, south oaks gambling screen (SOGS), and DSM-5 diagnostic criteria, for gambling disorder was completed by 1005 participants. Factor analysis, internal consistency testing, t tests, analysis of variance, and partial correlation analysis were conducted to verify the reliability and validity of SAI. The factor analysis results showed the final SAI consisting of two factors and nine items. The internal consistency and concurrent validity of SAI were verified. The Cronbach's α for the total scale was 0.892, and the SAI and its factors were significantly correlated with SOGS. This study developed a specific scale for financial market investments or trading; this scale proved to be reliable and valid. Our scale expands the understanding of gambling addiction in financial markets and provides a diagnostic reference.

  6. Cortical presynaptic control of dorsal horn C-afferents in the rat.

    PubMed

    Moreno-López, Yunuen; Pérez-Sánchez, Jimena; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

  7. Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

    PubMed Central

    Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

  8. Modulation of the masseteric reflex by gastric vagal afferents.

    PubMed

    Pettorossi, V E

    1983-04-01

    Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

  9. Presynaptic Inhibition of Diverse Afferents to the Locus Coeruleus by Kappa Opiate Receptors: a Novel Mechanism for Regulating the Central Norepinephrine System

    PubMed Central

    Kreibich, Arati S.; Reyes, Beverly A. S.; Curtis, Andre L.; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J.; Valentino, Rita J.

    2008-01-01

    The norepinephrine nucleus, locus coeruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAA), corticotropin-releasing factor (CRF) and endogenous opioids acting at μ-opiate receptors. As the LC is also innervated by the endogenous κ-opiate receptor (κ-OR) ligand, dynorphin, and expresses κ-ORs, this study investigated κ-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of κ-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the κ-OR agonist, U50488, into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the κ-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that κ-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-NE system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate κ-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders or disorders characterized by abnormal sensory responses, such as autism. PMID:18562623

  10. Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

    PubMed

    Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2008-06-18

    The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

  11. The Regularity of Sustained Firing Reveals Two Populations of Slowly Adapting Touch Receptors in Mouse Hairy Skin

    PubMed Central

    Wellnitz, Scott A.; Lesniak, Daine R.; Gerling, Gregory J.

    2010-01-01

    Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell–neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin–nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 ± 0.09) and SAII responses (0.21 ± 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein–expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin–nerve recordings for genetic dissection of touch receptor mechanisms. PMID:20393068

  12. Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients

    PubMed Central

    Di Lorenzo, Francesco; Martorana, Alessandro; Ponzo, Viviana; Bonnì, Sonia; D'Angelo, Egidio; Caltagirone, Carlo; Koch, Giacomo

    2013-01-01

    The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD. PMID:23423358

  13. Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

    PubMed

    Baev, K V; Esipenko, V B; Shimansky, Y P

    1991-01-01

    Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent

  14. Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex

    PubMed Central

    Large, Adam M.; Vogler, Nathan W.; Mielo, Samantha; Oswald, Anne-Marie M.

    2016-01-01

    Throughout the brain, the recruitment of feedforward and recurrent inhibition shapes neural responses. However, disentangling the relative contributions of these often-overlapping cortical circuits is challenging. The piriform cortex provides an ideal system to address this issue because the interneurons responsible for feedforward and recurrent inhibition are anatomically segregated in layer (L) 1 and L2/3 respectively. Here we use a combination of optical and electrical activation of interneurons to profile the inhibitory input received by three classes of principal excitatory neuron in the anterior piriform cortex. In all classes, we find that L1 interneurons provide weaker inhibition than L2/3 interneurons. Nonetheless, feedforward inhibitory strength covaries with the amount of afferent excitation received by each class of principal neuron. In contrast, intracortical stimulation of L2/3 evokes strong inhibition that dominates recurrent excitation in all classes. Finally, we find that the relative contributions of feedforward and recurrent pathways differ between principal neuron classes. Specifically, L2 neurons receive more reliable afferent drive and less overall inhibition than L3 neurons. Alternatively, L3 neurons receive substantially more intracortical inhibition. These three features—balanced afferent drive, dominant recurrent inhibition, and differential recruitment by afferent vs. intracortical circuits, dependent on cell class—suggest mechanisms for olfactory processing that may extend to other sensory cortices. PMID:26858458

  15. Varre-Sai: The Recent Brazilian Fall

    NASA Astrophysics Data System (ADS)

    Zucolotto, M. E.; Antonello, L. L.; Varela, M. E.; Scorzelli, R. B.; Munayco, P.; dos Santos, E.; Ludka, Isabel P.

    2012-12-01

    Varre-Sai, the most recent Brazilian meteorite fall, on June 19th, 2010 at Varre-Sai, in Rio de Janeiro State, Brazil (20°51'41″S; 41°44'.80″W). At least eight masses (total ~3.5 kg) were recovered. Most are totally covered by fusion crust. The exposed interior is of light-grey colour with a few dark shock veins. Five thin polished and etched sections were prepared from a slice weighing 35 g on deposit at the National Museum/UFRJ. It consists mostly of chondrules ranging in size from 0.35 to ~2.2 mm, and chondrule fragments enclosed in a crystalline matrix. The matrix consists of tiny isolated subhedral and anhedral crystals and opaque minerals that are intergrown with broken chondrules. The chondritic texture is poorly defined with chondrule textures that vary from non-porphyritic to porphyritic ones. The essential minerals are olivine (Fa25±0.2) and low-Ca pyroxene (Fa21.66±0.2Wo1.4). Accessory minerals are plagioclase, apatite, Fe-Ni metal phases, troilite, chromite and magnetite. Mössbauer spectroscopy analysis confirms that the mineral phases are olivine, pyroxene, troilite and kamacite/taenite. Chemical data indicate that Varre-Sai is a member of the low iron L chondrite group. The observed texture and mineral phases led us to classify Varre-Sai as an equilibrated petrologic type 5. The shock features of the minerals (undulatory extinction, planar structure and numerous cracks), as well as plagioclase partial or totally transformed to maskelynite, suggest a shock stage S4. Also, some post-impact metamorphic processes could be inferred from the meta-sulfide conjoint grains that show complex mixtures of kamacite-taenite-tetrataenite and troilite. The occurrence of veins crosscutting the studied sections indicates that Varre-Sai was affected by a late fracturing event. Sealing of these fractures must have been a fast process, as shown by troilite globule textures pointing towards rapid solidification. The meteorite name was approved by the Nomenclature

  16. Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

    PubMed Central

    Matsumoto, Misaki; Xie, Weijiao; Inoue, Makoto; Ueda, Hiroshi

    2007-01-01

    Background We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized. Results Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I–III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, Aδ- and Aβ-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests. Conclusion These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition. PMID:18088441

  17. Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-Induced antihyperalgesia.

    PubMed

    Radhakrishnan, Rajan; Sluka, Kathleen A

    2005-10-01

    In this study we investigated the involvement of cutaneous versus knee joint afferents in the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by differentially blocking primary afferents with local anesthetics. Hyperalgesia was induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency to heat before and 4 hours after injection. Skin surrounding the inflamed knee joint was anesthetized using an anesthetic cream (EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed knee joint, and low or high frequency TENS was applied. Control experiments were done using vehicles. In control and EMLA groups, both low and high frequency TENS completely reversed hyperalgesia. However, injection of lidocaine into the knee joint prevented antihyperalgesia produced by both low and high frequency TENS. Recordings of cord dorsum potentials showed that both low and high frequency TENS at sensory intensity activates only large diameter afferent fibers. Increasing intensity to twice the motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both high and low frequency TENS, confirming a loss of large diameter primary afferent input after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous afferents, prevents the antihyperalgesia effects of TENS. We conclude that large diameter primary afferent fibers from deep tissue are required and that activation of cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous afferent activation. In this study by

  18. Mechanisms of reflex bladder activation by pudendal afferents

    PubMed Central

    Woock, John P.; Yoo, Paul B.

    2011-01-01

    Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by −25% to −39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder

  19. Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

    PubMed

    Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H

    2017-05-01

    Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed

  20. The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

    PubMed

    Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

    1999-03-01

    1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

  1. The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat

    PubMed Central

    Pettorossi, V E; Torre, G Della; Bortolami, R; Brunetti, O

    1999-01-01

    The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a ‘12-train’ series, an increasing inhibition. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots. PMID:10050025

  2. Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

    PubMed Central

    2012-01-01

    Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877

  3. Phase correlated adequate afferent action potentials as a drive of human spinal oscillators.

    PubMed

    Schalow, G

    1993-12-01

    1. By recording, with 2 pairs of wire electrodes, single-fibre action potentials (APs) from lower sacral nerve roots of a brain-dead human and a patient with spinal cord lesion, impulse patterns of afferent APs and impulse trains of oscillatory firing motoneurons could be identified and correlated. 2. Two highly activated secondary muscle spindle afferents increased and decreased their activity at about 0.3 Hz. The duration of the doublet interspike interval of a secondary spindle afferent fibre showed no correlation to the oscillation period of the motoneuron. 3. A continuously oscillatory firing motoneuron innervating the external and sphincter showed more transient breaks with the reduction of the number of phase correlated APs from 2 spindle afferents, indicating a looser oscillation. A transient brake of a 157 msec period alpha 2-oscillation could be correlated to the shift of a interspike interval distribution peak from 150 to 180 msec of the adequate afferent input, which suggests a transient loss of the necessary phase relation. 4. Oscillatory firing alpha 2-motoneurons innervating the external bladder and anal sphincters fired independently according to their phase correlated APs from the urinary bladder stretch receptor and muscle spindle afferents respectively; the bladder motoneuron slightly inhibited the anal motoneuron. 5. Receptors of the afferents and innervation sites of oscillatory firing motoneurons could be located within the urinary tract and the anal canal.

  4. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

    PubMed Central

    Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

    2006-01-01

    Glutamate acts at central synapses via ionotropic (iGluR – NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed. PMID:16945965

  5. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors.

    PubMed

    Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

    2006-11-15

    Glutamate acts at central synapses via ionotropic (iGluR--NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed.

  6. Efferent-Mediated Responses in Vestibular Nerve Afferents of the Alert Macaque

    PubMed Central

    Sadeghi, Soroush G.; Goldberg, Jay M.; Minor, Lloyd B.; Cullen, Kathleen E.

    2009-01-01

    The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320°/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (∼10 spikes/s) than in regular afferents (∼2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50° upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition. PMID:19091917

  7. Efferent-mediated responses in vestibular nerve afferents of the alert macaque.

    PubMed

    Sadeghi, Soroush G; Goldberg, Jay M; Minor, Lloyd B; Cullen, Kathleen E

    2009-02-01

    The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320 degrees/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (approximately 10 spikes/s) than in regular afferents (approximately 2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50 degrees upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition.

  8. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    PubMed Central

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

  9. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    PubMed

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  10. Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

    PubMed

    Valdés-Baizabal, Catalina; Soto, Enrique; Vega, Rosario

    2015-01-01

    The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA) plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

  11. Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes.

    PubMed

    Reed-Geaghan, Erin G; Wright, Margaret C; See, Lauren A; Adelman, Peter C; Lee, Kuan Hsien; Koerber, H Richard; Maricich, Stephen M

    2016-04-13

    The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell-neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived Merkel cells. Transgenic mice lacking Merkel cells had normal dorsal root ganglion (DRG) neuron numbers, but fewer DRG neurons expressed the SAI markers TrkB, TrkC, and Ret. Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function. Skin- and Merkel cell-specific deletion of Bdnf during embryogenesis, but not postnatal Bdnf deletion or Ntf3 deletion, reproduced these results. Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions where Bdnf was deleted in embryonic Merkel cells. We conclude that BDNF produced by Merkel cells during a precise embryonic period guides SAI neuron development, providing the first direct evidence that the skin instructs sensory neuron molecular and functional maturation. Peripheral sensory neurons show incredible phenotypic and functional diversity that is initiated early by cell-autonomous and local environmental factors found within the DRG. However, the contribution of target tissues to subsequent sensory neuron development remains unknown. We show that Merkel cells are required for the molecular and functional maturation of the SAI neurons that innervate them. We also show that this process is controlled by BDNF signaling. These findings provide new insights into the regulation of somatosensory neuron development and reveal a novel way in which Merkel cells participate in mechanosensation. Copyright © 2016 the authors 0270-6474/16/364362-15$15.00/0.

  12. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

    PubMed Central

    Longhurst, John C.

    2013-01-01

    Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

  13. Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

    PubMed Central

    Sidhu, Simranjit K.; Weavil, Joshua C.; Mangum, Tyler S.; Jessop, Jacob E.; Richardson, Russell S.; Morgan, David E.; Amann, Markus

    2017-01-01

    Objective To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. Methods Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. Results While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13 ± 3% higher (P < 0.05), resulting in a decrease in MEP/CMEP (P < 0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (−53 ± 3% vs. −39 ± 3%; P < 0.01), the reduction in voluntary muscle activation was smaller (−2 ± 2% vs. −10 ± 2%; P < 0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13 ± 3% and 25 ± 6% in FENT (P < 0.05). Conclusion During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. Significance Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans. PMID:27866119

  14. Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise.

    PubMed

    Sidhu, Simranjit K; Weavil, Joshua C; Mangum, Tyler S; Jessop, Jacob E; Richardson, Russell S; Morgan, David E; Amann, Markus

    2017-01-01

    To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13±3% higher (P<0.05), resulting in a decrease in MEP/CMEP (P<0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (-53±3% vs. -39±3%; P<0.01), the reduction in voluntary muscle activation was smaller (-2±2% vs. -10±2%; P<0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13±3% and 25±6% in FENT (P<0.05). During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans. Copyright © 2016 International Federation of Clinical Neurophysiology. All rights reserved.

  15. Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

    PubMed

    Baev, K V; Esipenko, V B; Shimansky YuP

    1991-01-01

    Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just

  16. Hydrogen peroxide preferentially activates capsaicin-sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder.

    PubMed

    Nicholas, S; Yuan, S Y; Brookes, S J H; Spencer, N J; Zagorodnyuk, V P

    2017-01-01

    There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H 2 O 2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. H 2 O 2 (300-1000 μM) preferentially and potently activated capsaicin-sensitive high threshold afferents but not low threshold stretch-sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin-sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC-030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N-(2-aminoethyl)-N-[[3-methoxy-4-(phenylmethoxy)phenyl]methyl]thiophene-2-carboxamide, significantly inhibited the H 2 O 2 -induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H 2 O 2 on high threshold afferents. The findings show that H 2 O 2 , in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long-lasting activation of the majority of capsaicin-sensitive high threshold afferents, but not low threshold stretch-sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin-sensitive afferent fibres are probable targets of ROS released during oxidative stress. © 2016 The British Pharmacological Society.

  17. Hydrogen peroxide preferentially activates capsaicin‐sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder

    PubMed Central

    Nicholas, S; Yuan, S Y; Brookes, S J H; Spencer, N J

    2016-01-01

    Background and Purpose There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. Experimental Approach ‘Close‐to‐target’ single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. Key Results H2O2 (300–1000 μM) preferentially and potently activated capsaicin‐sensitive high threshold afferents but not low threshold stretch‐sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin‐sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC‐030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N‐(2‐aminoethyl)‐N‐[[3‐methoxy‐4‐(phenylmethoxy)phenyl]methyl]thiophene‐2‐carboxamide, significantly inhibited the H2O2‐induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H2O2 on high threshold afferents. Conclusions and Implications The findings show that H2O2, in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long‐lasting activation of the majority of capsaicin‐sensitive high threshold afferents, but not low threshold stretch‐sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin‐sensitive afferent fibres are probable targets of ROS released during oxidative stress. PMID:27792844

  18. Afferent innervation patterns of the saccule in pigeons

    NASA Technical Reports Server (NTRS)

    Zakir, M.; Huss, D.; Dickman, J. D.

    2003-01-01

    The innervation patterns of vestibular saccular afferents were quantitatively investigated in pigeons using biotinylated dextran amine as a neural tracer and three-dimensional computer reconstruction. Type I hair cells were found throughout a large portion of the macula, with the highest density observed in the striola. Type II hair cells were located throughout the macula, with the highest density in the extrastriola. Three classes of afferent innervation patterns were observed, including calyx, dimorph, and bouton units, with 137 afferents being anatomically reconstructed and used for quantitative comparisons. Calyx afferents were located primarily in the striola, innervated a number of type I hair cells, and had small innervation areas. Most calyx afferent terminal fields were oriented parallel to the anterior-posterior axis and the morphological polarization reversal line. Dimorph afferents were located throughout the macula, contained fewer type I hair cells in a calyceal terminal than calyx afferents and had medium sized innervation areas. Bouton afferents were restricted to the extrastriola, with multi-branching fibers and large innervation areas. Most of the dimorph and bouton afferents had innervation fields that were oriented dorso-ventrally but were parallel to the neighboring reversal line. The organizational morphology of the saccule was found to be distinctly different from that of the avian utricle or lagena otolith organs and appears to represent a receptor organ undergoing evolutionary adaptation toward sensing linear motion in terrestrial and aerial species.

  19. Botulinum toxin in Migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents

    PubMed Central

    Roshni, Ramachandran; Carmen, Lam; Yaksh Tony, L

    2015-01-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi) -SO capsaicin (2.5 μg/30 μl) or meningeal capsaicin (4 μl of 1mg/ml). Pre-treatment with ipsi-SO BONT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent. PMID:25958249

  20. Plasticity of gastro-intestinal vagal afferent endings.

    PubMed

    Kentish, Stephen J; Page, Amanda J

    2014-09-01

    Vagal afferents are a vital link between the peripheral tissue and central nervous system (CNS). There is an abundance of vagal afferents present within the proximal gastrointestinal tract which are responsible for monitoring and controlling gastrointestinal function. Whilst essential for maintaining homeostasis there is a vast amount of literature emerging which describes remarkable plasticity of vagal afferents in response to endogenous as well as exogenous stimuli. This plasticity for the most part is vital in maintaining healthy processes; however, there are increased reports of vagal plasticity being disrupted in pathological states, such as obesity. Many of the disruptions, observed in obesity, have the potential to reduce vagal afferent satiety signalling which could ultimately perpetuate the obese state. Understanding how plasticity occurs within vagal afferents will open a whole new understanding of gut function as well as identify new treatment options for obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.

    PubMed

    Yan, Jin; Edelmayer, Rebecca M; Wei, Xiaomei; De Felice, Milena; Porreca, Frank; Dussor, Gregory

    2011-01-01

    Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. Approximately 80% of dural-afferent neurons responded to a pH 6.0 application with a rapidly activating and rapidly desensitizing ASIC-like current that often exceeded 20nA in amplitude. Inward currents were observed in response to a wide range of pH values and 30% of the neurons exhibited inward currents at pH 7.1. These currents led to action potentials in 53%, 30% and 7% of the dural afferents at pH 6.8, 6.9 and 7.0, respectively. Small decreases in extracellular pH were also able to generate sustained window currents and sustained membrane depolarizations. Amiloride, a non-specific blocker of ASIC channels, inhibited the peak currents evoked upon application of decreased pH while no inhibition was observed upon application of TRPV1 antagonists. The desensitization time constant of pH 6.0-evoked currents in the majority of dural afferents was less than 500ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Afferent Connectivity of the Zebrafish Habenulae

    PubMed Central

    Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

    2016-01-01

    The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

  3. Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat.

    PubMed

    Manjarrez, E; Rojas-Piloni, J G; Jimenez, I; Rudomin, P

    2000-12-01

    We examined, in the anaesthetised cat, the influence of the neuronal ensembles producing spontaneous negative cord dorsum potentials (nCDPs) on segmental pathways mediating primary afferent depolarisation (PAD) of cutaneous and group I muscle afferents and on Ia monosynaptic activation of spinal motoneurones. The intraspinal distribution of the field potentials associated with the spontaneous nCDPs indicated that the neuronal ensembles involved in the generation of these potentials were located in the dorsal horn of lumbar segments, in the same region of termination of low-threshold cutaneous afferents. During the occurrence of spontaneous nCDPs, transmission from low-threshold cutaneous afferents to second order neurones in laminae III-VI, as well as transmission along pathways mediating PAD of cutaneous and Ib afferents, was facilitated. PAD of Ia afferents was instead inhibited. Monosynaptic reflexes of flexors and extensors were facilitated during the spontaneous nCDPs. The magnitude of the facilitation was proportional to the amplitude of the 'conditioning' spontaneous nCDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous nCDPs and fluctuations of monosynaptic reflexes. Stimulation of low-threshold cutaneous afferents transiently reduced the probability of occurrence of spontaneous nCDPs as well as the fluctuations of monosynaptic reflexes. It is concluded that the spontaneous nCDPs were produced by the activation of a population of dorsal horn neurones that shared the same functional pathways and involved the same set of neurones as those responding monosynaptically to stimulation of large cutaneous afferents. The spontaneous activity of these neurones was probably the main cause of the fluctuations of the monosynaptic reflexes observed under anaesthesia and could provide a dynamic linkage between segmental sensory and motor pathways.

  4. Afferent innervation of the utricular macula in pigeons

    NASA Technical Reports Server (NTRS)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  5. [Acute pancreatitis and afferent loop syndrome. Case report].

    PubMed

    Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

    2013-01-01

    The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

  6. Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

    PubMed

    Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W

    2016-12-01

    Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

  7. Electrophysiological characterization of human rectal afferents

    PubMed Central

    Ng, Kheng-Seong; Brookes, Simon J.; Montes-Adrian, Noemi A.; Mahns, David A.

    2016-01-01

    It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and “inflammatory soup” (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3–25) spikes/s vs. 2 (1–4), P < 0.001] and IS [median 5 (range 2–18) spikes/s vs. 2 (1–4), P < 0.001]. Mechanosensitive “hot spots” were identified in 16 nerves [median threshold 2.0 g (range 1.4–6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4–1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. PMID:27789454

  8. Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Pan, Hui-Lin; Longhurst, John C

    1998-01-01

    Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1–T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 μg kg−1 i.a.), des-Arg9-BK (1 μg kg−1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 μg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.), cyclo-oxygenase inhibition with indomethacin (5 mg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.) after pretreatment with indomethacin (5 mg kg−1 i.v.). We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 ± 0.12 to 1.47 ± 0.37 impulses s−1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 ± 0.02 vs. 0.50 ± 0.18 impulses s−1). HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 ± 0.22 to 1.85 ± 0.5 vs. 0.53 ± 0.16 to 1.09 ± 0.4 impulses s−1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 ± 0.14 to 1.19 ± 0.29 vs. 0.22 ± 0.08 to 0.23 ± 0.07 impulses s−1). Indomethacin significantly reduced the

  9. Changes in Afferent Activity After Spinal Cord Injury

    PubMed Central

    de Groat, William C.; Yoshimura, Naoki

    2010-01-01

    Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

  10. Differential Regulation of Primary Afferent Input to Spinal Cord by Muscarinic Receptor Subtypes Delineated Using Knockout Mice*

    PubMed Central

    Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

    2014-01-01

    Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. PMID:24695732

  11. Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat

    PubMed Central

    Zhou, Shi-Yi; Lu, Yuan-Xu; Owyang, Chung

    2011-01-01

    Hyperglycemia has a profound effect on gastric motility. However, little is known about site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg dL−1 had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg dL−1), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g kg−1) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-L-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia, and in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation. PMID:18356537

  12. Differential central projections of vestibular afferents in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Fang, Q.

    1996-01-01

    The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

  13. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was oftenmore » reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal

  14. Afferent Nerve Regulation of Bladder Function in Health and Disease

    PubMed Central

    de Groat, William C.; Yoshimura, Naoki

    2012-01-01

    The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

  15. Vestibular afferent responses to linear accelerations in the alert squirrel monkey

    NASA Technical Reports Server (NTRS)

    Somps, Christopher J.; Schor, Robert H.; Tomko, David L.

    1994-01-01

    The spontaneous activity of 40 otolith afferents and 44 canal afferents was recorded in 4 alert, intact squirrel monkeys. Polarization vectors and response properties of otolith afferents were determined during static re-orientations relative to gravity and during Earth-horizontal, sinusoidal, linear oscillations. Canal afferents were tested for sensitivity to linear accelerations. For regular otolith afferents, a significant correlation between upright discharge rate and sensitivity to dynamic acceleration in the horizontal plane was observed. This correlation was not present in irregular units. The sensitivity of otolith afferents to both static tilts and dynamic linear acceleration was much greater in irregularly discharging units than in regularly discharging units. The spontaneous activity and static and dynamic response properties of regularly discharging otolith afferents were similar to those reported in barbiturate-anesthetized squirrel monkeys. Irregular afferents also had similar dynamic response properties when compared to anesthetized monkeys. However, this sample of irregular afferents in alert animals had higher resting discharge rates and greater sensitivity to static tilts. The majority of otolith polarization vectors were oriented near the horizontal in the plane of the utricular maculae; however, directions of maximum sensitivity were different during dynamic and static testing. Canal afferents were not sensitive to static tilts or linear oscillations of the head.

  16. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  17. Differential Role of Inhibition in Habituation of Two Independent Afferent Pathways to a Common Motor Output

    ERIC Educational Resources Information Center

    Bristol, Adam S.; Carew, Thomas J.

    2005-01-01

    Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk "Aplysia," the prevailing view is that homosynaptic depression of primary sensory afferents underlies…

  18. Heat pulse excitability of vestibular hair cells and afferent neurons

    PubMed Central

    Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

    2016-01-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

  19. Cholinergic dysfunction and amnesia in patients with Wernicke-Korsakoff syndrome: a transcranial magnetic stimulation study.

    PubMed

    Nardone, Raffaele; Bergmann, Jürgen; De Blasi, Pierpaolo; Kronbichler, Martin; Kraus, Jörg; Caleri, Francesca; Tezzon, Frediano; Ladurner, Gunther; Golaszewski, Stefan

    2010-03-01

    The specific neurochemical substrate underlying the amnesia in patients with Wernicke-Korsakoff syndrome (WKS) is still poorly defined. Memory impairment has been linked to dysfunction of neurons in the cholinergic system. A transcranial magnetic stimulation (TMS) protocol, the short latency afferent inhibition (SAI), may give direct information about the function of some cholinergic pathways in the human motor cortex. In the present study, we measured SAI in eight alcoholics with WKS and compared the data with those from a group of age-matched healthy individuals; furthermore, we correlated the individual SAI values of the WKS patients with memory and other cognitive functions. Mean SAI was significantly reduced in WKS patients when compared with the controls. SAI was increased after administration of a single dose of donezepil in a subgroup of four patients. The low score obtained in the Rey Complex Figure delayed recall test, the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Corsi's Block Span subtest of the WAIS-R documented a severe impairment in the anterograde memory and short-term memory. None of the correlations between SAI values and these neuropsychological tests reached significance. We provide physiological evidence of cholinergic involvement in WKS. However, this putative marker of central cholinergic activity did not significantly correlate with the memory deficit in our patients. These findings suggest that the cholinergic dysfunction does not account for the memory disorder and that damage to the cholinergic system is not sufficient to cause a persisting amnesic syndrome in WKS.

  20. The muscarinic inhibition of the potassium M-current modulates the action-potential discharge in the vestibular primary-afferent neurons of the rat.

    PubMed

    Pérez, C; Limón, A; Vega, R; Soto, E

    2009-02-18

    There is consensus that muscarinic and nicotinic receptors expressed in vestibular hair cells and afferent neurons are involved in the efferent modulation of the electrical activity of the afferent neurons. However the underlying mechanisms of postsynaptic control in neurons are not well understood. In our work we show that the activation of muscarinic receptors in the vestibular neurons modulates the potassium M-current modifying the activity of afferent neurons. Whole-cell patch-clamp recordings were made on vestibular-afferent neurons isolated from Wistar rats (postnatal days 7-10) and held in primary culture (18-24 h). The M-current was studied during its deactivation after depolarizing voltage-clamp pulses. In 68% of the cells studied, those of larger capacitance, the M-current antagonists linopirdine and XE-991 reduced the amplitude of the M-current by 54%+/-7% and 50%+/-3%. The muscarinic-receptor agonist oxotremorine-M also significantly reduced the M-current by 58%+/-12% in the cells. The action of oxotremorine-M was blocked by atropine, thus indicating its cholinergic nature. The erg-channel blocker E-4031 did not significantly modify the M-current amplitude. In current-clamp experiments, linopirdine, XE-991, and oxotremorine-M modified the discharge response to current pulses from single spike to multiple spiking, reducing the adaptation of the electrical discharge. Our results indicate that large soma-size cultured vestibular-afferent neurons (most probably calyx-bearing neurons) express the M-current and that the modulation of this current by activation of muscarinic-receptor reduces its spike-frequency adaptation.

  1. Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.

    PubMed

    Sandler, A D; Schlegel, J F; DeSautel, M G; Maher, J W

    1993-10-01

    Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.

  2. Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice.

    PubMed

    Chen, Shao-Rui; Chen, Hong; Yuan, Wei-Xiu; Wess, Jürgen; Pan, Hui-Lin

    2014-05-16

    Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Edge orientation signals in tactile afferents of macaques

    PubMed Central

    Suresh, Aneesha K.

    2016-01-01

    The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic. PMID:27655968

  4. Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

    PubMed

    Morimoto, H; Matsuda, A; Ohori, M; Fujii, T

    1996-06-01

    We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

  5. TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats

    PubMed Central

    De Schepper, H U; De Winter, B Y; Van Nassauw, L; Timmermans, J-P; Herman, A G; Pelckmans, P A; De Man, J G

    2008-01-01

    Patients with inflammatory bowel disease often suffer from gastrointestinal motility and sensitivity disorders. The aim of the current study was to investigate the role of transient receptor potential of the vanilloid type 1 (TRPV1) receptors in the pathophysiology of colitis-induced pelvic afferent nerve sensitization. Trinitrobenzene sulphate (TNBS) colitis (7.5 mg, 30% ethanol) was induced in Wistar rats 72 h prior to the experiment. Single-fibre recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root. Fibres responding to colorectal distension (CRD) were identified in controls and rats with TNBS colitis. The effect of the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-chlorophyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 0.25–5 mg kg−1) or its vehicle (hydroxypropyl-β-cyclodextrin) was tested on the afferent response to repetitive distensions (60 mmHg). Immunocytochemical staining of TRPV1 and NF200, a marker for A-fibre neurons, was performed in the dorsal root ganglia L6–S1. TNBS colitis significantly increased the response to colorectal distension of pelvic afferent C-fibres. BCTC did not significantly affect the C-fibre response in controls, but normalized the sensitized response in rats with colitis. TNBS colitis increased the spontaneous activity of C-fibres, an effect which was insensitive to administration of BCTC. TNBS colitis had no effect on Aδ-fibres, nor was their activity modulated by BCTC. TNBS colitis caused an immunocytochemical up-regulation of TRPV1 receptors in the cell bodies of pelvic afferent NF200 negative neurons. TRPV1 signalling mediates the colitis-induced sensitization of pelvic afferent C-fibres to CRD, while Aδ-fibres are neither sensitized by colitis nor affected by TRPV1 inhibition. PMID:18755744

  6. Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

    PubMed

    Della Torre, G; Brunetti, O; Pettorossi, V E

    2002-01-01

    The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

  7. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium

    PubMed Central

    Hoover, Donald B.; Shepherd, Angela V.; Southerland, E. Marie; Armour, J. Andrew; Ardell, Jeffrey L.

    2008-01-01

    While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T3 DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T3 DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30–40% of ventricular afferent somata in T3 DRG). About 30% of the ventricular afferent neurons in T2 DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB4. Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters. PMID:18558516

  8. Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium.

    PubMed

    Hoover, Donald B; Shepherd, Angela V; Southerland, E Marie; Armour, J Andrew; Ardell, Jeffrey L

    2008-08-18

    While much is known about the influence of ventricular afferent neurons on cardiovascular function in the dog, identification of the neurochemicals transmitting cardiac afferent signals to central neurons is lacking. Accordingly, we identified ventricular afferent neurons in canine dorsal root ganglia (DRG) and nodose ganglia by retrograde labeling after injecting horseradish peroxidase (HRP) into the anterior right and left ventricles. Primary antibodies from three host species were used in immunohistochemical experiments to simultaneously evaluate afferent somata for the presence of HRP and markers for two neurotransmitters. Only a small percentage (2%) of afferent somata were labeled with HRP. About half of the HRP-identified ventricular afferent neurons in T(3) DRG also stained for substance P (SP), calcitonin gene-related peptide (CGRP), or neuronal nitric oxide synthase (nNOS), either alone or with two markers colocalized. Ventricular afferent neurons and the general population of T(3) DRG neurons showed the same labeling profiles; CGRP (alone or colocalized with SP) being the most common (30-40% of ventricular afferent somata in T(3) DRG). About 30% of the ventricular afferent neurons in T(2) DRG displayed CGRP immunoreactivity and binding of the putative nociceptive marker IB(4). Ventricular afferent neurons of the nodose ganglia were distinct from those in the DRG by having smaller size and lacking immunoreactivity for SP, CGRP, and nNOS. These findings suggest that ventricular sensory information is transferred to the central nervous system by relatively small populations of vagal and spinal afferent neurons and that spinal afferents use a variety of neurotransmitters.

  9. Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

    PubMed

    Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

    2012-04-01

    The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Serotonin and cholecystokinin synergistically stimulate rat vagal primary afferent neurones

    PubMed Central

    Li, Y; Wu, X Y; Owyang, C

    2004-01-01

    Recent studies indicate that cholecystokinin (CCK) and serotonin (5-hydroxytryptamine, 5-HT) act via vagal afferent fibres to mediate gastrointestinal functions. In the present study, we characterized the interaction between CCK and 5-HT in the vagal primary afferent neurones. Single neuronal discharges of vagal primary afferent neurones innervating the duodenum were recorded from rat nodose ganglia. Two groups of nodose ganglia neurones were identified: group A neurones responded to intra-arterial injection of low doses of cholecystokinin octapeptide (CCK-8; 10–60 pmol); group B neurones responded only to high doses of CCK-8 (120–240 pmol), and were also activated by duodenal distention. CCK-JMV-180, which acts as an agonist in high-affinity states and as an antagonist in low-affinity states, dose dependently stimulated group A neurones, but inhibited the effect of the high doses of CCK-8 on group B neurones. Duodenal perfusion of 5-HT evoked dose-dependent increases in nodose neuronal discharges. Some neurones that responded to 5-HT showed no response to either high or low doses of CCK-8. A separate group of nodose neurones that possessed high-affinity CCK type A (CCK-A) receptors also responded to luminal infusion of 5-HT. Further, a subthreshold dose of CCK-8 (i.e. 5 pmol) produced no measurable electrophysiological effects but it augmented the neuronal responses to 5-HT. This potentiation effect of CCK-8 was eliminated by CR 1409. From these results we concluded that the vagal nodose ganglion contains neurones that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurones that express high-affinity CCK-A receptors also express 5-HT3 receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. PMID:15235095

  11. Abnormal corticospinal excitability in patients with disorders of consciousness.

    PubMed

    Lapitskaya, Natallia; Gosseries, Olivia; De Pasqua, Victor; Pedersen, Asger Roer; Nielsen, Joergen Feldbaek; de Noordhout, Alain Maertens; Laureys, Steven

    2013-07-01

    Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Hair cell tufts and afferent innervation of the bullfrog crista ampullaris

    NASA Technical Reports Server (NTRS)

    Myers, Steven F.; Lewis, Edwin R.

    1990-01-01

    Within the bullfrog semicircular canal crista, hair cell tuft types were defined and mapped with the aid of scanning electron microscopy. Dye-filled planar afferent axons had mean distal axonal diameters of 1.6-4.9 microns, highly branched arbors, and contacted 11-24 hair cells. Dye-filled isthmus afferent axons had mean distal axonal diameters of 1.8-7.9 microns, with either small or large field arbors contacting 4-9 or 25-31 hair cells. The estimated mean number of contacts per innervated hair cell was 2.2 for planar and 1.3 for isthmus afferent neurons. Data on evoked afferent responses were available only for isthmus units that were observed to respond to our microrotational stimuli. Of 21 such afferent neurons, eight were successfully dye-filled. Within this sample, high-gain units had large field arbors and lower-gain units had small field arbors. The sensitivity of each afferent neuron was analyzed in terms of noise equivalent input (NEI), the stimulus amplitude for which the afferent response amplitude is just equivalent to the rms deviation of the instantaneous spike rate. NEI for isthmus units varied from 0.63 to 8.2 deg/s; the mean was 3.2 deg/s.

  13. Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis.

    PubMed

    Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A

    2010-09-01

    Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.

  14. Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking.

    PubMed

    Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G; Farina, Dario; Sinkjær, Thomas; Mrachacz-Kersting, Natalie

    2017-01-01

    A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.

  15. Vibratory Adaptation of Cutaneous Mechanoreceptive Afferents

    PubMed Central

    Bensmaïa, S. J.; Leung, Y. Y.; Hsiao, S. S.; Johnson, K. O.

    2007-01-01

    The objective of this study was to investigate the effects of extended suprathreshold vibratory stimulation on the sensitivity of slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. To that end, an algorithm was developed to track afferent absolute (I0) and entrainment (I1) thresholds as they change over time. We recorded afferent responses to periliminal vibratory test stimuli, which were interleaved with intense vibratory conditioning stimuli during the adaptation period of each experimental run. From these measurements, the algorithm allowed us to infer changes in the afferents’ sensitivity. We investigated the stimulus parameters that affect adaptation by assessing the degree to which adaptation depends on the amplitude and frequency of the adapting stimulus. For all three afferent types, I0 and I1 increased with increasing adaptation frequency and amplitude. The degree of adaptation seems to be independent of the firing rate evoked in the afferent by the conditioning stimulus. In the analysis, we distinguished between additive adaptation (in which I0 and I1 shift equally) and multiplicative effects (in which the ratio I1/I0 remains constant). RA threshold shifts are almost perfectly additive. SA1 threshold shifts are close to additive and far from multiplicative (I1 threshold shifts are twice the shifts). PC shifts are more difficult to classify. We used an I0 integrate-and-fire model to study the possible neural mechanisms. A change in transducer gain predicts a multiplicative change in I0 and I1 and is thus ruled out as a mechanism underlying SA1 and RA adaptation. A change in the resting action potential threshold predicts equal, additive change in I0 and I1 and thus accounts well for RA adaptation. A change in the degree of refractoriness during the relative refractory period predicts an additional change in I1 such as that observed for SA1 fibers. We infer that adaptation is caused by an increase in spiking thresholds

  16. Convergence of excitatory and inhibitory hair cell transmitters shapes vestibular afferent responses.

    PubMed

    Holstein, Gay R; Rabbitt, Richard D; Martinelli, Giorgio P; Friedrich, Victor L; Boyle, Richard D; Highstein, Stephen M

    2004-11-02

    The vestibular semicircular canals respond to angular acceleration that is integrated to angular velocity by the biofluid mechanics of the canals and is the primary origin of afferent responses encoding velocity. Surprisingly, some afferents actually report angular acceleration. Our data indicate that hair-cell/afferent synapses introduce a mathematical derivative in these afferents that partially cancels the biomechanical integration and results in discharge rates encoding angular acceleration. We examined the role of convergent synaptic inputs from hair cells to this mathematical differentiation. A significant reduction in the order of the differentiation was observed for low-frequency stimuli after gamma-aminobutyric acid type B receptor antagonist administration. Results demonstrate that gamma-aminobutyric acid participates in shaping the temporal dynamics of afferent responses.

  17. Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit.

    PubMed

    Delpierre, S; Pugnat, C; Duté, N; Jammes, Y

    1995-02-15

    It was previously shown that inspiratory resistive loading (IRL) increases the cerebrospinal fluid (CSF) level of beta endorphin in awake goats, and also that the slower ventilation induced by injection of this substance into the CSF of anesthetized dogs is suppressed after vagotomy. In the present study, performed on anesthetized rabbits, we evaluated the part played by vagal afferents in the ventilatory response to IRL after opioid receptor blockade by naloxone. During unloaded breathing, naloxone injection did not modify baseline ventilation. Conversely, naloxone partially reversed IRL-induced hypoventilation through an increase in respiratory rate. This effect was abolished after either vagotomy or cold blockade of large vagal fibers, but it persisted after procaine blockade of thin vagal fibers. These results suggest that pulmonary stretch receptors, which are connected to some large vagal afferent fibers, would play a major role in the ventilatory response to IRL under opioid receptor inhibition.

  18. Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain123

    PubMed Central

    Daou, Ihab; Beaudry, Hélène; Ase, Ariel R.; Wieskopf, Jeffrey S.; Ribeiro-da-Silva, Alfredo; Mogil, Jeffrey S.

    2016-01-01

    Abstract We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8+ primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch+ mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2+-Arch+mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch+ mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8+ afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. PMID:27022626

  19. Novel Afferent Terminal Structure in the Crista Ampullaris of the Goldfish, Carassius auratus

    NASA Technical Reports Server (NTRS)

    Lanford, Pamela J.; Popper, Arthur N.

    1996-01-01

    Using transmission electron microscopy, we have identified a new type of afferent terminal structure in the crista ampullaris of the goldfish Carassius auratus. In addition to the bouton-type afferent terminals previously described in the ear of this species, the crista also contained enlarged afferent terminals that enveloped a portion of the basolateral hair cell membrane. The hair cell membrane was evaginated and protruded into the afferent terminal in a glove-and-finger configuration. The membranes of the two cells were regularly aligned in the protruded region of the contact and had a distinct symmetrical electron density. The electron-dense profiles of these contacts were easily identified and were present in every crista sampled. In some cases, efferent terminals synapsed onto the afferents at a point where the hair cell protruded into the terminal. The ultrastructural similarities of the goldfish crista afferents to calyx afferents found in amniotes (birds, reptiles, and mammals) are discussed. The results of the study support the hypothesis that structural variation in the vertebrate inner ear may have evolved much earlier in evolution than previously supposed.

  20. Classification of longissimus lumborum muscle spindle afferents in the anaesthetized cat

    PubMed Central

    Durbaba, R; Taylor, A; Ellaway, P H; Rawlinson, S

    2006-01-01

    Recordings have been made from 127 single muscle spindle afferents from the longissimus lumborum muscles of anaesthetized cats. They have been characterized by their responses to passive muscle stretch and the effects of succinylcholine (SCh) and by their sensitivity to vibration. The use of SCh permitted the assessment for each afferent of the influence of bag1 (b1) and bag2 (b2) intrafusal muscle fibres. From this, on the assumption that all afferents were affected by chain (c) fibres, they were classified in four groups: b1b2c (41.9%), b2c (51.4%), b1c (1.3%) and c (5.4%). All the afferents with b1 influence were able to respond one to one to vibration at frequencies above 100 Hz and were considered to belong to primary endings. On the basis of the vibration test, 64% of the b2c type afferents appeared to be primaries and 36% secondaries. Of the units classified as primaries, 41% were designated as b2c and would not therefore be able to respond to dynamic fusimotor activity. The significance of this relatively high proportion of b2c-type spindle primary afferents is discussed in relation to the specialized postural function of the back muscles. PMID:16410280

  1. Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

    PubMed Central

    Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

    2010-01-01

    After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

  2. Allodynia mediated by C-tactile afferents in human hairy skin.

    PubMed

    Nagi, Saad S; Rubin, Troy K; Chelvanayagam, David K; Macefield, Vaughan G; Mahns, David A

    2011-08-15

    We recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz–200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s(−1))--known to excite CT fibres--was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4–6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected. Furthermore

  3. Mu-opioid receptors in nociceptive afferents produce a sustained suppression of hyperalgesia in chronic pain.

    PubMed

    Severino, Amie; Chen, Wenling; Hakimian, Joshua K; Kieffer, Brigitte L; Gaveriaux-Ruff, Claire; Walwyn, Wendy; Marvizon, Juan Carlos

    2018-04-17

    The latent sensitization model of chronic pain reveals that recovery from some types of long-term hyperalgesia is an altered state in which nociceptive sensitization persists but is suppressed by the ongoing activity of analgesic receptors such as µ-opioid receptors (MORs). To determine whether these MORs are the ones present in nociceptive afferents, we bred mice expressing Cre-recombinase under the Nav1.8 channel promoter (Nav1.8cre) with MOR-floxed mice (flMOR). These Nav1.8cre/flMOR mice had reduced MOR expression in primary afferents, as revealed by quantitative PCR, in situ hybridization and immunofluorescence colocalization with the neuropeptide CGRP. We then studied the recovery from chronic pain of these mice and their flMOR littermates. When Nav1.8cre/flMOR mice were injected in the paw with complete Freund's adjuvant they developed mechanical hyperalgesia that persisted for over two months, whereas the responses of flMOR mice returned to baseline after three weeks. We then used the inverse agonist naltrexone to assess ongoing MOR activity. Naltrexone produced a robust reinstatement of hyperalgesia in control flMOR mice, but produced no effect in the Nav1.8/flMOR males and a weak reinstatement of hyperalgesia in Nav1.8/flMOR females. Naltrexone also reinstated swelling of the hind paw in flMOR mice and female Nav1.8cre/flMOR mice, but not male Nav1.8cre/flMOR mice. The MOR agonist DAMGO inhibited substance P release in flMOR mice but not Nav1.8cre/flMOR mice, demonstrating a loss of MOR function at the central terminals of primary afferents. We conclude that MORs in nociceptive afferents mediate an ongoing suppression of hyperalgesia to produce remission from chronic pain.

  4. Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson's disease.

    PubMed

    Lee, Kyung Duck; Koo, Jung Hoi; Song, Sun Hong; Jo, Kwang Deog; Lee, Moon Kyu; Jang, Wooyoung

    2015-11-01

    Dysphagia is an important issue in the prognosis of Parkinson's disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

  5. Spatial orientation of semicircular canals and afferent sensitivity vectors in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.

    1996-01-01

    Rotational head motion in vertebrates is detected by the semicircular canal system, whose innervating primary afferent fibers carry information about movement in specific head planes. The semicircular canals have been qualitatively examined over a number of years, and the canal planes have been quantitatively characterized in several animal species. The present study first determined the geometric relationship between individual semicircular canals and between the canals and the stereotactic head planes in pigeons. Stereotactic measurements of multiple points along the circumference of the bony canals were taken, and the measured points fitted with a three-dimensional planar surface. Direction normals to the plane's surface were calculated and used to define angles between semicircular canal pairs. Because of the unusual shape of the anterior semicircular canals in pigeons, two planes, a major and a minor, were fitted to the canal's course. Calculated angle values for all canals indicated that the horizontal and posterior semicircular canals are nearly orthogonal, but the anterior canals have substantial deviations from orthogonality with other canal planes. Next, the responses of the afferent fibers that innervate each of the semicircular canals to 0.5 Hz sinusoidal rotation about an earth-vertical axis were obtained. The head orientation relative to the rotation axis was systematically varied so that directions of maximum sensitivity for each canal afferent could be determined. These sensitivity vectors were then compared with the canal plane direction normals. The afferents that innervated specific semicircular canals formed homogeneous clusters of sensitivity vectors in different head planes. The horizontal and posterior afferents had average sensitivity vectors that were largely co-incident with the innervated canal plane direction normals. Anterior canal afferents, however, appeared to synthesize contributions from the major and minor plane components of the

  6. Vagal Afferent Innervation of the Airways in Health and Disease

    PubMed Central

    Mazzone, Stuart B.

    2016-01-01

    Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions. PMID:27279650

  7. Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats

    PubMed Central

    Kirkup, Anthony J; Jiang, Wen; Bunnett, Nigel W; Grundy, David

    2003-01-01

    Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001–1 mg kg−1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg−1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg−1, I.V.), but not a cocktail of ω-conotoxins GVIA and SVIB (each at 25 μg kg−1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg−1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms. PMID:14561839

  8. Enterocyte-afferent nerve interactions in dietary fat sensing.

    PubMed

    Mansouri, A; Langhans, W

    2014-09-01

    The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. © 2014 John Wiley & Sons Ltd.

  9. Resting afferent renal nerve discharge and renal inflammation: Elucidating the role of afferent and efferent renal nerves in DOCA-salt hypertension

    PubMed Central

    Banek, Christopher T.; Knuepfer, Mark M.; Foss, Jason D.; Fiege, Jessica K.; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W.

    2016-01-01

    Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity (RSNA) has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA)-salt rat model. Uninephrectomized male Sprague Dawley rats (275–300g) underwent selective afferent-selective RDNx (A-RDNx; n=10), total RDNx (T-RDNx; n=10), or Sham (n=10) and were instrumented for measurement of mean arterial pressure (MAP) and heart rate (HR) by radiotelemetry. Rats received 100mg DOCA (s.c.) and 0.9% saline for 21 days. Resting afferent renal nerve activity (ARNA) in DOCA and Vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting ARNA, expressed as a percent of peak afferent nerve activity (%Amax), was substantially increased in DOCA vs. Vehicle (35.8±4.4 vs. 15.3±2.8%Amax). The DOCA-Sham hypertension (132±12 mmHg) was attenuated by ~50% in both T-RDNx (111±8) and A-RDNx (117±5mmHg) groups. Renal inflammation induced by DOCA-salt was attenuated by T-RDNx, and unaffected by A-RDNx. These data suggest ARNA may mediate the hypertensive response to DOCA-salt, but inflammation may be mediated primarily by efferent RSNA. Also, resting ARNA is elevated in DOCA-salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. PMID:27698066

  10. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  11. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals

    PubMed Central

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S.; Kim, Hyeyoung; McRoberts, James A.; Marvizón, Juan Carlos G.

    2014-01-01

    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was mediated by tropomyosin-related kinase B (trkB) receptors and not p75 neurotrophin receptors (p75NTR), because it was not produced by proBDNF and was inhibited by the trkB antagonist ANA-12 but not by the p75NTR inhibitor TAT-Pep5. These effects are probably mediated through the truncated form of the trkB receptor as there is little expression of full-length trkB in dorsal root ganglion (DRG) neurons. Src family kinase inhibitors blocked the effect of BDNF, suggesting that trkB receptors promote the activation of these NMDA receptors by Src family kinase phosphorylation. Western blots of cultured DRG neurons revealed that BDNF increased Tyr1472 phosphorylation of the NR2B subunit of the NMDA receptor, known to have a potentiating effect. Patch-clamp recordings showed that BDNF, but not proBDNF, increased NMDA receptor currents in cultured DRG neurons. NMDA-induced NK1R internalization was also enabled in a neuropathic pain model or by activating dorsal horn microglia with lipopolysaccharide. These effects were decreased by a BDNF scavenger, a trkB receptor antagonist and an Src family kinase inhibitor, indicating that BDNF released by microglia potentiates NMDA receptors in primary afferents during neuropathic pain. PMID:24611998

  12. Directional tuning of human forearm muscle afferents during voluntary wrist movements

    PubMed Central

    Jones, Kelvin E; Wessberg, Johan; Vallbo, Åke B

    2001-01-01

    Single unit activity was recorded with the microneurography technique from sixteen spindle afferents and one Golgi tendon organ afferent originating from the forearm extensor muscles. Impulse rates were studied while subjects performed unobstructed aiming movements at the wrist in eight different directions 45 deg apart. In addition, similar imposed movements were performed while the subject was instructed to remain relaxed. Movement amplitudes were about 5 deg and the speed 10–30 deg s−1. Joint movements were translated to movements of a cursor on a monitor to provide visual feedback. Individual spindle afferents modulated their activity over a number of targets, i.e. were broadly tuned, during these aiming movements. The preferred direction for a spindle afferent was the same during both passive and active movements, indicating that the fusimotor effects associated with active contractions had little or no effect on the direction of tuning. The direction of tuning of individual spindle afferents could be predicted from the biomechanically inferred length changes of the parent muscle. Thus spindle afferents responded as stretch receptors, i.e. impulse rates increased with lengthening and decreased with shortening, in active as well as passive movements. Spindles from muscles, which continuously counteracted gravity exhibited a stretch response and directional tuning during the phase of movement alone whereas their position sensitivity was poor. In contrast, spindle afferents from the muscles that had no or minimal antigravity role were directionally tuned during both the dynamic and the static phase of the aiming task and their position sensitivity was substantially higher. In spite of the limited data base from three extensor muscles it could be demonstrated that wrist joint position was remarkably well encoded in the ensemble muscle spindle data. In some cases the ensemble muscle spindle data encoded the instantaneous trajectory of movement as well. PMID

  13. Parallel processing of afferent olfactory sensory information

    PubMed Central

    Vaaga, Christopher E.

    2016-01-01

    Key points The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood.One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation.Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons.Compared to external tufted cells, mitral cells have a prolonged afferent‐evoked EPSC, which serves to amplify the synaptic input.The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells.Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. Abstract Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1‐fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5‐fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic

  14. Establishing strategic alliance among hospitals through SAIS: a case study in Taiwan.

    PubMed

    Hung, Won-Fu; Hwang, Hsin-Ginn; Liao, Chechen

    2005-01-01

    Due to a reformed healthcare insurance system and a gradually decreasing public affairs' budget by the government year by year, Central Taiwan Office (CTO), the Department of Health (DOH) in Taiwan, initiated a strategic alliance project of the hospitals subordinated to the DOH in November, 2001. This project was a five-year plan with an attempt to expand and develop three more strategic alliances covering the northern, southern and eastern regions of Taiwan respectively. Through a cooperative system, such an alliance allows the following: resource sharing, technique collaboration, marketing affiliations and so on. In order to decrease operation management costs and improve the quality of service at hospitals, the strategic alliance practice is supported by IS. We call this alignment the IS-enabled strategic alliance. All the IS-enabled functions are supported by the Strategic Alliance Information System (SAIS). In this article, the SAIS developed by the CTO of the DOH is introduced.

  15. Central projections and entries of capsaicin-sensitive muscle afferents.

    PubMed

    Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

    1996-03-25

    The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

  16. Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles.

    PubMed

    Ikeda, Ryo; Gu, Jianguo

    2016-01-01

    Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when whisker hairs touch an object. The sensory signals are then conveyed by whisker afferent fibers to the brain for sensory perception. Electrophysiological property and chemical sensitivity of whisker afferent fibers, important factors affecting whisker sensory processing, are largely not known. In the present study, we performed patch-clamp recordings from pre-identified whisker afferent neurons in whole-mount trigeminal ganglion preparations and characterized their electrophysiological property and sensitivity to ATP, serotonin and glutamate. Of 97 whisker afferent neurons examined, 67% of them are found to be large-sized (diameter ≥45 µm) cells and 33% of them are medium- to small-sized (diameter <45 µm) cells. Almost every large-sized whisker afferent neuron fires a single action potential but many (40%) small/medium-sized whisker afferent neurons fire multiple action potentials in response to prolonged stepwise depolarization. Other electrophysiological properties including resting membrane potential, action potential threshold, and membrane input resistance are also significantly different between large-sized and small/medium-sized whisker afferent neurons. Most large-sized and many small/medium-sized whisker afferent neurons are sensitive to ATP and/or serotonin, and ATP and/or serotonin could evoke strong inward currents in these cells. In contrast, few whisker afferent neurons are sensitive to glutamate. Our results raise a possibility that ATP and/or serotonin may be chemical messengers involving sensory signaling for different types of rat whisker afferent fibers.

  17. Extinction in the Star Cluster SAI 113 and Galactic Structure in Carina

    NASA Astrophysics Data System (ADS)

    Carraro, Giovanni; Turner, David G.; Majaess, Daniel J.; Baume, Gustavo L.; Gamen, Roberto; Molina Lera, José A.

    2017-04-01

    Photometric CCD UB VI C photometry obtained for 4860 stars surrounding the embedded southern cluster SAI 113 (Skiff 8) is used to examine the reddening in the field and derive the distance to the cluster and nearby van Genderen 1. Spectroscopic color excesses for bright cluster stars, photometric reddenings for A3 dwarfs, and dereddening of cluster stars imply that the reddening and extinction laws match results derived for other young clusters in Carina: {E}U-B/{E}B-V≃ 0.64 and {R}V≃ 4. SAI 113 displays features that may be linked to a history of dynamical interactions among member stars: possible circumstellar reddening and rapid rotation of late B-type members, ringlike features in star density, and a compact core, with most stars distributed randomly across the field. The group van Genderen 1 resembles a stellar asterism, with potential members distributed randomly across the field. Distances of 3.90 ± 0.19 kpc and 2.49 ± 0.09 kpc are derived for SAI 113 and van Genderen 1, respectively, with variable reddenings {E}B-V ranging from 0.84 to 1.29 and 0.23 to 1.28. The SRC variables CK Car and EV Car may be outlying members of van Genderen 1, thereby of use for calibrating the period-luminosity relation for pulsating M supergiants. More importantly, the anomalous reddening and extinction evident in Carina and nearby regions of the Galactic plane in the fourth quadrant impact the mapping of spiral structure from young open clusters. The distribution of spiral arms in the fourth quadrant may be significantly different from how it is often portrayed.

  18. Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

    PubMed

    Caron, Guillaume; Decherchi, Patrick; Marqueste, Tanguy

    2015-09-01

    This study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent density…) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses.

  19. Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

    PubMed Central

    Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

    2008-01-01

    Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38

  20. The effect of vagal afferent on total vascular compliance in rats.

    PubMed

    Kinoshita, T

    1993-04-01

    This study was designed to investigate the effect of vagal afferent stimulation on total vascular compliance (TVC). Rats were anesthetized with sodium pentobarbital and artificially ventilated, TVC was determined together with stressed and unstressed blood volumes by measuring mean circulatory filling pressure (Pmcf) at three different levels of circulating blood volume. Measurements was repeated with the intact vagus, after vagotomy and during stimulation of vagal afferents. Vagotomy caused no change in TVC, Pmcf, and stressed and unstressed blood volumes. On the other hand, electrical stimulation of the vagal afferents for 30 sec increased TVC from 3.03 +/- 0.51 to 3.39 +/- 0.44 ml.mmHg(-1).kg(-1) (P < 0.05) and decreased Pmcf from 7.83 +/- 1.40 to 7.22 +/- 1.21 mmHg (P < 0.05). Neither stressed nor unstressed blood volume was changed by vagal stimulation. These results indicate that excitation of vagal afferent causes venodilation and increases TVC without changing stressed and unstressed blood volumes.

  1. Active touch and self-motion encoding by Merkel cell-associated afferents

    PubMed Central

    Severson, Kyle S.; Xu, Duo; Van de Loo, Margaret; Bai, Ling; Ginty, David D.; O’Connor, Daniel H.

    2017-01-01

    Summary Touch perception depends on integrating signals from multiple types of peripheral mechanoreceptors. Merkel-cell associated afferents are thought to play a major role in form perception by encoding surface features of touched objects. However, activity of Merkel afferents during active touch has not been directly measured. Here, we show that Merkel and unidentified slowly adapting afferents in the whisker system of behaving mice respond to both self-motion and active touch. Touch responses were dominated by sensitivity to bending moment (torque) at the base of the whisker and its rate of change, and largely explained by a simple mechanical model. Self-motion responses encoded whisker position within a whisk cycle (phase), not absolute whisker angle, and arose from stresses reflecting whisker inertia and activity of specific muscles. Thus, Merkel afferents send to the brain multiplexed information about whisker position and surface features, suggesting that proprioception and touch converge at the earliest neural level. PMID:28434802

  2. Transfer characteristics of the hair cell's afferent synapse

    NASA Astrophysics Data System (ADS)

    Keen, Erica C.; Hudspeth, A. J.

    2006-04-01

    The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

  3. Vibration-evoked reciprocal inhibition between human wrist muscles.

    PubMed

    Cody, F W; Plant, T

    1989-01-01

    Reciprocal inhibition of the voluntarily contracting wrist extensor (extensor carpi radialis, ECR) evoked by proprioceptive afferent input from the flexor (flexor carpi radialis, FCR), was studied in healthy human subjects. Vibration of the FCR tendon was used to elicit Ia-dominated afferent discharge whilst inhibition of ECR was assessed as the reduction in asynchronous, on-going EMG. A small early phase of inhibition (I1) was evident in 25% of trials. The latency (ca. 25 ms) of this component suggested that it was mediated by an Ia oligosynaptic. possibly 'classical' disynaptic, inhibitory pathway. A later and apparently separate phase of reduced activity (I2, ca. 40 ms) was, however, far more consistently observed (96% of trials) and of greater magnitude. The I2 component was usually followed, some 20 ms later, by a phase of elevated activity (E1, 72% trials). Reductions in simultaneously recorded net extensor torque commenced at about 60 ms following the onset of flexor tendon vibration, i.e. some 20 ms after the main I2 EMG component. These mechanical responses must have almost exclusively resulted from reciprocal inhibition of extensor EMG since vibration of the relaxed FCR evoked minimal excitatory flexor activity. The reflex pattern, in any individual subject, was relatively unaffected by altering the duration of the vibration train between one and nineteen cycles (125 Hz). This suggests that the entire response complex resulted largely from the initial afferent volley. The sizes of both the I1 and I2 reductions in ECR activity increased with increasing voluntary extensor contraction so that their depths remained constant proportions of background EMG. Very similar results were obtained when reciprocal inhibition of FCR was produced by vibration of the belly of ECR. Thus, reciprocal inhibition between wrist muscles is mainly expressed as a rather stereotyped, short duration reduction in EMG whose depth is determined by the pre-existing level of motor

  4. Changes in monkey horizontal semicircular canal afferent responses after spaceflight

    NASA Technical Reports Server (NTRS)

    Correia, M. J.; Perachio, A. A.; Dickman, J. D.; Kozlovskaia, I. B.; Sirota, M. G.; Iakushin, S. B.; Beloozerova, I. N.

    1992-01-01

    Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (Cosmos 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

  5. Gut vagal afferents differentially modulate innate anxiety and learned fear.

    PubMed

    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

    2014-05-21

    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

  6. Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells.

    PubMed

    Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco

    2011-02-01

    Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

  7. Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia.

    PubMed

    Benussi, Alberto; Di Lorenzo, Francesco; Dell'Era, Valentina; Cosseddu, Maura; Alberici, Antonella; Caratozzolo, Salvatore; Cotelli, Maria Sofia; Micheli, Anna; Rozzini, Luca; Depari, Alessandro; Flammini, Alessandra; Ponzo, Viviana; Martorana, Alessandro; Caltagirone, Carlo; Padovani, Alessandro; Koch, Giacomo; Borroni, Barbara

    2017-08-15

    To determine whether a transcranial magnetic stimulation (TMS) multiparadigm approach can be used to distinguish Alzheimer disease (AD) from frontotemporal dementia (FTD). Paired-pulse TMS was used to investigate short-interval intracortical inhibition (SICI) and facilitation (ICF), long-interval intracortical inhibition, and short-latency afferent inhibition (SAI) to measure the activity of different intracortical circuits in patients with AD, patients with FTD, and healthy controls (HC). The primary outcome measures were sensitivity and specificity of TMS measures, derived from receiver operating curve analysis. A total of 175 participants met the inclusion criteria. We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that while patients with AD are characterized by a specific impairment of SAI, FTD shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8% and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%. These results were confirmed in patients with mild disease. TMS is a noninvasive procedure that reliably distinguishes AD from FTD and HC and, if these findings are replicated in larger studies, could represent a useful additional diagnostic tool for clinical practice. This study provides Class III evidence that TMS measures can distinguish patients with AD from those with FTD. © 2017 American Academy of Neurology.

  8. A bioinspired flexible organic artificial afferent nerve

    NASA Astrophysics Data System (ADS)

    Kim, Yeongin; Chortos, Alex; Xu, Wentao; Liu, Yuxin; Oh, Jin Young; Son, Donghee; Kang, Jiheong; Foudeh, Amir M.; Zhu, Chenxin; Lee, Yeongjun; Niu, Simiao; Liu, Jia; Pfattner, Raphael; Bao, Zhenan; Lee, Tae-Woo

    2018-06-01

    The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.

  9. Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects

    PubMed Central

    2016-01-01

    The central terminals of primary afferent fibers experience depolarization upon activation of GABAA receptors (GABAAR) because their intracellular chloride concentration is maintained above electrochemical equilibrium. Primary afferent depolarization (PAD) normally mediates inhibition via sodium channel inactivation and shunting but can evoke spikes under certain conditions. Antidromic (centrifugal) conduction of these spikes may contribute to neurogenic inflammation while orthodromic (centripetal) conduction could contribute to pain in the case of nociceptive fibers. PAD-induced spiking is assumed to override presynaptic inhibition. Using computer simulations and dynamic clamp experiments, we sought to identify which biophysical changes are required to enable PAD-induced spiking and whether those changes necessarily compromise PAD-mediated inhibition. According to computational modeling, a depolarizing shift in GABA reversal potential (EGABA) and increased intrinsic excitability (manifest as altered spike initiation properties) were necessary for PAD-induced spiking, whereas increased GABAAR conductance density (ḡGABA) had mixed effects. We tested our predictions experimentally by using dynamic clamp to insert virtual GABAAR conductances with different EGABA and kinetics into acutely dissociated dorsal root ganglion (DRG) neuron somata. Comparable experiments in central axon terminals are prohibitively difficult but the biophysical requirements for PAD-induced spiking are arguably similar in soma and axon. Neurons from naïve (i.e. uninjured) rats were compared before and after pharmacological manipulation of intrinsic excitability, and against neurons from nerve-injured rats. Experimental data confirmed that, in most neurons, both predicted changes were necessary to yield PAD-induced spiking. Importantly, such changes did not prevent PAD from inhibiting other spiking or from blocking spike propagation. In fact, since the high value of ḡGABA required for PAD

  10. Effects from fine muscle and cutaneous afferents on spinal locomotion in cats

    PubMed Central

    Kniffki, K.-D.; Schomburg, E. D.; Steffens, H.

    1981-01-01

    1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l-DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi- and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar α-motoneurones. 2. After nialamide but before treatment with l-DOPA, in some cases, transient locomotor-like discharges were induced by an increased activity in fine muscle afferents. The response pattern in nerves to both hind limbs could be different showing e.g. only transient alternating activity between knee flexor and extensor of one limb but not of the other one. 3. Treatment with l-DOPA did not always cause fictive locomotion. Often not all motoneurone pools showed rhythmic activity. In these cases stimulation of group III and IV muscle afferents usually caused transient periodic activity. In cases with apparent rhythmic activity, algesic stimulation of the gastrocnemius—soleus muscle caused an accentuation of the rhythm by a more abrupt transition from the active phase to the non-active interval. Again, the response patterns on both sides were not uniform in all cases. 4. A second type of response to activation of fine muscle afferents had a quite different character: the rhythmic activity was more or less completely overridden by a strong transient tonic hyperactivity or the rhythm was transiently blocked. These phenomena did not occur in the same way in all nerves. 5. Electrical stimulation of cutaneous nerves of the hind limb generally induced the same response pattern as chemical stimulation of the group III and IV muscle afferents. The effects varied depending on the stimulus strength and the nerve. 6. The results revealed that cutaneous and fine muscle afferents not only

  11. Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

    PubMed Central

    Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

    2017-01-01

    Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

  12. Tonic Investigation Concept of Cervico-vestibular Muscle Afferents

    PubMed Central

    Dorn, Linda Josephine; Lappat, Annabelle; Neuhuber, Winfried; Scherer, Hans; Olze, Heidi; Hölzl, Matthias

    2016-01-01

    Introduction Interdisciplinary research has contributed greatly to an improved understanding of the vestibular system. To date, however, very little research has focused on the vestibular system's somatosensory afferents. To ensure the diagnostic quality of vestibular somatosensory afferent data, especially the extra cranial afferents, stimulation of the vestibular balance system has to be precluded. Objective Sophisticated movements require intra- and extra cranial vestibular receptors. The study's objective is to evaluate an investigation concept for cervico-vestibular afferents with respect to clinical feasibility. Methods A dedicated chair was constructed, permitting three-dimensional trunk excursions, during which the volunteer's head remains fixed. Whether or not a cervicotonic provocation nystagmus (c-PN) can be induced with static trunk excursion is to be evaluated and if this can be influenced by cervical monophasic transcutaneous electrical nerve stimulation (c-TENS) with a randomized test group. 3D-video-oculography (VOG) was used to record any change in cervico-ocular examination parameters. The occurring nystagmuses were evaluated visually due to the small caliber of nystagmus amplitudes in healthy volunteers. Results The results demonstrate: no influence of placebo-controlled c-TENS on the spontaneous nystagmus; a significant increase of the vertical nystagmus on the 3D-trunk-excursion chair in static trunk flexion with cervical provocation in all young healthy volunteers (n = 49); and a significant difference between vertical and horizontal nystagmuses during static trunk excursion after placebo-controlled c-TENS, except for the horizontal nystagmus during trunk torsion. Conclusion We hope this cervicotonic investigation concept on the 3D trunk-excursion chair will contribute to new diagnostic and therapeutic perspectives on cervical pathologies in vestibular head-to-trunk alignment. PMID:28050208

  13. Information analysis of posterior canal afferents in the turtle, Trachemys scripta elegans.

    PubMed

    Rowe, Michael H; Neiman, Alexander B

    2012-01-24

    We have used sinusoidal and band-limited Gaussian noise stimuli along with information measures to characterize the linear and non-linear responses of morpho-physiologically identified posterior canal (PC) afferents and to examine the relationship between mutual information rate and other physiological parameters. Our major findings are: 1) spike generation in most PC afferents is effectively a stochastic renewal process, and spontaneous discharges are fully characterized by their first order statistics; 2) a regular discharge, as measured by normalized coefficient of variation (cv*), reduces intrinsic noise in afferent discharges at frequencies below the mean firing rate; 3) coherence and mutual information rates, calculated from responses to band-limited Gaussian noise, are jointly determined by gain and intrinsic noise (discharge regularity), the two major determinants of signal to noise ratio in the afferent response; 4) measures of optimal non-linear encoding were only moderately greater than optimal linear encoding, indicating that linear stimulus encoding is limited primarily by internal noise rather than by non-linearities; and 5) a leaky integrate and fire model reproduces these results and supports the suggestion that the combination of high discharge regularity and high discharge rates serves to extend the linear encoding range of afferents to higher frequencies. These results provide a framework for future assessments of afferent encoding of signals generated during natural head movements and for comparison with coding strategies used by other sensory systems. This article is part of a Special Issue entitled: Neural Coding. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

    PubMed Central

    Li, Jie

    2017-01-01

    It is well established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared with skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared with pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn neurons process sensory input from muscle versus skin at the synaptic level. Using a novel ex vivo spinal cord preparation, here we identify the functional organization of muscle and cutaneous afferent synapses onto immature rat lamina I spino-parabrachial neurons, which serve as a major source of nociceptive transmission to the brain. Stimulation of the gastrocnemius nerve and sural nerve revealed significant convergence of muscle and cutaneous afferent synaptic input onto individual projection neurons. Muscle afferents displayed a higher probability of glutamate release, although short-term synaptic plasticity was similar between the groups. Importantly, muscle afferent synapses exhibited greater relative expression of Ca2+-permeable AMPARs compared with cutaneous inputs. In addition, the prevalence and magnitude of spike timing-dependent long-term potentiation were significantly higher at muscle afferent synapses, where it required Ca2+-permeable AMPAR activation. Collectively, these results provide the first evidence for afferent-specific properties of glutamatergic transmission within the superficial dorsal horn. A larger propensity for activity-dependent strengthening at muscle afferent synapses onto developing spinal projection neurons could contribute to the enhanced ability of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain in children following injury. SIGNIFICANCE STATEMENT The neurobiological mechanisms underlying the high prevalence of chronic

  15. Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.

    PubMed

    Aizawa, Naoki; Wakamatsu, Daisuke; Kida, Jun; Otsuki, Takeya; Saito, Yasuho; Matsuya, Hidekazu; Homma, Yukio; Igawa, Yasuhiko

    2017-02-01

    Kv7 voltage-gated potassium channels have been suggested to modulate mechano-afferent transduction and nociception in the bladder. We investigated the effects of retigabine, a Kv7 channel activator, on rhythmic bladder contractions (RBCs), and single-unit afferent activities (SAAs) of the primary bladder mechanosensitive afferent nerve fibers in urethane-anesthetized rats. In addition, the effects of pretreatment with retigabine on the nociceptive behaviors provoked by an intravesical instillation of resiniferatoxin (RTX) were evaluated in the conscious condition. Female Sprague-Dawley rats were used. Under urethane anesthesia, saline was instilled into the bladder until RBCs were induced reproducibly. Then, the effects of intravenous, cumulative administrations of retigabine (0.1-3 mg/kg) or vehicle (saline) on RBCs were assessed. In separate animals, SAAs of Aδ- and C-fibers were identified by electrical stimulation of the pelvic nerve and by bladder distention with saline. After baseline recording, vehicle or retigabine (0.01-1 mg/kg) was administered intravenously and further recordings were performed. Under pretreatment with vehicle or retigabine (3 mg/kg intraperitoneally), the frequencies of lower abdominal licking and freezing were counted and scored as the bladder nociceptive behaviors induced by intravesical RTX instillation (3 µM, 0.3 ml). Retigabine dose-dependently decreased both the frequency and the amplitude of RBCs and SAAs of both Aδ- and C-fibers. The effect on RBCs was more potent on the frequency than the amplitude. Retigabine inhibited the RTX-induced abdominal licking, but not freezing. Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  16. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    PubMed

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

  17. First-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer : analysis of the Italian patients enrolled in the SAiL study.

    PubMed

    Bearz, Alessandra; Passalacqua, Rodolfo; Alabiso, Oscar; Cinieri, Saverio; Gridelli, Cesare; Cravesana, Claudia; Crinò, Lucio

    2012-11-01

    First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more

  18. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

    PubMed

    Egerod, Kristoffer L; Petersen, Natalia; Timshel, Pascal N; Rekling, Jens C; Wang, Yibing; Liu, Qinghua; Schwartz, Thue W; Gautron, Laurent

    2018-06-01

    G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Na v 1.8-expressing afferents. GPCRs for gut hormones that were the most enriched in Na v 1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Na v 1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Na v 1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  19. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

    PubMed

    Leung, Felix W

    2008-07-04

    This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

  20. Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

    PubMed Central

    Chagas, André M.; Theis, Lucas; Sengupta, Biswa; Stüttgen, Maik C.; Bethge, Matthias; Schwarz, Cornelius

    2013-01-01

    Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of “how much” information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on “what” is coded by primary afferents. Amongst the kinematic variables tested—position, velocity, and acceleration—primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80–90%. The final 10–20% were found to be due to non-linear coding by spike bursts. PMID:24367295

  1. Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

    PubMed

    Ro, J Y; Capra, N F

    2001-05-01

    Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

  2. Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function.

    PubMed

    Liu, Yang; Wu, Di; Qu, Mei-Yu; He, Jian-Li; Yuan, Mei; Zhao, Miao; Wang, Jian-Xin; He, Jian; Wang, Lu-Qi; Guo, Xin-Jing; Zuo, Meng; Zhao, Shu-Yang; Ma, Mei-Na; Li, Jun-Nan; Shou, Weinian; Qiao, Guo-Fen; Li, Bai-Yan

    2016-10-04

    Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y1R, not Y2R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y1R and Y2R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y1R expression/distribution was identical between A- and C-types, whereas, expressed level of Y2R was ~15 and ~7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y1R in nodose elevated BP, while activation of Y2R did the opposite. Activation of Y1R did not alter action potential duration (APD) of A-types, but activation of Y2R- and Y1R/Y2R in Ah- and C-types frequency-dependently prolonged APD. N-type ICa was reduced in A-, Ah- and C-types when either Y1R, Y2R, or both were activated. The sex-difference in Y1R expression was also observed in NTS. Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation.

  3. The pebbles/boulders size distributions on Sais: Rosetta's final landing site on comet 67P/Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Pajola, M.; Lucchetti, A.; Fulle, M.; Mottola, S.; Hamm, M.; Da Deppo, V.; Penasa, L.; Kovacs, G.; Massironi, M.; Shi, X.; Tubiana, C.; Güttler, C.; Oklay, N.; Vincent, J. B.; Toth, I.; Davidsson, B.; Naletto, G.; Sierks, H.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; Keller, H. U.; Agarwal, J.; A'Hearn, M. F.; Barucci, M. A.; Bertaux, J. L.; Bertini, I.; Cremonese, G.; Debei, S.; De Cecco, M.; Deller, J.; El Maarry, M. R.; Fornasier, S.; Frattin, E.; Gicquel, A.; Groussin, O.; Gutierrez, P. J.; Höfner, S.; Hofmann, M.; Hviid, S. F.; Ip, W. H.; Jorda, L.; Knollenberg, J.; Kramm, J. R.; Kührt, E.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Moreno, J. J. Lopez; Marzari, F.; Michalik, H.; Preusker, F.; Scholten, F.; Thomas, N.

    2017-07-01

    By using the imagery acquired by the Optical, Spectroscopic, and Infrared Remote Imaging System Wide-Angle Camera (OSIRIS WAC), we prepare a high-resolution morphological map of the Rosetta Sais final landing site, characterized by an outcropping consolidated terrain unit, a coarse boulder deposit and a fine particle deposit. Thanks to the 0.014 m resolution images, we derive the pebbles/boulders size-frequency distribution (SFD) of the area in the size range of 0.07-0.70 m. Sais' SFD is best fitted with a two-segment differential power law: the first segment is in the range 0.07-0.26 m, with an index of -1.7 ± 0.1, while the second is in the range 0.26-0.50 m, with an index of -4.2 +0.4/-0.8. The `knee' of the SFD, located at 0.26 m, is evident both in the coarse and fine deposits. When compared to the Agilkia Rosetta Lander Imaging System images, Sais surface is almost entirely free of the ubiquitous, cm-sized debris blanket observed by Philae. None the less, a similar SFD behaviour of Agilkia, with a steeper distribution above ˜0.3 m, and a flatter trend below that, is observed. The activity evolution of 67P along its orbit provides a coherent scenario of how these deposits were formed. Indeed, different lift pressure values occurring on the two locations and at different heliocentric distances explain the presence of the cm-sized debris blanket on Agilkia observed at 3.0 au inbound. Contrarily, Sais activity after 2.1 au outbound has almost completely eroded the fine deposits fallen during perihelion, resulting in an almost dust-free surface observed at 3.8 au.

  4. Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

    PubMed Central

    Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

    2004-01-01

    We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

  5. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    PubMed

    Dimitriou, Michael

    2016-04-25

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Putative roles of neuropeptides in vagal afferent signaling

    PubMed Central

    de Lartigue, Guillaume

    2014-01-01

    The vagus nerve is a major pathway by which information is communicated between the brain and peripheral organs. Sensory neurons of the vagus are located in the nodose ganglia. These vagal afferent neurons innervate the heart, the lung and the gastrointestinal tract, and convey information about peripheral signals to the brain important in the control of cardiovascular tone, respiratory tone, and satiation, respectively. Glutamate is thought to be the primary neurotransmitter involved in conveying all of this information to the brain. It remains unclear how a single neurotransmitter can regulate such an extensive list of physiological functions from a wide range of visceral sites. Many neurotransmitters have been identified in vagal afferent neurons and have been suggested to modulate the physiological functions of glutamate. Specifically, the anorectic peptide transmitters, cocaine and amphetamine regulated transcript (CART) and the orexigenic peptide transmitters, melanin concentrating hormone (MCH) are differentially regulated in vagal afferent neurons and have opposing effects on food intake. Using these two peptides as a model, this review will discuss the potential role of peptide transmitters in providing a more precise and refined modulatory control of the broad physiological functions of glutamate, especially in relation to the control of feeding. PMID:24650553

  7. NREL, Johns Hopkins SAIS Develop Method to Quantify Life Cycle Land Use of

    Science.gov Websites

    Life Cycle Land Use of Electricity from Natural Gas News Release: NREL, Johns Hopkins SAIS Develop Method to Quantify Life Cycle Land Use of Electricity from Natural Gas October 2, 2017 A case study of time provides quantifiable information on the life cycle land use of generating electricity from

  8. Activation of normal and inflamed fine articular afferent units by serotonin.

    PubMed

    Herbert, M K; Schmidt, R F

    1992-07-01

    In cats anesthetized with alpha-chloralose, extracellular recordings were made from fine afferent units belonging to the medial articular nerve (MAN) of the knee joint. The excitatory and sensitizing effects on articular afferents of serotonin (5-HT) applied intra-arterially close to the joint were examined. The joints were either normal or an experimental arthritis had been induced some hours before the recording session. Bolus injections of 1.35-135 micrograms 5-HT excited about 43% of group III (CV: 2.5-20 m/sec) and 73% of group IV units (CV: less than 2.5 m/sec) from normal joints. The latency was usually between 10 and 30 sec, and the duration and size of the responses were dose-dependent. Fast group III units (CV: greater than 16 m/sec) and group II units (CV: greater than 20 m/sec) were never excited by 5-HT. Repetitive administration led to pronounced tachyphylaxis of the 5-HT response. Inflammation induced an enhanced sensitivity of group III articular afferent units to close intra-arterial application of 5-HT. In particular the total duration of each response was considerably prolonged (4-10 min against 1-2 min under normal conditions). At the same time the tachyphylaxis seen under normal conditions was greatly reduced. In contrast, group IV articular afferent units did not become sensitized to 5-HT in the course of inflammation. In normal joints 5-HT did not sensitize fine afferent units for movement-induced responses. However, after inflammation, a distinct sensitization to such movements by 5-HT application could be observed both in group III and group IV fiber ranges. The sensitization had a short time course not exceeding 7 min. The tonic component of the movement-induced response was more enhanced than the phasic one. The bolus application of 5-HT led to temporary vasoconstriction of the knee joint vessels. This vasoconstriction was especially pronounced in inflamed joints and impeded the access of subsequently applied substances to the terminal

  9. Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles

    PubMed Central

    Laine, Christopher M.; Valero-Cuevas, Francisco J.

    2018-01-01

    Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,‘common drive’), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary ‘isometric’ force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease. PMID:29309405

  10. Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles.

    PubMed

    Nagamori, Akira; Laine, Christopher M; Valero-Cuevas, Francisco J

    2018-01-01

    Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,'common drive'), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary 'isometric' force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease.

  11. Laryngeal and tracheal afferent nerve stimulation evokes swallowing in anaesthetized guinea pigs

    PubMed Central

    Tsujimura, Takanori; Udemgba, Chioma; Inoue, Makoto; Canning, Brendan J

    2013-01-01

    We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by laryngeal citric acid challenges were abolished by recurrent laryngeal nerve (RLN) transection and mimicked by electrical stimulation of the central cut ends of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal distensions was not significantly reduced by RLN transection but they were virtually abolished by superior laryngeal nerve transection. Laryngeal citric acid-evoked swallowing was mimicked by laryngeal capsaicin challenges, implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal afferent nerves arising from the jugular ganglia. The swallowing evoked by citric acid and capsaicin and evoked by electrical stimulation of either the tracheal or the laryngeal mucosa occurred at stimulation intensities that were typically subthreshold for evoking cough in these animals. Swallowing evoked by airway afferent nerve stimulation also desensitized at a much slower rate than cough. We speculate that swallowing is an essential component of airway protection from aspiration associated with laryngeal and tracheal afferent nerve activation. PMID:23858010

  12. Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

    PubMed

    Yavuz, Utku Ş; Negro, Francesco; Diedrichs, Robin; Farina, Dario

    2018-05-01

    Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted

  13. Acute cholangitis due to afferent loop syndrome after a Whipple procedure: a case report.

    PubMed

    Spiliotis, John; Karnabatidis, Demetrios; Vaxevanidou, Archodoula; Datsis, Anastasios C; Rogdakis, Athanasios; Zacharis, Georgios; Siamblis, Demetrios

    2009-08-25

    Patients with resection of stomach and especially with Billroth II reconstruction (gastro jejunal anastomosis), are more likely to develop afferent loop syndrome which is a rare complication. When the afferent part is obstructed, biliary and pancreatic secretions accumulate and cause the distention of this part. In the case of a complete obstruction (rare), there is a high risk developing necrosis and perforation. This complication has been reported once in the literature. A 54-year-old Greek male had undergone a pancreato-duodenectomy (Whipple procedure) one year earlier due to a pancreatic adenocarcinoma. Approximately 10 months after the initial operation, the patient started having episodes of cholangitis (fever, jaundice) and abdominal pain. This condition progressively worsened and the suspicion of local recurrence or stenosis of the biliary-jejunal anastomosis was discussed. A few days before his admission the patient developed signs of septic cholangitis. Our case demonstrates a rare complication with serious clinical manifestation of the afferent loop syndrome. This advanced form of afferent loop syndrome led to the development of huge enterobiliary reflux, which had a serious clinical manifestation as cholangitis and systemic sepsis, due to bacterial overgrowth, which usually present in the afferent loop. The diagnosis is difficult and the interventional radiology gives all the details to support the therapeutic decision making. A variety of factors can contribute to its development including adhesions, kinking and angulation of the loop, stenosis of gastro-jejunal anastomosis and internal herniation. In order to decompress the afferent loop dilatation due to adhesions, a lateral-lateral jejunal anastomosis was performed between the afferent loop and a small bowel loop.

  14. Subcortical afferent connections of the amygdala in the monkey

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1980-01-01

    The cells of origin of the afferent connections of the amygdala in the rhesus and squirrel monkeys are determined according to the retrograde axonal transport of the enzyme horseradish peroxidase injected into various quadrants of the amygdala. Analysis of the distribution of enzyme-labeled cells reveals afferent amygdalar connections with the ipsilateral halves of the midline nucleus paraventricularis thalami and both the parvo- and magnocellular parts of the nucleus subparafascicularis in the dorsal thalamus, all the subdivisions of the midline nucleus centralis complex, the nucleus reuniens ventralis and the nucleus interventralis. The largest populations of enzyme-labeled cells in the hypothalamus are found to lie in the middle and posterior parts of the ipsilateral, lateral hypothalamus and the ventromedial hypothalamic nucleus, with scattered cells in the supramammillary and dorsomedial nuclei and the posterior hypothalamic area, Tsai's ventral tegmental area, the rostral and caudal subdivisions of the nucleus linearis in the midbrain and the dorsal raphe nucleus. The most conspicuous subdiencephalic source of amygdalar afferent connections is observed to be the pars lateralis of the nucleus parabrachialis in the dorsolateral pontine tegmentum, with a few labeled cells differentiated from pigmented cells in the locus coeruleus.

  15. Effects of stimulation of muscarinic receptors on bladder afferent nerves in the in vitro bladder-pelvic afferent nerve preparation of the rat.

    PubMed

    Yu, Yongbei; de Groat, William C

    2010-11-18

    Effects of a muscarinic receptor agonist oxotremorine-M (oxo-M) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced rhythmic bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 25 and 50 μM oxo-M significantly increased afferent firing from 41 ± 2 spikes/s to 51 ± 4 spikes/s and 60.5 ± 5 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. The afferent nerve firing induced by isotonic distension of the bladder (10-40 cmH(2)O) was increased 22-100% by intravesical administration of 50 μM oxo-M. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Oxo-M significantly decreased the voltage threshold by 40% (p<0.05) and increased by 157% (p<0.05) the area of the AP evoked at a submaximal stimulus intensity. These effects were blocked by intravesical injection of 5 μM atropine methyl nitrate (AMN). Intravesical administration of 5 μM AMN alone did not alter BAN firing or the amplitude of bladder contractions. The facilitatory effects induced by oxo-M on BAN activity were also suppressed (p<0.05) by intravesical administration of 2',3'-0-trinitrophenyl-ATP (TNP-ATP) (30 μM). In preparations pretreated with capsaicin (125 mg/kg, s.c.) the facilitatory effects of 50 μM oxo-M on BAN activity were absent. These results suggest that activation of muscarinic receptors facilitates mechano-sensitive, capsaicin-sensitive BAN activity in part by mechanisms involving purinergic receptors located near the luminal surface of the bladder and ATP release which presumably occurs in the urothelium. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. The Bayesian Decoding of Force Stimuli from Slowly Adapting Type I Fibers in Humans.

    PubMed

    Kasi, Patrick; Wright, James; Khamis, Heba; Birznieks, Ingvars; van Schaik, André

    2016-01-01

    It is well known that signals encoded by mechanoreceptors facilitate precise object manipulation in humans. It is therefore of interest to study signals encoded by the mechanoreceptors because this will contribute further towards the understanding of fundamental sensory mechanisms that are responsible for coordinating force components during object manipulation. From a practical point of view, this may suggest strategies for designing sensory-controlled biomedical devices and robotic manipulators. We use a two-stage nonlinear decoding paradigm to reconstruct the force stimulus given signals from slowly adapting type one (SA-I) tactile afferents. First, we describe a nonhomogeneous Poisson encoding model which is a function of the force stimulus and the force's rate of change. In the decoding phase, we use a recursive nonlinear Bayesian filter to reconstruct the force profile, given the SA-I spike patterns and parameters described by the encoding model. Under the current encoding model, the mode ratio of force to its derivative is: 1.26 to 1.02. This indicates that the force derivative contributes significantly to the rate of change to the SA-I afferent spike modulation. Furthermore, using recursive Bayesian decoding algorithms is advantageous because it can incorporate past and current information in order to make predictions--consistent with neural systems--with little computational resources. This makes it suitable for interfacing with prostheses.

  17. The Bayesian Decoding of Force Stimuli from Slowly Adapting Type I Fibers in Humans

    PubMed Central

    Wright, James; Khamis, Heba; Birznieks, Ingvars; van Schaik, André

    2016-01-01

    It is well known that signals encoded by mechanoreceptors facilitate precise object manipulation in humans. It is therefore of interest to study signals encoded by the mechanoreceptors because this will contribute further towards the understanding of fundamental sensory mechanisms that are responsible for coordinating force components during object manipulation. From a practical point of view, this may suggest strategies for designing sensory-controlled biomedical devices and robotic manipulators. We use a two-stage nonlinear decoding paradigm to reconstruct the force stimulus given signals from slowly adapting type one (SA-I) tactile afferents. First, we describe a nonhomogeneous Poisson encoding model which is a function of the force stimulus and the force’s rate of change. In the decoding phase, we use a recursive nonlinear Bayesian filter to reconstruct the force profile, given the SA-I spike patterns and parameters described by the encoding model. Under the current encoding model, the mode ratio of force to its derivative is: 1.26 to 1.02. This indicates that the force derivative contributes significantly to the rate of change to the SA-I afferent spike modulation. Furthermore, using recursive Bayesian decoding algorithms is advantageous because it can incorporate past and current information in order to make predictions—consistent with neural systems—with little computational resources. This makes it suitable for interfacing with prostheses. PMID:27077750

  18. Tempol prevents altered K(+) channel regulation of afferent arteriolar tone in diabetic rat kidney.

    PubMed

    Troncoso Brindeiro, Carmen M; Lane, Pascale H; Carmines, Pamela K

    2012-03-01

    Experiments were performed to test the hypothesis that oxidative stress underlies the enhanced tonic dilator impact of inward-rectifier K(+) channels on renal afferent arterioles of rats with streptozotocin-induced diabetes mellitus. Sham and diabetic rats were left untreated or provided Tempol in their drinking water for 26±1 days, after which afferent arteriolar lumen diameter and its responsiveness to K(+) channel blockade were measured using the in vitro blood-perfused juxtamedullary nephron technique. Afferent diameter averaged 19.4±0.8 μm in sham rats and 24.4±0.8 μm in diabetic rats (P<0.05). The decrease in diameter evoked by Ba(2+) (inward-rectifier K(+) channel blocker) was 3 times greater in diabetic rats than in sham rats. Glibenclamide (K(ATP) channel blocker) and tertiapin-Q (Kir1.1/Kir3.x channel blocker) decreased afferent diameter in diabetic rats but had no effect on arterioles from sham rats. Chronic Tempol treatment prevented diabetes mellitus-induced increases in both renal vascular dihydroethidium staining and baseline afferent arteriolar diameter. Moreover, Tempol prevented the exaggeration of afferent arteriolar responses to Ba(2+), tertiapin-Q, and glibenclamide otherwise evident in diabetic rats. Preglomerular microvascular smooth muscle cells expressed mRNA encoding Kir1.1, Kir2.1, and Kir6.1. Neither diabetes mellitus nor Tempol altered Kir1.1, Kir2.1, Kir6.1, or SUR2B protein levels in renal cortical microvessels. To the extent that the effects of Tempol reflect its antioxidant actions, our observations indicate that oxidative stress contributes to the exaggerated impact of Kir1.1, Kir2.1, and K(ATP) channels on afferent arteriolar tone during diabetes mellitus and that this phenomenon involves posttranslational modulation of channel function.

  19. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

    PubMed

    Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

    2013-10-15

    Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

  20. Implications for bidirectional signaling between afferent nerves and urothelial cells-ICI-RS 2014.

    PubMed

    Kanai, Anthony; Fry, Christopher; Ikeda, Youko; Kullmann, Florenta Aura; Parsons, Brian; Birder, Lori

    2016-02-01

    To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed. It is clear that afferent-urothelial interactions are integral to the regulation of normal bladder function and that its disruption can have detrimental consequences. The urothelium is capable of releasing numerous signaling factors that can affect sensory neurons innervating the suburothelium. However, the understanding of how factors released from urothelial cells and afferent nerve terminals regulate one another is incomplete. Utilization of techniques such as viruses that genetically encode Ca(2+) sensors, based on calmodulin and green fluorescent protein, has helped to address the cellular mechanisms involved. Additionally, the epithelial-neuronal interactions in the urethra may also play a significant role in lower urinary tract regulation and merit further investigation. The signaling capabilities of the urothelium and afferent nerves are well documented, yet how these signals are integrated to regulate bladder function is unclear. There is unquestionably a need for expanded methodologies to further our understanding of lower urinary tract sensory mechanisms and their contribution to various pathologies. © 2016 Wiley Periodicals, Inc.

  1. Role of eicosanoids, nitric oxide, and afferent neurons in antacid induced protection in the rat stomach.

    PubMed Central

    Lambrecht, N; Trautmann, M; Korolkiewicz, R; Liszkay, M; Peskar, B M

    1993-01-01

    The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti-inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity. PMID:8472979

  2. Low- and high-threshold primary afferent inputs to spinal lamina III antenna-type neurons.

    PubMed

    Fernandes, Elisabete C; Santos, Ines C; Kokai, Eva; Luz, Liliana L; Szucs, Peter; Safronov, Boris V

    2018-06-21

    and non-nociceptive sensory information. Antenna-type neurons with cell bodies located in lamina III and large dendritic trees extending from the superficial lamina I to deep lamina IV are best shaped for the integration of a wide variety of inputs arising from primary afferent fibers and intrinsic spinal circuitries. While the somatodendritic morphology, the hallmark of antenna neurons, has been well studied, little is still known about the axon structure and basic physiological properties of these cells. Here we did whole-cell recordings in a rat (P9-P12) spinal cord preparation with attached dorsal roots to examine the axon course, intrinsic firing properties and primary afferent inputs of antenna cells. Nine antenna cells were identified from a large sample of biocytin-filled lamina III neurons (n = 46). Axon of antenna cells showed intensive branching in laminae III-IV and, in half of the cases, issued dorsally directed collaterals reaching lamina I. Antenna cells exhibited tonic and rhythmic firing patterns; single spikes were followed by hyper- or depolarization. The neurons received monosynaptic inputs from the low-threshold Aβ afferents, Aδ afferents as well as from the high-threshold Aδ and C afferents. When selectively activated, C-fiber-driven mono- and polysynaptic EPSPs were sufficiently strong to evoke firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold and nociceptive high-threshold primary afferent inputs, and can function as wide-dynamic-range neurons able to directly connect deep dorsal horn with the major nociceptive projection area lamina I.

  3. Environmental impact assessment of radionuclide and metal contamination at the former U site at Kadji Sai, Kyrgyzstan.

    PubMed

    Lind, O C; Stegnar, P; Tolongutov, B; Rosseland, B O; Strømman, G; Uralbekov, B; Usubalieva, A; Solomatina, A; Gwynn, J P; Lespukh, E; Salbu, B

    2013-09-01

    During 1949-1967, a U mine, a coal-fired thermal power plant and a processing plant for the extraction of U from the produced ash were operated at the Kadji Sai U mining site in Tonsk district, Issyk-Kul County, Kyrgyzstan. The Kadji Sai U legacy site represents a source of contamination of the local environment by naturally occurring radionuclides and associated trace elements. To assess the environmental impact of radionuclides and trace metals at the site, field expeditions were performed in 2007 and 2008 by the Joint collaboration between Norway, Kazakhstan, Kyrgyzstan, Tajikistan (JNKKT) project and the NATO SfP RESCA project. In addition to in situ gamma and Rn dose rate measurements, sampling included at site fractionation of water and sampling of water, fish, sediment, soils and vegetation. The concentrations of radionuclides and trace metals in water from Issyk-Kul Lake were in general low, but surprisingly high for As. Uptake of U and As was also observed in fish from the lake with maximum bioconcentration factors for liver of 1.6 and 75, respectively. The concentrations of U in water within the Kadji Sai area varied from 0.01 to 0.05 mg/L, except for downstream from the mining area where U reached a factor of 10 higher, 0.2 mg/L. Uranium concentrations in the drinking water of Kadji Sai village were about the level recommended by the WHO for drinking water. The (234)U/(238)U activity ratio reflected equilibrium conditions in the mining pond, but far from equilibrium outside this area (reaching 2.3 for an artesian well). Uranium, As and Ni were mainly present as low molecular mass (LMM, less than 10 kDa) species in all samples, indicating that these elemental species are mobile and potentially bioavailable. The soils from the mining sites were enriched in U, As and trace metals. Hot spots with elevated radioactivity levels were easily detected in Kadji Sai and radioactive particles were observed. The presence of particles carrying significant amount of

  4. Rat isolated phrenic nerve-diaphragm preparation for pharmacological study of muscle spindle afferent activity: effect of oxotremorine.

    PubMed Central

    Ganguly, D K; Nath, D N; Ross, H G; Vedasiromoni, J R

    1978-01-01

    1. Muscle spindle afferent discharges exhibiting an approximately linear length-frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve-diaphragm preparation of the rat. 2. Muscle spindle afferent discharges could be identified by their characteristic "spindle pause" during muscle contraction and by their response to succinylcholine. 3. Cholinergic influence on spontaneous and stretch-induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)-Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles. 4. Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium-3 and (+)-tubocurarine failed to affect the rate of spontaneous and stretch-induced spindle discharges. 5. Oxotremorine markedly increased the rate of spontaneous and stretch-induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium-3 and (+)-tubocurarine. 6. These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents and hyperactive in Parkinsonian patients. PMID:151569

  5. Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.

    PubMed

    Phillis, Benjamin D; Martin, Chris M; Kang, Daiwu; Larsson, Håkan; Lindström, Erik A; Martinez, Vicente; Blackshaw, L Ashley

    2009-08-07

    The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.

  6. Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

    PubMed

    Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

    2017-01-01

    Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity ( P <0.05). The stress relaxed less in the diabetic intestinal segment ( P <0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

  7. On the nature of the afferent fibers of oculomotor nerve.

    PubMed

    Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

    1989-03-01

    The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

  8. Plasticity of gastrointestinal vagal afferent satiety signals.

    PubMed

    Page, A J; Kentish, S J

    2017-05-01

    The vagal link between the gastrointestinal tract and the central nervous system (CNS) has numerous vital functions for maintaining homeostasis. The regulation of energy balance is one which is attracting more and more attention due to the potential for exploiting peripheral hormonal targets as treatments for conditions such as obesity. While physiologically, this system is well tuned and demonstrated to be effective in the regulation of both local function and promoting/terminating food intake the neural connection represents a susceptible pathway for disruption in various disease states. Numerous studies have revealed that obesity in particularly is associated with an array of modifications in vagal afferent function from changes in expression of signaling molecules to altered activation mechanics. In general, these changes in vagal afferent function in obesity further promote food intake instead of the more desirable reduction in food intake. It is essential to gain a comprehensive understanding of the mechanisms responsible for these detrimental effects before we can establish more effective pharmacotherapies or lifestyle strategies for the treatment of obesity and the maintenance of weight loss. © 2016 John Wiley & Sons Ltd.

  9. Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways

    PubMed Central

    Kaji, Izumi; Akiba, Yasutada; Kato, Ikuo; Maruta, Koji; Kuwahara, Atsukazu

    2017-01-01

    Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose dependently increased the rate of duodenal HCO3− secretion in perfused duodenal loops of anesthetized rats. Xenin was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the xenin/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of xenin-8 or xenin-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1, substance P (SP) receptor (NK1), or 5-hydroxytryptamine (5-HT)3, but not NTS2, inhibited the responses to xenin. Xenin-evoked Cl- secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodium channel Nav1.8 in combination with TTX, suggesting that peripheral xenin augments duodenal HCO3− and Cl− secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released xenin may account for its secretory effects in the duodenum. PMID:28115552

  10. Role of afferent input in load-dependent plasticity of rat muscle

    NASA Astrophysics Data System (ADS)

    Kawano, F.; Umemoto, S.; Higo, Y.; Kawabe, N.; Wang, X. D.; Lan, Y. B.; Ohira, Y.

    We have been studying the role of afferent input in the plasticity of skeletal muscles. The present study was performed to investigate the mechanisms responsible for the deafferentation-related inhibition of the compensatory hypertrophy in rat soleus muscle. Adult male Wistar rats were randomly separated into the control, functionally overloaded (FO), and functionally overloaded + deafferentation (FO+DA) group. The tendons of plantaris and gastrocnemius muscles were transected in the FO rats. The dorsal roots of the spinal cord at the L4-5 segmental levels were additionally transected in the FO+DA rats. The sampling of the soleus was performed 2 weeks after the surgery and ambulation recovery. The single muscle fibers were isolated in low-calcium relaxing solution. Further, the myonuclei or argyrophilic nucleolar organizer regions (AgNORs) were stained. Significant increase of the fiber cross-sectional area (CSA) was seen in the FO, but not in the FO+DA, rats. The myonuclear number in fiber was significantly decreased by FO. Addition of DA to FO further promoted the reduction of myonuclear number. The mean nucleus size and DNA content in single nucleus in all groups were identical. Although a single or double AgNORs were seen in ~90% of myonuclei in the control rats, their distributions were 72 and 76% in the FO and FO+DA rats, respectively (p<0.05). More myonuclei containing 3-5 AgNORs were noted in the FO and FO+DA rats. The mean number of the AgNORs per myonucleus was 1.7 in the control, 2.1 in both FO and FO+DA rats (p<0.05). It was suggested that the FO-related increase of the number of AgNORs may be responsible for the induction of compensatory hypertrophy. It was also indicated that intact afferent input plays an essential role in these phenomena.

  11. The visceromotor and somatic afferent nerves of the penis.

    PubMed

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  12. Vagal Afferent Innervation of the Lower Esophageal Sphincter

    PubMed Central

    Powley, Terry L.; Baronowsky, Elizabeth A.; Gilbert, Jared M.; Hudson, Cherie N.; Martin, Felecia N.; Mason, Jacqueline K.; McAdams, Jennifer L.; Phillips, Robert J.

    2013-01-01

    To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions. PMID:23583280

  13. Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

    PubMed

    Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

    2012-04-01

    To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation.

  14. Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

    PubMed Central

    Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

    2017-01-01

    Background Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. PMID:29238211

  15. Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

    PubMed

    Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

    2016-01-01

    A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

  16. Afferent projections to the deep mesencephalic nucleus in the rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Veazey, R.B.; Severin, C.M.

    1982-01-10

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medialmore » and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist.« less

  17. Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

    PubMed Central

    Umeda, Tatsuya; Seki, Kazuhiko; Sato, Masa-aki; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

    2012-01-01

    Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. PMID:23112841

  18. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    PubMed Central

    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  19. Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues.

    PubMed

    Darques, J L; Jammes, Y

    1997-03-07

    Recordings of group IV afferent activity of tibialis anterior muscle were performed in paralysed rabbits during runs of electrically induced fatigue produced by direct muscle stimulation at a high (100 Hz, high-frequency fatigue HFF) or a low rate (10 Hz, low-frequency fatigue LFF). In addition to analysis of afferent nerve action potentials, muscle force and compound muscle action potentials (M waves) elicited by direct muscle stimulation with single shocks were recorded. Changes in M wave configuration were used as an index of the altered propagation of membrane potentials and the associated efflux of potassium from muscle fibers. The data show that increased group IV afferent activity occurred during LFF as well as HFF trials and developed parallel with force failure. Enhanced afferent activity was significantly higher during LFF (maximal delta f(impulses) = 249 +/- 35%) than HFF (147 +/- 45%). No correlation was obtained between the responses of group IV afferents to LFF or to pressure exerted on tibialis anterior muscle. On the other hand, decreased M wave amplitude was minimal with LFF while it was pronounced with HFF. Close correlations were found between fatigue-induced activation of group IV afferents and decreases in force or M wave amplitude, but their strength was significantly higher with LFF compared to HFF. Thus, electrically induced fatigue activates group IV muscle afferents with a prominent effect of low-frequency stimulation. The mechanism of muscle afferent stimulation does not seem to be due to the sole increase in extracellular potassium concentration, but also by the efflux of muscle metabolites, present during fatiguing contractions at low rate of stimulation.

  20. Ankle joint movements are encoded by both cutaneous and muscle afferents in humans.

    PubMed

    Aimonetti, Jean-Marc; Roll, Jean-Pierre; Hospod, Valérie; Ribot-Ciscar, Edith

    2012-08-01

    We analyzed the cutaneous encoding of two-dimensional movements by investigating the coding of movement velocity for differently oriented straight-line movements and the coding of complex trajectories describing cursive letters. The cutaneous feedback was then compared with that of the underlying muscle afferents previously recorded during the same "writing-like" movements. The unitary activity of 43 type II cutaneous afferents was recorded in the common peroneal nerve in healthy subjects during imposed ankle movements. These movements consisted first of ramp-and-hold movements imposed at two different and close velocities in seven directions and secondly of "writing-like" movements. In both cases, the responses were analyzed using the neuronal population vector model. The results show that movement velocity encoding depended on the direction of the ongoing movement. Discriminating between two velocities therefore involved processing the activity of afferent populations located in the various skin areas surrounding the moving joint, as shown by the statistically significant difference observed in the amplitude of the sum vectors. Secondly, "writing-like" movements induced cutaneous neuronal patterns of activity, which were reproducible and specific to each trajectory. Lastly, the "cutaneous neuronal trajectories," built by adding the sum vectors tip-to-tail, nearly matched both the movement trajectories and the "muscle neuronal trajectories," built from previously recorded muscle afferents. It was concluded that type II cutaneous and the underlying muscle afferents show similar encoding properties of two-dimensional movement parameters. This similarity is discussed in relation to a central gating process that would for instance increase the gain of cutaneous inputs when muscle information is altered by the fusimotor drive.

  1. Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

    PubMed

    Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

    2016-10-15

    In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Physiology of primary saccular afferents of goldfish: implications for Mauthner cell response.

    PubMed

    Fay, R R

    1995-01-01

    Mauthner cells receive neurally coded information from the otolith organs in fishes, and it is most likely that initiation and directional characteristics of the C-start response depend on this input. In the goldfish, saccular afferents are sensitive to sound pressure (< -30 dB re: 1 dyne cm-2) in the most sensitive frequency range (200 to 800 Hz). This input arises from volume fluctuations of the swimbladder in response to the sound pressure waveform and is thus nondirectional. Primary afferents of the saccule, lagena, and utricle of the goldfish also respond with great sensitivity to acoustic particle motion (< 1 nanometer between 100 and 200 Hz). This input arises from the acceleration of the fish in a sound field and is inherently directional. Saccular afferents can be divided into two groups based on their tuning: one group is tuned at about 250 Hz, and the other tuned between 400 Hz and 1 kHz. All otolithic primary afferents phaselock to sinusoids throughout the frequency range of hearing (up to about 2 kHz). Based on physiological and behavioral studies on Mauthner cells, it appears that highly correlated binaural input to the M-cell, from the sacculi responding to sound pressure, may be required for a decision to respond but that the direction of the response is extracted from small deviations from a perfect interaural correlation arising from the directional response of otolith organs to acoustic particle motion.

  3. Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.

    PubMed

    Shanks, Julia; Xia, Zhiqiu; Lisco, Steven J; Rozanski, George J; Schultz, Harold D; Zucker, Irving H; Wang, Han-Jun

    2018-06-01

    The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory

  4. Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.

    PubMed

    Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

    2011-10-24

    Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Spatiotemporal processing of linear acceleration: primary afferent and central vestibular neuron responses

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Dickman, J. D.

    2000-01-01

    Spatiotemporal convergence and two-dimensional (2-D) neural tuning have been proposed as a major neural mechanism in the signal processing of linear acceleration. To examine this hypothesis, we studied the firing properties of primary otolith afferents and central otolith neurons that respond exclusively to horizontal linear accelerations of the head (0.16-10 Hz) in alert rhesus monkeys. Unlike primary afferents, the majority of central otolith neurons exhibited 2-D spatial tuning to linear acceleration. As a result, central otolith dynamics vary as a function of movement direction. During movement along the maximum sensitivity direction, the dynamics of all central otolith neurons differed significantly from those observed for the primary afferent population. Specifically at low frequencies (afferents that peaked in phase with linear acceleration. At least three different groups of central response dynamics were described according to the properties observed for motion along the maximum sensitivity direction. "High-pass" neurons exhibited increasing gains and phase values as a function of frequency. "Flat" neurons were characterized by relatively flat gains and constant phase lags (approximately 20-55 degrees ). A few neurons ("low-pass") were characterized by decreasing gain and phase as a function of frequency. The response dynamics of central otolith neurons suggest that the approximately 90 degrees phase lags observed at low frequencies are not the result of a neural integration but rather the effect of nonminimum phase behavior, which could arise at least partly through spatiotemporal convergence. Neither afferent nor central otolith neurons discriminated between gravitational and inertial components of linear acceleration. Thus response sensitivity was indistinguishable during 0.5-Hz pitch oscillations and fore-aft movements

  6. Direct and Indirect Regulation of Spinal Cord Ia Afferent Terminal Formation by the γ-Protocadherins

    PubMed Central

    Prasad, Tuhina; Weiner, Joshua A.

    2011-01-01

    The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons (MNs), do not undergo excessive apoptosis in Pcdh-γdel/del null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants appear clumped, and fill the space between individual MNs; quantitative analysis shows a ~2.5-fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons (vINs), many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of vINs, which act as collateral Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for vINs; Hb9-Cre for MNs) also revealed a direct requirement for the γ-Pcdhs in Ia neurons and vINs, but not in MNs themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of vINs that act as collateral Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target vINs. PMID:22275881

  7. Direct and Indirect Regulation of Spinal Cord Ia Afferent Terminal Formation by the γ-Protocadherins.

    PubMed

    Prasad, Tuhina; Weiner, Joshua A

    2011-01-01

    The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons (MNs), do not undergo excessive apoptosis in Pcdh-γ(del/del) null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants appear clumped, and fill the space between individual MNs; quantitative analysis shows a ~2.5-fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons (vINs), many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of vINs, which act as collateral Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for vINs; Hb9-Cre for MNs) also revealed a direct requirement for the γ-Pcdhs in Ia neurons and vINs, but not in MNs themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of vINs that act as collateral Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target vINs.

  8. The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

    PubMed

    Nakamura, S I; Takahashi, K; Takahashi, Y; Yamagata, M; Moriya, H

    1996-07-01

    The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

  9. Immunomodulation of afferent neurons in guinea-pig isolated airway.

    PubMed

    Riccio, M M; Myers, A C; Undem, B J

    1996-03-01

    1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P < 0.005). Mechanical sensitivities of afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) from non-immunized control guinea-pig airways were unaffected by antigen (n = 13). 4. Antigen did not overtly cause action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in

  10. Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses

    PubMed Central

    Ikeda, Ryo; Cha, Myeounghoon; Ling, Jennifer; Jia, Zhanfeng; Coyle, Dennis; Gu, Jianguo G.

    2014-01-01

    SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions. PMID:24746027

  11. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    PubMed

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  12. Role of presynaptic inputs to proprioceptive afferents in tuning sensorimotor pathways of an insect joint control network.

    PubMed

    Sauer, A E; Büschges, A; Stein, W

    1997-04-01

    The femur-tibia (FT) joint of insects is governed by a neuronal network that controls activity in tibial motoneurons by processing sensory information about tibial position and movement provided by afferents of the femoral chordotonal organ (fCO). We show that central arborizations of fCO afferents receive presynaptic depolarizing synaptic inputs. With an average resting potential of -71.9 +/- 3.72 mV (n = 10), the reversal potential of these potentials is on average -62.8 +/- 2.3 mV (n = 5). These synaptic potentials occur either spontaneously or are related to movements at the fCO. They are thus induced by signals from other fCO afferents. Therefore, the synaptic inputs to fCO afferents are specific and depend on the sensitivity of the individual afferent affected. These potentials reduce the amplitude of concurrent afferent action potentials. Bath application of picrotoxin, a noncompetitive blocker of chloride ion channels, blocks these potentials, which indicates that they are mediated by chloride ions. From these results, it is concluded that these are inhibitory synaptic potentials generated in the central terminals of fCO afferents. Pharmacologic removal of these potentials affects the tuning of the complete FT control system. Following removal, the dependence of the FT control loop on the tibia position increases relative to the dependency on the velocity of tibia movements. This is due to changes in the relative weighting of the position and velocity signals in the parallel interneuronal pathways from the fCO onto tibial motoneurons. Consequently, the FT joint is no longer able to perform twig mimesis (i.e., catalepsy), which is known to rely on a low position compared to the high-velocity dependency of the FT control system.

  13. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    PubMed Central

    Groth, Michael; Helbig, Tanja; Grau, Veronika; Kummer, Wolfgang; Haberberger, Rainer V

    2006-01-01

    Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (35%) than pulmonary afferents (20%). TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive). Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli. PMID:16813657

  14. Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation

    PubMed Central

    Biddinger, Jessica E.; Baquet, Zachary C.; Jones, Kevin R.; McAdams, Jennifer

    2013-01-01

    A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout (SM-NT-3KO) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3KO mice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3KO mice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3KO mice compared with controls. The increases in meal duration and first meal size of SM-NT-3KO mice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation. PMID:24068045

  15. Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise.

    PubMed

    Hureau, Thomas J; Weavil, Joshua C; Thurston, Taylor S; Broxterman, Ryan M; Nelson, Ashley D; Bledsoe, Amber D; Jessop, Jacob E; Richardson, Russell S; Wray, D Walter; Amann, Markus

    2018-04-15

    We investigated the contribution of group III/IV muscle afferents to carotid baroreflex resetting during electrically evoked (no central command) and voluntary (requiring central command) isometric knee extension exercise. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive group III/IV leg muscle afferent feedback. Spontaneous carotid baroreflex control was assessed by loading and unloading the carotid baroreceptors with a variable pressure neck chamber. Group III/IV muscle afferents did not influence spontaneous carotid baroreflex responsiveness at rest or during exercise. Afferent feedback accounted for at least 50% of the exercise-induced increase in the carotid baroreflex blood pressure and heart rate operating points, adjustments that are critical for an appropriate cardiovascular response to exercise. These findings suggest that group III/IV muscle afferent feedback is, independent of central command, critical for the resetting of the carotid baroreflex blood pressure and heart rate operating points, but not for spontaneous baroreflex responsiveness. This study sought to comprehensively investigate the role of metabolically and mechanically sensitive group III/IV muscle afferents in carotid baroreflex responsiveness and resetting during both electrically evoked (EVO, no central command) and voluntary (VOL, requiring central command) isometric single-leg knee-extension (15% of maximal voluntary contraction; MVC) exercise. Participants (n = 8) were studied under control conditions (CTRL) and following lumbar intrathecal fentanyl injection (FENT) to inhibit μ-opioid receptor-sensitive lower limb muscle afferents. Spontaneous carotid baroreflex control of mean arterial pressure (MAP) and heart rate (HR) were assessed following rapid 5 s pulses of neck pressure (NP, +40 mmHg) or suction (NS, -60 mmHg). Resting MAP (87 ± 10 mmHg) and HR (70 ± 8 bpm) were similar between CTRL and FENT conditions (P

  16. Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

    PubMed

    Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

    2015-04-01

    Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

  17. Task- and time-dependent modulation of Ia presynaptic inhibition during fatiguing contractions performed by humans

    PubMed Central

    Maerz, Adam H.; Gould, Jeffrey R.; Enoka, Roger M.

    2011-01-01

    Presynaptic modulation of Ia afferents converging onto the motor neuron pool of the extensor carpi radialis (ECR) was compared during contractions (20% of maximal force) sustained to failure as subjects controlled either the angular position of the wrist while supporting an inertial load (position task) or exerted an equivalent force against a rigid restraint (force task). Test Hoffmann (H) reflexes were evoked in the ECR by stimulating the radial nerve above the elbow. Conditioned H reflexes were obtained by stimulating either the median nerve above the elbow or at the wrist (palmar branch) to assess presynaptic inhibition of homonymous (D1 inhibition) and heteronymous Ia afferents (heteronymous Ia facilitation), respectively. The position task was briefer than the force task (P = 0.001), although the maximal voluntary force and electromyograph for ECR declined similarly at failure for both tasks. Changes in the amplitude of the conditioned H reflex were positively correlated between the two conditioning methods (P = 0.02) and differed between the two tasks (P < 0.05). The amplitude of the conditioned H reflex during the position task first increased (129 ± 20.5% of the initial value, P < 0.001) before returning to its initial value (P = 0.22), whereas it increased progressively during the force task to reach 122 ± 17.4% of the initial value at failure (P < 0.001). Moreover, changes in conditioned H reflexes were associated with the time to task failure and force fluctuations. The results suggest a task- and time-dependent modulation of presynaptic inhibition of Ia afferents during fatiguing contractions. PMID:21543747

  18. Corollary discharge inhibition of wind-sensitive cercal giant interneurons in the singing field cricket

    PubMed Central

    Hedwig, Berthold

    2014-01-01

    Crickets carry wind-sensitive mechanoreceptors on their cerci, which, in response to the airflow produced by approaching predators, triggers escape reactions via ascending giant interneurons (GIs). Males also activate their cercal system by air currents generated due to the wing movements underlying sound production. Singing males still respond to external wind stimulation, but are not startled by the self-generated airflow. To investigate how the nervous system discriminates sensory responses to self-generated and external airflow, we intracellularly recorded wind-sensitive afferents and ventral GIs of the cercal escape pathway in fictively singing crickets, a situation lacking any self-stimulation. GI spiking was reduced whenever cercal wind stimulation coincided with singing motor activity. The axonal terminals of cercal afferents showed no indication of presynaptic inhibition during singing. In two ventral GIs, however, a corollary discharge inhibition occurred strictly in phase with the singing motor pattern. Paired intracellular recordings revealed that this inhibition was not mediated by the activity of the previously identified corollary discharge interneuron (CDI) that rhythmically inhibits the auditory pathway during singing. Cercal wind stimulation, however, reduced the spike activity of this CDI by postsynaptic inhibition. Our study reveals how precisely timed corollary discharge inhibition of ventral GIs can prevent self-generated airflow from triggering inadvertent escape responses in singing crickets. The results indicate that the responsiveness of the auditory and wind-sensitive pathway is modulated by distinct CDIs in singing crickets and that the corollary discharge inhibition in the auditory pathway can be attenuated by cercal wind stimulation. PMID:25318763

  19. The modulation of visceral functions by somatic afferent activity.

    PubMed

    Sato, A; Schmidt, R F

    1987-01-01

    We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

  20. Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells

    PubMed Central

    Ji, Young Rae; Warrier, Sunita; Jiang, Tao

    2018-01-01

    The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets. PMID:29671737

  1. Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

    PubMed Central

    Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

    1992-01-01

    1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

  2. Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy.

    PubMed

    Sadeghi, Soroush G; Minor, Lloyd B; Cullen, Kathleen E

    2007-02-01

    We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1-12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5-15 Hz (20-80 degrees /s) and fast whole-body rotations reaching velocities of 500 degrees /s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of < or =2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

  3. Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

    PubMed Central

    Byblow, Winston D.; Stinear, Cathy M.; Smith, Marie-Claire; Bjerre, Lotte; Flaskager, Brian K.; McCambridge, Alana B.

    2012-01-01

    Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality

  4. The renal nerves in chronic heart failure: efferent and afferent mechanisms

    PubMed Central

    Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

    2015-01-01

    The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

  5. Measurement of the relative afferent pupillary defect in retinal detachment.

    PubMed

    Bovino, J A; Burton, T C

    1980-07-01

    A swinging flashlight test and calibrated neutral density filters were used to quantitate the depth of relative afferent pupillary defects in ten patients with retinal detachment. Postoperatively, the pupillary responses returned to normal in seven of nine patients with anatomically successful surgery.

  6. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses

    PubMed Central

    Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T.; Wangsawihardja, Felix; Ricci, Anthony J.; Mustapha, Mirna

    2016-01-01

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. PMID:26386265

  7. [Myofibroblasts and afferent signalling in the urinary bladder. A concept].

    PubMed

    Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

    2008-09-01

    Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

  8. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

    PubMed Central

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2016-01-01

    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  9. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

    PubMed

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2016-01-01

    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  10. Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways.

    PubMed Central

    Ricco, M M; Kummer, W; Biglari, B; Myers, A C; Undem, B J

    1996-01-01

    1. The present study addressed the hypothesis that jugular and nodose vagal ganglia contain the somata of functionally and anatomically distinct airway afferent fibres. 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF). In the nodose ganglion, NF-immunoreactive neurones accounted for about 98% of the Fast Blue-labelled cells while in the jugular ganglion they accounted for approximately 48%. SP and NF immunoreactivity was never (n = 100) observed in the same cell suggesting that the antisera labelled distinct populations. 3. Electrophysiological investigations were performed using an in vitro guinea-pig tracheal and bronchial preparation with intact afferent vagal pathways, including nodose and jugular ganglia. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in either ganglion. 4. The nodose ganglion contained the somata of mainly fast-conducting tracheal A delta fibres whereas the jugular ganglion contained equal numbers of C fibre and A delta fibre tracheal afferent somata. The nodose A delta neurones adapted rapidly to mechanical stimulation, had relatively low mechanical thresholds, were not activated by capsaicin and adapted rapidly to a hyperosmotic stimulus. By contrast, jugular A delta and C fibres adapted slowly to mechanical stimulation, were often activated by capsaicin, had higher mechanical thresholds and displayed a slow adaptation to a hyperosmotic stimulus. 5. The anatomical, physiological and pharmacological data provide evidence to support the contention that the vagal ganglionic source of the fibre supplying the airways ultimately dictates its neurochemical and physiological phenotype. Images Figure 1 PMID:8910234

  11. Kv1 channels and neural processing in vestibular calyx afferents.

    PubMed

    Meredith, Frances L; Kirk, Matthew E; Rennie, Katherine J

    2015-01-01

    Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.

  12. Retrograde double-labeling demonstrates convergent afferent innervation of the prostate and bladder.

    PubMed

    Lee, Sanghee; Yang, Guang; Xiang, William; Bushman, Wade

    2016-06-01

    Prostatic inflammation is a common histologic finding in men with lower urinary tract symptoms (LUTS). It has been postulated that prostatic inflammation could sensitize afferent neurons innervating the bladder and thereby produce changes in voiding behavior. In support of this, we demonstrate an anatomic basis for pelvic cross-talk involving the prostate and bladder. Retrograde labeling was performed by an application of a neuro-tracer Fast Blue (FB) to one side of either the anterior prostate (AP), dorsal lateral prostate (DLP)/ventral prostate (VP), bladder, or seminal vesicle (SV). Examination of dorsal root ganglion (DRG) neuron labeling revealed shared afferent innervation of the prostate and bladder at spinal segments of T13, L1, L2, L6, and S1. Dual labeling was performed by an application of FB and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyaine perchlorate (DiI) to the AP and bladder, respectively. We observed double-labeled DRG neurons at T13, L1, L2, L6, and S1--a finding that proves convergent innervation of prostate and bladder. Our observations demonstrate the potential for neural cross-talk between the prostate and bladder and support a postulated mechanism that prostatic inflammation may induce hyper-sensitization of bladder afferents and produce irritative LUTS. © 2016 Wiley Periodicals, Inc.

  13. The organization of the lateral geniculate nucleus and of the geniculocortical pathway that develops without retinal afferents.

    PubMed

    Guillery, R W; Ombrellaro, M; LaMantia, A L

    1985-06-01

    The fine structure and cortical connections of the dorsal lateral geniculate nucleus have been studied in postnatal (3.5-14-month-old) ferrets in which all retinal afferents had been removed prenatally at the time these fibers are first starting to invade the nucleus. The synaptic profiles in the mature nucleus show the cytological characteristics and arrangements that would remain if the retinal afferents were removed, with no significant compensatory ingrowth of foreign specific afferents. The nucleus is reduced in overall volume, but the geniculocortical and corticogeniculate interconnections show an essentially normal topography. Although in these experiments the geniculocortical projections can establish a normal topographic pattern in the absence of retinal afferents an accompanying paper shows that this topographic pattern can also be modified in the presence of abnormal retinogeniculate inputs. We conclude that two separate mechanisms contribute to the formation of retinal maps within the geniculocortical pathways and that different interactions between these two mechanisms produce the different patterns of abnormal geniculocortical pathways that have been described in pigment-deficient cats, mink and ferrets.

  14. Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.

    PubMed

    Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A

    2014-11-01

    We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Optimal delineation of single C-tactile and C-nociceptive afferents in humans by latency slowing.

    PubMed

    Watkins, Roger H; Wessberg, Johan; Backlund Wasling, Helena; Dunham, James P; Olausson, Håkan; Johnson, Richard D; Ackerley, Rochelle

    2017-04-01

    C-mechanoreceptors in humans comprise a population of unmyelinated afferents exhibiting a wide range of mechanical sensitivities. C-mechanoreceptors are putatively divided into those signaling gentle touch (C-tactile afferents, CTs) and nociception (C-mechanosensitive nociceptors, CMs), giving rise to positive and negative affect, respectively. We sought to distinguish, compare, and contrast the properties of a population of human C-mechanoreceptors to see how fundamental the divisions between these putative subpopulations are. We used microneurography to record from individual afferents in humans and applied electrical and mechanical stimulation to their receptive fields. We show that C-mechanoreceptors can be distinguished unequivocally into two putative populations, comprising CTs and CMs, by electrically evoked spike latency changes (slowing). After both natural mechanical stimulation and repetitive electrical stimulation there was markedly less latency slowing in CTs compared with CMs. Electrical receptive field stimulation, which bypasses the receptor end organ, was most effective in classifying C-mechanoreceptors, as responses to mechanical receptive field stimulation overlapped somewhat, which may lead to misclassification. Furthermore, we report a subclass of low-threshold CM responding to gentle mechanical stimulation and a potential subclass of CT afferent displaying burst firing. We show that substantial differences exist in the mechanisms governing axonal conduction between CTs and CMs. We provide clear electrophysiological "signatures" (extent of latency slowing) that can be used in unequivocally identifying populations of C-mechanoreceptors in single-unit and multiunit microneurography studies and in translational animal research into affective touch. Additionally, these differential mechanisms may be pharmacologically targetable for separate modulation of positive and negative affective touch information. NEW & NOTEWORTHY Human skin encodes a

  16. Effects of stimulation of phrenic afferents on cervical respiratory interneurones and phrenic motoneurones in cats.

    PubMed Central

    Iscoe, S; Duffin, J

    1996-01-01

    1. In ten decerebrate, paralysed and ventilated cats, we tested the hypothesis that cervical (C5) respiratory interneurones mediate inhibition of phrenic motoneurone activity resulting from single shocks to the phrenic nerve. 2. Stimulus intensities sufficient to activate all afferents elicited (latency, 4.0 +/- 0.9 ms, mean +/- S.D.) a graded suppression of ipsilateral, but not contralateral (five of seven cats) phrenic nerve activity lasting, in six of seven cats, more than 70 ms and interrupted by a brief (approximately 6-18 ms duration) excitation at latencies between 7 and 30 ms. 3. In twenty-five ipsilateral motoneurones, peristimulus time average of the membrane potentials (-61 +/- 10 mV) showed no effect in eleven; of the fourteen that responded, ten had initial EPSPs (latency, 17.6 +/- 3.0 ms) and four initial IPSPs (latencies, 2.25-4.3 ms). Only one motoneurone had both. No responses with latencies > 60 ms were observed. 4. Peristimulus time averages of extracellular activity of thirty ipsilateral interneurones, twenty-five firing in inspiration (I) and five in expiration (E), showed diverse responses. The initial response of I interneurones was an excitation in eleven, a suppression of activity in nine, and no response in five. Latencies of excitations ranged from 2 to 36.5 ms (median, 14 ms) with durations ranging from 2 to 7 ms (mean, 4.4 +/- 1.6 ms). Latencies of suppression of activity ranged from 2 to 29 ms (median, 10 ms). Two E interneurones were excited (latencies, 11 and 15 ms; durations, 3.5 and 2 ms), two inhibited (latencies, 2 and 12 ms; durations, > 40 and 17 ms, respectively), and one did not respond. 5. In nine interneurones (seven I, two E), peristimulus time averages of the membrane potentials (mean, -62 +/- 14 mV) revealed no effect on three (all I). Of the six that responded, four (three I) had initial IPSPs, two (one I, one E) initial EPSPs. EPSPs had latencies of 11.5 (I interneurone) and 22 ms (E interneurone); the latencies of the

  17. ACTIVATION OF TRPA1 ON DURAL AFFERENTS: A POTENTIAL MECHANISM OF HEADACHE PAIN

    PubMed Central

    Edelmayer, Rebecca M.; Le, Larry N.; Yan, Jin; Wei, Xiaomei; Nassini, Romina; Materazzi, Serena; Preti, Delia; Appendino, Giovanni; Geppetti, Pierangelo; Dodick, David W.; Vanderah, Todd W.; Porreca, Frank; Dussor, Gregory

    2012-01-01

    Activation of transient receptor potential ankyrin-1 (TRPA1) on meningeal nerve endings has been suggested to contribute to environmental irritant-induced headache but this channel may also contribute to other forms of headache such as migraine. The preclinical studies described here examined functional expression of TRPA1 on dural afferents and investigated whether activation of TRPA1 contributes to headache-like behaviors. Whole-cell patch-clamp recordings were performed in vitro using two TRPA1 agonists, mustard oil (MO) and the environmental irritant umbellulone (UMB), on dural-projecting trigeminal ganglion neurons. Application of MO and UMB to dural afferents produced TRPA1-like currents in approximately 42% and 38% of cells, respectively. Using an established in vivo behavioral model of migraine-related allodynia, dural application of MO and UMB produced robust time-related tactile facial and hindpaw allodynia that was attenuated by pretreatment with the TRPA1 antagonist HC-030031. Additionally, MO or UMB were applied to the dura and exploratory activity was monitored for 30 minutes using an automated open-field activity chamber. Dural MO and UMB decreased the number of vertical rearing episodes and the time spent rearing in comparison to vehicle treated animals. This change in activity was prevented in rats pretreated with HC-030031 as well as sumatriptan, a clinically effective anti-migraine agent. These data indicate that TRPA1 is expressed on a substantial fraction of dural afferents and activation of meningeal TRPA1 produces behaviors consistent with those seen in patients during migraine attacks. Further, they suggest that activation of meningeal TRPA1 via endogenous or exogenous mechanisms can lead to afferent signaling and headache. PMID:22809691

  18. Hyperexcitability of bladder afferent neurons associated with reduction of Kv1.4 α-subunit in rats with spinal cord injury.

    PubMed

    Takahashi, Ryosuke; Yoshizawa, Tsuyoshi; Yunoki, Takakazu; Tyagi, Pradeep; Naito, Seiji; de Groat, William C; Yoshimura, Naoki

    2013-12-01

    To clarify the functional and molecular mechanisms inducing hyperexcitability of C-fiber bladder afferent pathways after spinal cord injury we examined changes in the electrophysiological properties of bladder afferent neurons, focusing especially on voltage-gated K channels. Freshly dissociated L6-S1 dorsal root ganglion neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley® rats. Whole cell patch clamp recordings were performed on individual bladder afferent neurons. Kv1.2 and Kv1.4 α-subunit expression levels were also evaluated by immunohistochemical and real-time polymerase chain reaction methods. Capsaicin sensitive bladder afferent neurons from spinal transected rats showed increased cell excitability, as evidenced by lower spike activation thresholds and a tonic firing pattern. The peak density of transient A-type K+ currents in capsaicin sensitive bladder afferent neurons from spinal transected rats was significantly less than that from spinal intact rats. Also, the KA current inactivation curve was displaced to more hyperpolarized levels after spinal transection. The protein and mRNA expression of Kv1.4 α-subunits, which can form transient A-type K+ channels, was decreased in bladder afferent neurons after spinal transection. Results indicate that the excitability of capsaicin sensitive C-fiber bladder afferent neurons is increased in association with reductions in transient A-type K+ current density and Kv1.4 α-subunit expression in injured rats. Thus, the Kv1.4 α-subunit could be a molecular target for treating overactive bladder due to neurogenic detrusor overactivity. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder.

    PubMed

    Downie, J W; Armour, J A

    1992-11-01

    The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure.

  20. Role of irregular otolith afferents in the steady-state nystagmus during off-vertical axis rotation

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Perachio, A. A.; Mustari, M. J.; Strunk, C. L.

    1992-01-01

    1. During constant velocity off-vertical axis rotations (OVAR) in the dark a compensatory ocular nystagmus is present throughout rotation despite the lack of a maintained signal from the semicircular canals. Lesion experiments and canal plugging have attributed the steady-state ocular nystagmus during OVAR to inputs from the otolith organs and have demonstrated that it depends on an intact velocity storage mechanism. 2. To test whether irregularly discharging otolith afferents play a crucial role in the generation of the steady-state eye nystagmus during OVAR, we have used anodal (inhibitory) currents bilaterally to selectively and reversibly block irregular vestibular afferent discharge. During delivery of DC anodal currents (100 microA) bilaterally to both ears, the slow phase eye velocity of the steady-state nystagmus during OVAR was reduced or completely abolished. The disruption of the steady-state nystagmus was transient and lasted only during the period of galvanic stimulation. 3. To distinguish a possible effect of ablation of the background discharge rates of irregular vestibular afferents on the velocity storage mechanism from specific contributions of the dynamic responses from irregular otolith afferents to the circuit responsible for the generation of the steady-state nystagmus, bilateral DC anodal galvanic stimulation was applied during optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN). No change in OKN and OKAN was observed.(ABSTRACT TRUNCATED AT 250 WORDS).

  1. Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

    PubMed Central

    Dideriksen, Jakob L.; Laine, Christopher M.; Dosen, Strahinja; Muceli, Silvia; Rocon, Eduardo; Pons, José L.; Benito-Leon, Julian; Farina, Dario

    2017-01-01

    Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient. PMID:28420958

  2. Anatomy and physiology of the afferent visual system.

    PubMed

    Prasad, Sashank; Galetta, Steven L

    2011-01-01

    The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Modulated discharge of Purkinje and stellate cells persists after unilateral loss of vestibular primary afferent mossy fibers in mice

    PubMed Central

    Yakhnitsa, V.

    2013-01-01

    Cerebellar Purkinje cells are excited by two afferent pathways: climbing and mossy fibers. Climbing fibers evoke large “complex spikes” (CSs) that discharge at low frequencies. Mossy fibers synapse on granule cells whose parallel fibers excite Purkinje cells and may contribute to the genesis of “simple spikes” (SSs). Both afferent systems convey vestibular information to folia 9c–10. After making a unilateral labyrinthectomy (UL) in mice, we tested how the discharge of CSs and SSs was changed by the loss of primary vestibular afferent mossy fibers during sinusoidal roll tilt. We recorded from cells identified by juxtacellular neurobiotin labeling. The UL preferentially reduced vestibular modulation of CSs and SSs in folia 8–10 contralateral to the UL. The effects of a UL on Purkinje cell discharge were similar in folia 9c–10, to which vestibular primary afferents project, and in folia 8–9a, to which they do not project, suggesting that vestibular primary afferent mossy fibers were not responsible for the UL-induced alteration of SS discharge. UL also induced reduced vestibular modulation of stellate cell discharge contralateral to the UL. We attribute the decreased modulation to reduced vestibular modulation of climbing fibers. In summary, climbing fibers modulate CSs directly and SSs indirectly through activation of stellate cells. Whereas vestibular primary afferent mossy fibers cannot account for the modulated discharge of SSs or stellate cells, the nonspecific excitation of Purkinje cells by parallel fibers may set an operating point about which the discharges of SSs are sculpted by climbing fibers. PMID:23966673

  4. The optimal neural strategy for a stable motor task requires a compromise between level of muscle cocontraction and synaptic gain of afferent feedback

    PubMed Central

    Dideriksen, Jakob L.; Negro, Francesco

    2015-01-01

    Increasing joint stiffness by cocontraction of antagonist muscles and compensatory reflexes are neural strategies to minimize the impact of unexpected perturbations on movement. Combining these strategies, however, may compromise steadiness, as elements of the afferent input to motor pools innervating antagonist muscles are inherently negatively correlated. Consequently, a high afferent gain and active contractions of both muscles may imply negatively correlated neural drives to the muscles and thus an unstable limb position. This hypothesis was systematically explored with a novel computational model of the peripheral nervous system and the mechanics of one limb. Two populations of motor neurons received synaptic input from descending drive, spinal interneurons, and afferent feedback. Muscle force, simulated based on motor unit activity, determined limb movement that gave rise to afferent feedback from muscle spindles and Golgi tendon organs. The results indicated that optimal steadiness was achieved with low synaptic gain of the afferent feedback. High afferent gains during cocontraction implied increased levels of common drive in the motor neuron outputs, which were negatively correlated across the two populations, constraining instability of the limb. Increasing the force acting on the joint and the afferent gain both effectively minimized the impact of an external perturbation, and suboptimal adjustment of the afferent gain could be compensated by muscle cocontraction. These observations show that selection of the strategy for a given contraction implies a compromise between steadiness and effectiveness of compensations to perturbations. This indicates that a task-dependent selection of neural strategy for steadiness is necessary when acting in different environments. PMID:26203102

  5. Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.

    PubMed

    Iwasaki, Yusaku; Maejima, Yuko; Suyama, Shigetomo; Yoshida, Masashi; Arai, Takeshi; Katsurada, Kenichi; Kumari, Parmila; Nakabayashi, Hajime; Kakei, Masafumi; Yada, Toshihiko

    2015-03-01

    Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity. Copyright © 2015 the American Physiological Society.

  6. Central anatomy of individual rapidly adapting low-threshold mechanoreceptors innervating the "hairy" skin of newborn mice: early maturation of hair follicle afferents.

    PubMed

    Woodbury, C J; Ritter, A M; Koerber, H R

    2001-07-30

    Adult skin sensory neurons exhibit characteristic projection patterns in the dorsal horn of the spinal gray matter that are tightly correlated with modality. However, little is known about how these patterns come about during the ontogeny of the distinct subclasses of skin sensory neurons. To this end, we have developed an intact ex vivo somatosensory system preparation in neonatal mice, allowing single, physiologically identified cutaneous afferents to be iontophoretically injected with Neurobiotin for subsequent histological analyses. The present report, centered on rapidly adapting mechanoreceptors, represents the first study of the central projections of identified skin sensory neurons in neonatal animals. Cutaneous afferents exhibiting rapidly adapting responses to sustained natural stimuli were encountered as early as recordings were made. Well-stained representatives of coarse (tylotrich and guard) and fine-diameter (down) hair follicle afferents, along with a putative Pacinian corpuscle afferent, were recovered from 2-7-day-old neonates. All were characterized by narrow, uninflected somal action potentials and generally low mechanical thresholds, and many could be activated via deflection of recently erupted hairs. The central collaterals of hair follicle afferents formed recurrent, flame-shaped arbors that were essentially miniaturized replicas of their adult counterparts, with identical laminar terminations. The terminal arbors of down hair afferents, previously undescribed in rodents, were distinct and consistently occupied a more superficial position than tylotrich and guard hair afferents. Nevertheless, the former extended no higher than the middle of the incipient substantia gelatinosa, leaving a clear gap more dorsally. In all major respects, therefore, hair follicle afferents display the same laminar specificity in neonates as they do in adults. The widely held misperception that their collaterals extend exuberant projections into pain

  7. Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

    PubMed Central

    Nishi, K.; Sakanashi, M.; Takenaka, F.

    1974-01-01

    1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

  8. Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone

    PubMed Central

    Holmes, Gregory M; Browning, Kirsteen N; Babic, Tanja; Fortna, Samuel R; Coleman, F Holly; Travagli, R Alberto

    2013-01-01

    Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and reduced by l-NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic-mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric-projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT-induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit. PMID:23587885

  9. Sensory Afferents Use Different Coding Strategies for Heat and Cold.

    PubMed

    Wang, Feng; Bélanger, Erik; Côté, Sylvain L; Desrosiers, Patrick; Prescott, Steven A; Côté, Daniel C; De Koninck, Yves

    2018-05-15

    Primary afferents transduce environmental stimuli into electrical activity that is transmitted centrally to be decoded into corresponding sensations. However, it remains unknown how afferent populations encode different somatosensory inputs. To address this, we performed two-photon Ca 2+ imaging from thousands of dorsal root ganglion (DRG) neurons in anesthetized mice while applying mechanical and thermal stimuli to hind paws. We found that approximately half of all neurons are polymodal and that heat and cold are encoded very differently. As temperature increases, more heating-sensitive neurons are activated, and most individual neurons respond more strongly, consistent with graded coding at population and single-neuron levels, respectively. In contrast, most cooling-sensitive neurons respond in an ungraded fashion, inconsistent with graded coding and suggesting combinatorial coding, based on which neurons are co-activated. Although individual neurons may respond to multiple stimuli, our results show that different stimuli activate distinct combinations of diversely tuned neurons, enabling rich population-level coding. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Axonal conduction block as a novel mechanism of prepulse inhibition

    PubMed Central

    Lee, A. H.; Megalou, E. V.; Wang, J.; Frost, W.N.

    2012-01-01

    In prepulse inhibition (PPI), the startle response to a strong, unexpected stimulus is diminished if shortly preceded by the onset of a different stimulus. Because deficits in this inhibitory gating process are a hallmark feature of schizophrenia and certain other psychiatric disorders, the mechanisms underlying PPI are of significant interest. We previously used the invertebrate model system Tritonia diomedea to identify the first cellular mechanism for PPI–presynaptic inhibition of transmitter release from the afferent neurons (S-cells) mediating the startle response. Here we report the involvement of a second, more powerful PPI mechanism in Tritonia: prepulse-elicited conduction block of action potentials traveling in the startle pathway caused by identified inhibitory interneurons activated by the prepulse. This example of axo-axonic conduction block–neurons in one pathway inhibiting the propagation of action potentials in another–represents a novel and potent mechanism of sensory gating in prepulse inhibition. PMID:23115164

  11. Decoding tactile afferent activity to obtain an estimate of instantaneous force and torque applied to the fingerpad

    PubMed Central

    Birznieks, Ingvars; Redmond, Stephen J.

    2015-01-01

    Dexterous manipulation is not possible without sensory information about object properties and manipulative forces. Fundamental neuroscience has been unable to demonstrate how information about multiple stimulus parameters may be continuously extracted, concurrently, from a population of tactile afferents. This is the first study to demonstrate this, using spike trains recorded from tactile afferents innervating the monkey fingerpad. A multiple-regression model, requiring no a priori knowledge of stimulus-onset times or stimulus combination, was developed to obtain continuous estimates of instantaneous force and torque. The stimuli consisted of a normal-force ramp (to a plateau of 1.8, 2.2, or 2.5 N), on top of which −3.5, −2.0, 0, +2.0, or +3.5 mNm torque was applied about the normal to the skin surface. The model inputs were sliding windows of binned spike counts recorded from each afferent. Models were trained and tested by 15-fold cross-validation to estimate instantaneous normal force and torque over the entire stimulation period. With the use of the spike trains from 58 slow-adapting type I and 25 fast-adapting type I afferents, the instantaneous normal force and torque could be estimated with small error. This study demonstrated that instantaneous force and torque parameters could be reliably extracted from a small number of tactile afferent responses in a real-time fashion with stimulus combinations that the model had not been exposed to during training. Analysis of the model weights may reveal how interactions between stimulus parameters could be disentangled for complex population responses and could be used to test neurophysiologically relevant hypotheses about encoding mechanisms. PMID:25948866

  12. Primary afferent neurons express functional delta opioid receptors in inflamed skin.

    PubMed

    Brederson, Jill-Desiree; Honda, Christopher N

    2015-07-21

    Peripherally-restricted opiate compounds attenuate hyperalgesia in experimental models of inflammatory pain, but have little discernable effect on nociceptive behavior in normal animals. This suggests that activation of opioid receptors on peripheral sensory axons contributes to decreased afferent activity after injury. Previously, we reported that direct application of morphine to cutaneous receptive fields decreased mechanical and heat-evoked responses in a population of C-fiber nociceptors in inflamed skin. Consistent with reported behavioral studies, direct application of morphine had no effect on fiber activity in control skin. The aim of the present study was to determine whether mechanical responsiveness of nociceptors innervating inflamed skin was attenuated by direct activation of delta opioid receptors (DORs) on peripheral terminals. An ex vivo preparation of rat plantar skin and tibial nerve was used to examine effects of a selective DOR agonist, deltorphin II, on responsiveness of single fibers innervating inflamed skin. Electrical recordings were made eighteen hours after injection of complete Freund's adjuvant into the hindpaw. Deltorphin II produced an inhibition of the mechanical responsiveness of single fibers innervating inflamed skin; an effect blocked by the DOR-selective antagonist, naltrindole. The population of units responsive to deltorphin II was identified as consisting of C fiber mechanical nociceptors. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle

    PubMed Central

    Contini, Donatella; Price, Steven D.

    2016-01-01

    Key points In the synaptic cleft between type I hair cells and calyceal afferents, K+ ions accumulate as a function of activity, dynamically altering the driving force and permeation through ion channels facing the synaptic cleft.High‐fidelity synaptic transmission is possible due to large conductances that minimize hair cell and afferent time constants in the presence of significant membrane capacitance.Elevated potassium maintains hair cells near a potential where transduction currents are sufficient to depolarize them to voltages necessary for calcium influx and synaptic vesicle fusion.Elevated potassium depolarizes the postsynaptic afferent by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels, and contributes to depolarizing the afferent to potentials where a single EPSP (quantum) can generate an action potential.With increased stimulation, hair cell depolarization increases the frequency of quanta released, elevates [K+]cleft and depolarizes the afferent to potentials at which smaller and smaller EPSPs would be sufficient to trigger APs. Abstract Fast neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. Here, we used dual patch‐clamp recordings from turtle vestibular hair cells and their afferent neurons to show that potassium ions accumulating in the synaptic cleft modulated membrane potentials and extended the range of information transfer. High‐fidelity synaptic transmission was possible due to large conductances that minimized hair cell and afferent time constants in the presence of significant membrane capacitance. Increased potassium concentration in the cleft maintained the hair cell near potentials that promoted the influx of calcium necessary for synaptic vesicle fusion. The elevated potassium concentration also depolarized the postsynaptic

  14. Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?

    PubMed Central

    Kaczmarek, D.; Ristikankare, J.

    2017-01-01

    Key points Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones.Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA).Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them.The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel. Abstract Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans‐spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post‐activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans‐spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent

  15. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    NASA Technical Reports Server (NTRS)

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

    1998-01-01

    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  16. Persistent pain after spinal cord injury is maintained by primary afferent activity.

    PubMed

    Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

    2014-08-06

    Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

  17. Stochastic resonance in the synaptic transmission between hair cells and vestibular primary afferents in development.

    PubMed

    Flores, A; Manilla, S; Huidobro, N; De la Torre-Valdovinos, B; Kristeva, R; Mendez-Balbuena, I; Galindo, F; Treviño, M; Manjarrez, E

    2016-05-13

    The stochastic resonance (SR) is a phenomenon of nonlinear systems in which the addition of an intermediate level of noise improves the response of such system. Although SR has been studied in isolated hair cells and in the bullfrog sacculus, the occurrence of this phenomenon in the vestibular system in development is unknown. The purpose of the present study was to explore for the existence of SR via natural mechanical-stimulation in the hair cell-vestibular primary afferent transmission. In vitro experiments were performed on the posterior semicircular canal of the chicken inner ear during development. Our experiments showed that the signal-to-noise ratio of the afferent multiunit activity from E15 to P5 stages of development exhibited the SR phenomenon, which was characterized by an inverted U-like response as a function of the input noise level. The inverted U-like graphs of SR acquired their higher amplitude after the post-hatching stage of development. Blockage of the synaptic transmission with selective antagonists of the NMDA and AMPA/Kainate receptors abolished the SR of the afferent multiunit activity. Furthermore, computer simulations on a model of the hair cell - primary afferent synapse qualitatively reproduced this SR behavior and provided a possible explanation of how and where the SR could occur. These results demonstrate that a particular level of mechanical noise on the semicircular canals can improve the performance of the vestibular system in their peripheral sensory processing even during embryonic stages of development. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Cross-correlation between vagal afferent impulses from pulmonary mechanoreceptors and high-frequency inflation (HFI) and deflation (HFD) in rabbits.

    PubMed

    Homma, I; Isobe, A; Iwase, M; Onimaru, H; Sibuya, M

    1987-04-10

    The effects of high-frequency airway inflation (HFI) and high-frequency airway deflation (HFD) generated by a triangular pressure pulse generator on pulmonary mechanoreceptors were examined. The cross-correlograms between vagal afferent impulses from the slowly adapting (SAR) and the rapidly adapting receptors (RAR) and the HFI or the HFD pulses were analysed. HFI stimulated SAR and RAR and HFD stimulated RAR, but inhibited SAR. The time lag of the mode in the correlogram between SAR and HFI was shorter than that of the mode in the correlogram between RAR and HFI. The span of the mode and the trough of SAR was shorter than the span of the mode of RAR. This may indicate that the time to peak of the generator potential of RAR is longer than that of SAR.

  19. What Is the Contribution of Ia-Afference for Regulating Motor Output Variability during Standing?

    PubMed

    König, Niklas; Ferraro, Matteo G; Baur, Heiner; Taylor, William R; Singh, Navrag B

    2017-01-01

    Motor variability is an inherent feature of all human movements, and describes the system's stability and rigidity during the performance of functional motor tasks such as balancing. In order to ensure successful task execution, the nervous system is thought to be able to flexibly select the appropriate level of variability. However, it remains unknown which neurophysiological pathways are utilized for the control of motor output variability. In responding to natural variability (in this example sway), it is plausible that the neuro-physiological response to muscular elongation contributes to restoring a balanced upright posture. In this study, the postural sway of 18 healthy subjects was observed while their visual and mechano-sensory system was perturbed. Simultaneously, the contribution of Ia-afferent information for controlling the motor task was assessed by means of H-reflex. There was no association between postural sway and Ia-afference in the eyes open condition, however up to 4% of the effects of eye closure on the magnitude of sway can be compensated by increased reliance on Ia-afference. Increasing the biomechanical demands by adding up to 40% bodyweight around the trunk induced a specific sway response, such that the magnitude of sway remained unchanged but its dynamic structure became more regular and stable (by up to 18%). Such regular sway patterns have been associated with enhanced cognitive involvement in controlling motor tasks. It therefore appears that the nervous system applies different control strategies in response to the perturbations: The loss of visual information is compensated by increased reliance on other receptors; while the specific regular sway pattern associated with additional weight-bearing was independent of Ia-afferent information, suggesting the fundamental involvement of supraspinal centers for the control of motor output variability.

  20. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

    PubMed Central

    Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

    2012-01-01

    Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

  1. Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells

    PubMed Central

    Siembab, Valerie C.; Gomez-Perez, Laura; Rotterman, Travis M.; Shneider, Neil A.; Alvarez, Francisco J.

    2015-01-01

    Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, like Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (Er81(−/−) knockout), weakened (Egr3(−/−) knockout) or strengthened (mlcNT3(+/−) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their de-selection and reduces motor axon synaptic density and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. PMID:26660356

  2. Tempol Protects Against Acute Renal Injury by Regulating PI3K/Akt/mTOR and GSK3β Signaling Cascades and Afferent Arteriolar Activity.

    PubMed

    Zhang, Gensheng; Wang, Qin; Wang, Wenwen; Yu, Minghua; Zhang, Suping; Xu, Nan; Zhou, Suhan; Cao, Xiaoyun; Fu, Xiaodong; Ma, Zufu; Liu, Ruisheng; Mao, Jianhua; Lai, En Yin

    2018-05-30

    Free radical scavenger tempol is a protective antioxidant against ischemic injury. Tubular epithelial apoptosis is one of the main changes in the renal ischemia/reperfusion (I/R) injury. Meanwhile some proteins related with apoptosis and inflammation are also involved in renal I/R injury. We tested the hypothesis that tempol protects against renal I/R injury by activating protein kinase B/mammalian target of rapamycin (PKB, Akt/mTOR) and glycogen synthase kinase 3β (GSK3β) pathways as well as the coordinating apoptosis and inflammation related proteins. The right renal pedicle of C57Bl/6 mouse was clamped for 30 minutes and the left kidney was removed in the study. The renal injury was assessed with serum parameters by an automatic chemistry analyzer. Renal expressions of Akt/mTOR and GSK3β pathways were measured by western blot in I/R mice treated with saline or tempol (50mg/kg) and compared with sham-operated mice. The levels of blood urea nitrogen (BUN), creatinine and superoxide anion (O2.-) increased, and superoxide dismutase (SOD) and catalase (CAT) decreased significantly after renal I/R injury. However, tempol treatment prevented the changes. Besides, I/R injury reduced renal expression of p-Akt, p-GSK3β, p-mTOR, Bcl2 and increased NF-κB, p-JNK and p53 in kidney, tempol significantly normalized these changes. In addition, renal I/R injury reduced the response of afferent arteriole to Angiotensin II (Ang II), while tempol treatment improved the activity of afferent arteriole. Tempol attenuates renal I/R injury. The protective mechanisms seem to relate with activation of PI3K/Akt/mTOR and GSK3β pathways, inhibition of cellular damage markers and inflammation factors, as well as improvement of afferent arteriolar activity. © 2018 The Author(s). Published by S. Karger AG, Basel.

  3. Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity.

    PubMed

    Campaniello, M A; Harrington, A M; Martin, C M; Ashley Blackshaw, L; Brierley, S M; Hughes, P A

    2016-01-01

    Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown. Myeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and NaV 1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice. MPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p < 0.05), and the abundance of IL-2R and NaV 1.7 mRNA was increased 3.5- and 2-fold (p < 0.001 for both) in colo-rectal DRG neurons. IL-2, an immune mediator from the adaptive arm of the immune response, affects colo-rectal afferent function, indicating these effects are not restricted to innate immune mediators. Colo-rectal afferent sensitivity to IL-2 is increased long after healing from inflammation. © 2015 John Wiley & Sons Ltd.

  4. Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

    PubMed Central

    Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

    1988-01-01

    1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

  5. Primary afferent activity, putative excitatory transmitters and extracellular potassium levels in frog spinal cord.

    PubMed

    Davidoff, R A; Hackman, J C; Holohean, A M; Vega, J L; Zhang, D X

    1988-03-01

    1. Changes in extracellular K+ activity were measured with ion-selective microelectrodes in the grey matter of the isolated hemisected frog spinal cord. The magnitude of the elevation of [K+]o (delta[K+]o) produced by repetitive stimulation (25 Hz, 10 s) of afferent fibres in the sciatic nerve was monotonically related to the strength of the electrical stimuli applied to the sciatic nerve. Repetitive stimulation of the largest diameter A alpha and A beta fibres, which were found histologically to comprise only 11% of the afferent axons in the dorsal root, elevated [K+]o to approximately 60% of the maximum level seen when all afferent fibres were stimulated. 2. Addition of Mg2+ (20 mM) to Ringer solution devoid of Mg2+ reduced delta[K+]o by over 85% suggesting that about 15% of delta[K+]o results from action potentials in presynaptic primary afferents. When 20 mM-Mg2+ was added to spinal cords bathed in Ringer solution containing a physiological (i.e. 1.0 mM) concentration of Mg2+, delta[K+]o was reduced by ca. 65-75% indicating that in spinal cords bathed in medium containing 'physiological' concentrations of Mg2+ about 25-35% of the K+ is released from primary afferent fibres. 3. Application of excitatory amino acids and agonists increased [K+]o with the following potency pattern: quisqualate greater than kainate greater than NMDA (N-methyl-D-aspartate) greater than glutamate greater than aspartate. 4. D(-)-2-Amino-5-phosphonovalerate (APV), an NMDA antagonist, reduced [K+]o by only about 50%, but kynurenate, an NMDA and non-NMDA antagonist, reduced [K+]o by approximately 85%; i.e. the same levels observed when synaptic transmission was blocked with 20 mM-Mg2+. These findings support the idea that synaptic release of excitatory amino acids such as L-glutamate and/or L-aspartate and subsequent activation of specific receptors by these putative transmitters are necessary for the postsynaptic component of delta[K+]o. 5. Addition of tachykinins elevated [K+]o but the

  6. Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

    PubMed Central

    Gladden, M H; Matsuzaki, H

    2002-01-01

    Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

  7. Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse.

    PubMed

    Cádiz-Moretti, Bernardita; Otero-García, Marcos; Martínez-García, Fernando; Lanuza, Enrique

    2016-03-01

    The medial amygdaloid nucleus (Me) is a key node in the socio-sexual brain, composed of anterior (MeA), posteroventral (MePV) and posterodorsal (MePD) subdivisions. These subdivisions have been suggested to play a different role in reproductive and defensive behaviours. In the present work we analyse the afferents of the three Me subdivisions using restricted injections of fluorogold in female outbred CD1 mice. The results reveal that the MeA, MePV and MePD share a common pattern of afferents, with some differences in the density of retrograde labelling in several nuclei. Common afferents to Me subdivisions include: the accessory olfactory bulbs, piriform cortex and endopiriform nucleus, chemosensory amygdala (receiving direct inputs from the olfactory bulbs), posterior part of the medial bed nucleus of the stria terminalis (BSTM), CA1 in the ventral hippocampus and posterior intralaminar thalamus. Minor projections originate from the basolateral amygdala and amygdalo-hippocampal area, septum, ventral striatum, several allocortical and periallocortical areas, claustrum, several hypothalamic structures, raphe and parabrachial complex. MeA and MePV share minor inputs from the frontal cortex (medial orbital, prelimbic, infralimbic and dorsal peduncular cortices), but differ in the lack of main olfactory projections to the MePV. By contrast, the MePD receives preferential projections from the rostral accessory olfactory bulb, the posteromedial BSTM and the ventral premammillary nucleus. In summary, the common pattern of afferents to the Me subdivisions and their interconnections suggest that they play cooperative instead of differential roles in the various behaviours (e.g., sociosexual, defensive) in which the Me has been shown to be involved.

  8. Dual-afferent sensory input training for voluntary movement after stroke: A pilot randomized controlled study.

    PubMed

    Bae, Seahyun; Kim, Kyung-Yoon

    2017-01-01

    Stimulation through afferent sensory input is necessary to improve voluntary functional movement in stroke patients. Dual-afferent sensory input, which combines electromyography-triggered functional electric stimulation (ETFES) and action observation, was investigated to determine its effects on voluntary movements in stroke patients. This study was conducted on 18 patients with left hemiplegia diagnosed between 6 and 24 months prior. The 9 subjects in the dual-afferent sensory input (DASI) group underwent ETFES with action observation training for 4 weeks (20 min/d, 5 d/wk), while the 9 control group subjects underwent functional electric stimulation (FES) for the same duration. The outcome measures were the movement-related cortical potential (MRCP), H-reflex, electromyography (EMG), and balance. The control and DASI groups showed significant increases in MRCP, muscle activity, and balance, while H-reflex was significantly decreased. MRCP and balance showed significant differences between DASI and control groups. DASI stimulates voluntary movement in patients, causes rapid activation of the cerebral cortex, and reduces excessive excitation of spinal motor neurons. Therefore, DASI, which stimulates voluntary movement, has a greater effect on brain activation in stroke patients.

  9. Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

    PubMed Central

    Mangum, Tyler S.; Sidhu, Simranjit K.; Weavil, Joshua C.; Hureau, Thomas J.; Jessop, Jacob E.; Bledsoe, Amber D.; Richardson, Russell S.; Amann, Markus

    2016-01-01

    Key points The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise‐induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle.Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive locomotor muscle afferents during a 5 km cycling time trial.The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural ‘drive’ to working locomotor muscle and limits the exercise‐induced intramuscular metabolic perturbation.Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance. Abstract To investigate the role of metabo‐ and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise‐induced changes in intramuscular metabolites were determined using liquid and gas chromatography‐mass spectrometry. Quadriceps fatigue was quantified by pre‐ to post‐exercise changes in potentiated quadriceps twitch torque (ΔQTsingle) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial

  10. EFFECTS OF METHYLMERCURY ON SPINAL CORD AFFERENTS AND EFFERENTS—A REVIEW

    PubMed Central

    Colón-Rodríguez, Alexandra; Hannon, Heidi E.; Atchison, William D.

    2017-01-01

    Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRPs, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels. PMID:28041893

  11. Chicken (Gallus domesticus) inner ear afferents

    NASA Technical Reports Server (NTRS)

    Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.

    1998-01-01

    Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

  12. Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle afferent DRG neurons.

    PubMed

    Lin, Yi-Wen; Chen, Chih-Cheng

    2015-01-01

    Muscle afferent neurons that express transient receptor potential vanilloid type I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle nociceptors plays an important role in the acid-induced hyperalgesic priming and the development of chronic hyperalgesia in a mouse model of fibromyalgia. To understand the electrophysiological properties of the TRPV1-expressing muscle afferent neurons, we used whole-cell patch clamp recording to study the acid responsiveness and action potential (AP) configuration of capsaicin-sensitive neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size, resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and acid-induced current (I acid), as well as capsaicin-induced current (I cap). TRPV1-expressing neurons were all acid-sensitive and could be divided into two acid-sensitive groups depending on an acid-induced sustained current (type I) or an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing neurons were distinguishable from type II TRPV1-expressing neurons in AP overshoot, after-hyperpolarization duration, and all I acid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and I cap parameters. These differential biophysical properties of TRPV1-expressing neurons might partially annotate their different roles involved in the development and maintenance of chronic muscle pain.

  13. Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse.

    PubMed

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2017-09-01

    The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli. © 2017 Wiley Periodicals, Inc.

  14. Effect of Microgravity on Afferent Innervation

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Presentations and publications are: (1) an audiovisual summary web presentation on results from SLM-MIR avian experiments. A color presentation summarizing results from the SLM-MIR and STS-29 avian experiments; (2) color threshold and ratio of S 100B MAP5, NF68/200, GABA and GAD; (3) chicken (Gallus domesticus) inner ear afferents; (4) microgravity in the STS-29 Space Shuttle Discovery affected the vestibular system of chick embryos; (5) expression of S 100B in sensory and secretory cells of the vertebrate inner ear; (6) otoconia biogenesis, phylogeny, composition and functional attributes;(7) the glycan keratin sulfate in inner ear crystals; (8) elliptical-P cells in the avian perilymphatic interface of the tegmentum vasculosum; and (9) LAMP2c and S100B upregulation in brain stem after VIIIth nerve deafferentation.

  15. Dual Innervation of Neonatal Merkel Cells in Mouse Touch Domes

    PubMed Central

    Luo, Wenqin

    2014-01-01

    Merkel cell-neurite complexes are specialized mechanosensory end organs that mediate discriminative touch sensation. It is well established that type I slowly adapting (SAI) mechanoreceptors, which express neural filament heavy chain (NFH), innervate Merkel cells. It was previously shown that neurotrophic factor NT3 and its receptor TrkC play crucial roles in controlling touch dome Merkel cell innervation of NFH+ fibers. In addition, nerve fibers expressing another neurotrophic tyrosine receptor kinase (NTRK), Ret, innervate touch dome Merkel cells as well. However, the relationship between afferents responsive to NT3/TrkC signaling and those expressing Ret is unclear. It is also controversial if these Ret+ fibers belong to the early or late Ret+ DRG neurons, which are defined based on the co-expression and developmental dependence of TrkA. To address these questions, we genetically traced Ret+ and TrkC+ fibers and analyzed their developmental dependence on TrkA. We found that Merkel cells in neonatal mouse touch domes receive innervation of two types of fibers: one group is Ret+, while the other subset expresses TrkC and NFH. In addition, Ret+ fibers depend on TrkA for their survival and normal innervation whereas NFH+ Merkel cell innervating fibers are almost unaltered in TrkA mutant mice, supporting that Ret+ and NFH+/TrkC+ afferents are two distinct groups. Ret signaling, on the other hand, plays a minor role for the innervation of neonatal touch domes. In contrast, Merkel cells in the glabrous skin are mainly contacted by NFH+/TrkC+ afferents. Taken together, our results suggest that neonatal Merkel cells around hair follicles receive dual innervation while Merkel cells in the glabrous skin are mainly innervated by only SAI mechanoreceptors. In addition, our results suggest that neonatal Ret+ Merkel cell innervating fibers most likely belong to the late but not early Ret+ DRG neurons. PMID:24637732

  16. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

    PubMed Central

    Ballesteros, Kristen A; Sikorski, Angela; Orfila, James E; Martinez, Joe L

    2012-01-01

    Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA) receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP) in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3). We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3) to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA), or 3-[(R)-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP). Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals anesthetized with isoflurane compared to those anesthetized with sodium pentobarbital. The results suggest that isoflurane may affect amplitude through activation of GABAA receptors or mechanisms important to LTP in CA3 afferent fibers. PMID:23204857

  17. Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition

    PubMed Central

    Meng, Hui; Blázquez, Pablo M; Dickman, J David; Angelaki, Dora E

    2014-01-01

    Abstract A functional role of the cerebellar nodulus and ventral uvula (lobules X and IXc,d of the vermis) for vestibular processing has been strongly suggested by direct reciprocal connections with the vestibular nuclei, as well as direct vestibular afferent inputs as mossy fibres. Here we have explored the types of neurons in the macaque vestibular nuclei targeted by nodulus/ventral uvula inhibition using orthodromic identification from the caudal vermis. We found that all nodulus-target neurons are tuned to vestibular stimuli, and most are insensitive to eye movements. Such non-eye-movement neurons are thought to project to vestibulo-spinal and/or thalamo-cortical pathways. Less than 20% of nodulus-target neurons were sensitive to eye movements, suggesting that the caudal vermis can also directly influence vestibulo-ocular pathways. In general, response properties of nodulus-target neurons were diverse, spanning the whole continuum previously described in the vestibular nuclei. Most nodulus-target cells responded to both rotation and translation stimuli and only a few were selectively tuned to translation motion only. Other neurons were sensitive to net linear acceleration, similar to otolith afferents. These results demonstrate that, unlike the flocculus and ventral paraflocculus which target a particular cell group, nodulus/ventral uvula inhibition targets a large diversity of cell types in the vestibular nuclei, consistent with a broad functional significance contributing to vestibulo-ocular, vestibulo-thalamic and vestibulo-spinal pathways. PMID:24127616

  18. Presynaptic control of transmission along the pathway mediating disynaptic reciprocal inhibition in the cat

    PubMed Central

    Enríquez-Denton, M; Nielsen, J; Perreault, M-C; Morita, H; Petersen, N; Hultborn, H

    2000-01-01

    In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of antagonist motor nerves were depressed for at least 150 ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and ankle extensor (5T) nerves. The aim of the present study was to investigate the possibility that this depression is caused by presynaptic inhibitory mechanisms acting at the terminals of group I afferent fibres projecting to the Ia inhibitory interneurones and/or the terminals of these interneurones to the target motoneurones. Conditioning stimulation of flexor, but not ankle extensor, nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This depression lasted between 200 and 700 ms and was not accompanied by a depression of the monosynaptic EPSPs evoked by stimulation of descending pathways. These results suggest that flexor, but not ankle extensor, group I afferent fibres can modulate sensory transmission at the synapse between Ia afferent fibres and Ia inhibitory interneurones. Conditioning stimulation of flexor muscle nerves, extensor muscle nerves and cutaneous nerves produced a long-lasting increase in excitability of the terminals of the Ia inhibitory interneurones. The increase in the excitability of the terminals was not secondary to an electrotonic spread of synaptic excitation at the soma. Indeed, concomitant with the excitability increase of the terminals there were signs of synaptic inhibition in the soma. The unitary IPSPs induced in target motoneurones following the spike activity of single Ia inhibitory interneurones were depressed by conditioning stimulation of muscle and cutaneous nerves. Since the conditioning stimulation also evoked compound IPSPs in those motoneurones, a firm conclusion as to whether unitary IPSP depression involved presynaptic inhibitory mechanism of the terminals of the interneurones could

  19. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

    PubMed

    Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

    2013-01-15

    Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

  20. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    PubMed

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  1. The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity.

    PubMed

    Mrachacz-Kersting, N; Voigt, M; Stevenson, A J T; Aliakbaryhosseinabadi, S; Jiang, N; Dremstrup, K; Farina, D

    2017-11-01

    A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCI FES and BCI passive ) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20Hz, intensity: 8-35mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCI FES and BCI passive led to significant increases in the excitability of the cortical projections to TA (F (2,22) =4.44, p=0.024) without any concomitant changes at the spinal level. These effects were still present 30min after the cessation of both interventions

  2. Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

    PubMed

    Fuente Mora, Cristina; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

    2015-11-01

    What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P < 0.0001) and additional signs of sympathetic activation, including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube

  3. The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

    PubMed

    Kadekawa, Katsumi; Majima, Tsuyoshi; Shimizu, Takahiro; Wada, Naoki; de Groat, William C; Kanai, Anthony J; Goto, Momokazu; Yoshiyama, Mitsuharu; Sugaya, Kimio; Yoshimura, Naoki

    2017-09-01

    We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1 ) spinal intact (SI)-control, 2 ) SI-capsaicin pretreatment (Cap), 3 ) SCI-control, and 4 ) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice. Copyright © 2017 the American Physiological Society.

  4. Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

    PubMed Central

    Foss, Jason D.; Fink, Gregory D.

    2015-01-01

    Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

  5. A-type potassium channels differentially tune afferent pathways from rat solitary tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus

    PubMed Central

    Bailey, T W; Hermes, S M; Whittier, K L; Aicher, S A; Andresen, M C

    2007-01-01

    The solitary tract nucleus (NTS) conveys visceral information to diverse central networks involved in homeostatic regulation. Although afferent information content arriving at various CNS sites varies substantially, little is known about the contribution of processing within the NTS to these differences. Using retrograde dyes to identify specific NTS projection neurons, we recently reported that solitary tract (ST) afferents directly contact NTS neurons projecting to caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic properties impact information transmission, here we evaluated potassium channel expression and somatodendritic morphology of projection neurons and their relation to afferent information output directed to PVN or CVLM pathways. In slices, tracer-identified projection neurons were classified as directly or indirectly (polysynaptically) coupled to ST afferents by EPSC latency characteristics (directly coupled, jitter < 200 μs). In each neuron, voltage-dependent potassium currents (IK) were evaluated and, in representative neurons, biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS neurons displayed large transient, 4aminopyridine-sensitive, A-type currents (IKA). PVN-projecting neurons had larger cell bodies with more elaborate dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%) triggered action potentials in CVLM-projecting neurons but spike output was uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning hyperpolarization removed IKA inactivation and attenuated ST-evoked spike generation along PVN but not CVLM pathways. Thus, multiple differences in structure, organization, synaptic transmission and ion channel expression tune the overall fidelity of afferent signals that reach these destinations

  6. Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats.

    PubMed

    Raju, Dinesh V; Shah, Deep J; Wright, Terrence M; Hall, Randy A; Smith, Yoland

    2006-11-10

    The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant

  7. Lectin Ulex europaeus agglutinin I specifically labels a subset of primary afferent fibers which project selectively to the superficial dorsal horn of the spinal cord.

    PubMed

    Mori, K

    1986-02-19

    To examine differential carbohydrate expression among different subsets of primary afferent fibers, several fluorescein-isothiocyanate conjugated lectins were used in a histochemical study of the dorsal root ganglion (DRG) and spinal cord of the rabbit. The lectin Ulex europaeus agglutinin I specifically labeled a subset of DRG cells and primary afferent fibers which projected to the superficial laminae of the dorsal horn. These results suggest that specific carbohydrates containing L-fucosyl residue is expressed selectively in small diameter primary afferent fibers which subserve nociception or thermoception.

  8. Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABAB receptors, but not α2 adrenergic receptors

    PubMed Central

    Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G.

    2010-01-01

    GABAB, μ-opioid, and adrenergic α2 receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABAB receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABAB agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α2 adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABAB receptors, but not by α2 receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. PMID:20726886

  9. Correlation between afferent rearrangements and behavioral deficits after local excitotoxic insult in the mammalian vestibule: a rat model of vertigo symptoms.

    PubMed

    Gaboyard-Niay, Sophie; Travo, Cécile; Saleur, Aurélie; Broussy, Audrey; Brugeaud, Aurore; Chabbert, Christian

    2016-10-01

    Damage to inner ear afferent terminals is believed to result in many auditory and vestibular dysfunctions. The sequence of afferent injuries and repair, as well as their correlation with vertigo symptoms, remains poorly documented. In particular, information on the changes that take place at the primary vestibular endings during the first hours following a selective insult is lacking. In the present study, we combined histological analysis with behavioral assessments of vestibular function in a rat model of unilateral vestibular excitotoxic insult. Excitotoxicity resulted in an immediate but transient alteration of the balance function that was resolved within a week. Concomitantly, vestibular primary afferents underwent a sequence of structural changes followed by spontaneous repair. Within the first two hours after the insult, a first phase of pronounced vestibular dysfunction coincided with extensive swelling of afferent terminals. In the next 24 h, a second phase of significant but incomplete reduction of the vestibular dysfunction was accompanied by a resorption of swollen terminals and fiber retraction. Eventually, within 1 week, a third phase of complete balance restoration occurred. The slow and progressive withdrawal of the balance dysfunction correlated with full reconstitution of nerve terminals. Competitive re-innervation by afferent and efferent terminals that mimicked developmental synaptogenesis resulted in full re-afferentation of the sensory epithelia. By deciphering the sequence of structural alterations that occur in the vestibule during selective excitotoxic impairment, this study offers new understanding of how a vestibular insult develops in the vestibule and how it governs the heterogeneity of vertigo symptoms. © 2016. Published by The Company of Biologists Ltd.

  10. Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.

    PubMed

    Bonvini, Sara J; Birrell, Mark A; Grace, Megan S; Maher, Sarah A; Adcock, John J; Wortley, Michael A; Dubuis, Eric; Ching, Yee-Man; Ford, Anthony P; Shala, Fisnik; Miralpeix, Montserrat; Tarrason, Gema; Smith, Jaclyn A; Belvisi, Maria G

    2016-07-01

    Sensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored. We hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung. We used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues. Here we show TRPV4-induced activation of guinea pig airway-specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough. This study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP-mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Endogenous neuropeptide Y depresses the afferent signaling of gastric acid challenge to the mouse brainstem via neuropeptide Y type Y2 and Y4 receptors.

    PubMed

    Wultsch, T; Painsipp, E; Thoeringer, C K; Herzog, H; Sperk, G; Holzer, P

    2005-01-01

    Vagal afferents signal gastric acid challenge to the nucleus tractus solitarii of the rat brainstem. This study investigated whether nucleus tractus solitarii neurons in the mouse also respond to gastric acid challenge and whether this chemonociceptive input is modified by neuropeptide Y acting via neuropeptide Y receptors of type Y2 or Y4. The gastric mucosa of female mice was exposed to different concentrations of HCl or saline, excitation of neurons in the nucleus tractus solitarii visualized by c-Fos immunohistochemistry, gastric emptying deduced from the gastric volume recovery, and gastric lesion formation evaluated by planimetry. Relative to saline, intragastric HCl (0.15-0.35 M) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii in a concentration-dependent manner, inhibited gastric emptying but failed to cause significant hemorrhagic injury in the stomach. Mice in which the Y2 or Y4 receptor gene had been deleted responded to gastric acid challenge with a significantly higher expression of c-Fos in the nucleus tractus solitarii, the increases amounting to 39 and 31%, respectively. The HCl-induced inhibition of gastric emptying was not altered by deletion of the Y2 or Y4 receptor gene. BIIE0246 ((S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e] azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide; 0.03 mmol/kg s.c.), a Y2 receptor antagonist which does not cross the blood-brain barrier, did not modify the c-Fos response to gastric acid challenge. The Y2 receptor agonist peptide YY-(3-36) (0.1 mg/kg intraperitoneally) likewise failed to alter the gastric HCl-evoked expression of c-Fos in the nucleus tractus solitarii. BIIE0246, however, prevented the effect of peptide YY-(3-36) to inhibit gastric acid secretion as deduced from measurement of intragastric pH. The current data indicate that gastric challenge with acid

  12. Kinesthetic perception based on integration of motor imagery and afferent inputs from antagonistic muscles with tendon vibration.

    PubMed

    Shibata, E; Kaneko, F

    2013-04-29

    The perceptual integration of afferent inputs from two antagonistic muscles, or the perceptual integration of afferent input and motor imagery are related to the generation of a kinesthetic sensation. However, it has not been clarified how, or indeed whether, a kinesthetic perception would be generated by motor imagery if afferent inputs from two antagonistic muscles were simultaneously induced by tendon vibration. The purpose of this study was to investigate how a kinesthetic perception would be generated by motor imagery during co-vibration of the two antagonistic muscles at the same frequency. Healthy subjects participated in this experiment. Illusory movement was evoked by tendon vibration. Next, the subjects imaged wrist flexion movement simultaneously with tendon vibration. Wrist flexor and extensor muscles were vibrated according to 4 patterns such that the difference between the two vibration frequencies was zero. After each trial, the perceived movement sensations were quantified on the basis of the velocity and direction of the ipsilateral hand-tracking movements. When the difference in frequency applied to the wrist flexor and the extensor was 0Hz, no subjects perceived movements without motor imagery. However, during motor imagery, the flexion velocity of the perceived movement was higher than the flexion velocity without motor imagery. This study clarified that the afferent inputs from the muscle spindle interact with motor imagery, to evoke a kinesthetic perception, even when the difference in frequency applied to the wrist flexor and extensor was 0Hz. Furthermore, the kinesthetic perception resulting from integrations of vibration and motor imagery increased depending on the vibration frequency to the two antagonistic muscles. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    PubMed Central

    Grey, Michael J; Ladouceur, Michel; Andersen, Jacob B; Nielsen, Jens Bo; Sinkjær, Thomas

    2001-01-01

    The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h−1 with the left ankle attached to a portable stretching device. The soleus stretch reflex was elicited by applying small amplitude (∼8 deg) dorsiflexion perturbations 200 ms after heel contact. Short and medium latency responses were observed with latencies of 55 ± 5 and 78 ± 6 ms, respectively. The short latency response was velocity sensitive (P < 0.001), while the medium latency response was not (P = 0.725). Nerve cooling increased the delay of the medium latency component to a greater extent than that of the short latency component (P < 0.005). Ischaemia strongly decreased the short latency component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). Two hours after the ingestion of tizanidine, an α2-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P = 0.007), whereas the short latency component was unchanged (P = 0.653). An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. Our results support the hypothesis that, during walking the medium latency component of the stretch reflex resulting from an unexpected perturbation is contributed to by group II muscle afferents. PMID:11483721

  14. Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats.

    PubMed Central

    Grimwood, P D; Appenteng, K; Curtis, J C

    1992-01-01

    1. Our aim has been to quantify the monosynaptic connections of trigeminal interneurones and spindle afferents onto jaw-elevator motoneurones as a step towards identifying common features in organization of monosynaptic inputs onto motoneurones. We have used the intracellular variant of the spike-triggered averaging method to examine the connections of single identified trigeminal interneurones and jaw-elevator muscle spindle afferents onto single jaw-elevator motoneurones. The interneurones examined lay in the region immediately caudal to the trigeminal motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Ten EPSPs and eight IPSPs were obtained from examining the connections of seventeen interneurones to thirty-six motoneurones, suggesting a functional connectivity of 50% for individual interneurones onto elevator motoneurones. Fourteen EPSPs were obtained from examining the connections of thirteen spindle afferents onto twenty-seven motoneurones, giving a functional connectivity of 52% for individual spindle afferents onto elevator motoneurones. The amplitudes of the EPSPs elicited by interneurones ranged from 7-48 microV (mean = 17, S.D. = 12.5, n = 10) and from 7 to 289 microV (mean = 64, S.D. = 76.0, n = 14) for the spindle-mediated EPSPs; the difference in the two means was not significant (P = 0.07). 3. However, the amplitude of averaged responses obtained by signal averaging methods are dependent on the assumption that the postsynaptic response occurs following every impulse in the presynaptic neurone. We therefore estimated the percentage of sweeps which contained EPSPs triggered by the presynaptic neurone under study. In essence the method used consisted of visual inspection of the individual sweeps comprising an average in order to assess the occurrence of EPSPs within six separate time windows, each of duration +/- 0.3 ms. Five windows were placed at randomly selected times on

  15. AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent arterioles.

    PubMed

    Patzak, Andreas; Lai, En Y; Mrowka, Ralf; Steege, Andreas; Persson, Pontus B; Persson, A Erik G

    2004-11-01

    Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles (Af) of mice. Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR). Ang II reduced luminal diameters dose dependently (67.3 +/- 6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7) mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6, P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R. The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.

  16. Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat.

    PubMed

    Clark, F J; Matthews, P B; Muir, R B

    1981-02-01

    1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor.2. When the amplitude of vibration was 50 mum, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 mum vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut.3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 mum vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 mum vibration; at the same time the reflex tension increased.4. Additional, indirect evidence favouring widespread security of Ia driving by 50 mum vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action.5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general

  17. Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat

    PubMed Central

    Clark, F. J.; Matthews, P. B. C.; Muir, R. B.

    1981-01-01

    1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor. 2. When the amplitude of vibration was 50 μm, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 μm vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut. 3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 μm vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 μm vibration; at the same time the reflex tension increased. 4. Additional, indirect evidence favouring widespread security of Ia driving by 50 μm vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action. 5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general

  18. Neuropeotide Y changes the excitability of fine afferent units in the rat knee joint

    PubMed Central

    Just, Stefan; Heppelmann, Bernd

    2001-01-01

    The aim of the present study was to examine the effects of the sympathetic co-transmitter Neuropeotide Y on primary afferent nerve fibres of the rat knee joint. The responses to passive joint rotations at defined torque were recorded from 41 slowly conducting afferent nerve fibres (0.9 – 18.8 m s−1) innervating the knee joint capsule. About 70% of the joint afferents were significantly affected in their mechanosensitivity by topical application of Neuropeptide Y. Significant effects occurred at a concentration of 10 nM. Decreased mechanosensitivity was observed in about 40% of nerve fibres, whereas 30% of the units increased the mechanosensitivity. In addition, in about 35% of the fibres resting activity was induced or increased. Neither the conduction velocity nor the mechanical threshold of the units correlated with the described effects of Neuropeptide Y. NPY(13 – 36), a specific Y2-receptor agonist, only modulated the mechanosensitivity, with no effect on the resting activity. The effects on the mechanosensitivity were similar to Neuropeptide Y, i.e. increase and decrease of the response. Studies with the Y1-agonist (Leu31, Pro34)-NPY showed that activation of the Y1-receptor predominantly resulted in an enhanced mechanosensitivity and an induction or increase of a resting activity. The opposite effect was observed by application of BIBP 3226 BS, a Y1-receptor antagonist. In conclusion, these data indicate that Neuropeptide Y affects the excitability of sensory nerve fibre endings. PMID:11159723

  19. Dopaminergic Presynaptic Modulation of Nigral Afferents: Its Role in the Generation of Recurrent Bursting in Substantia Nigra Pars Reticulata Neurons

    PubMed Central

    de Jesús Aceves, José; Rueda-Orozco, Pavel E.; Hernández, Ricardo; Plata, Víctor; Ibañez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, José

    2011-01-01

    Previous work has shown the functions associated with activation of dopamine presynaptic receptors in some substantia nigra pars reticulata (SNr) afferents: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D1-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D1- and D2-class receptors where D1-class receptor activation enhances and D2-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D2-class receptors (D3 and D4 types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D1-class agonists was found on pallidonigral synapses. In contrast, administration of D1-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D3 and D4 type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D1- and D2-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism. PMID:21347219

  20. Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

    PubMed

    Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

    2018-04-20

    Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P < 0.05). Four of seven animals exhibited apneas of ≥20 sec requiring

  1. Feedforward inhibition and synaptic scaling--two sides of the same coin?

    PubMed

    Keck, Christian; Savin, Cristina; Lücke, Jörg

    2012-01-01

    Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing.

  2. Plasticity of cortical inhibition in dystonia is impaired after motor learning and Paired-Associative Stimulation

    PubMed Central

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-01-01

    Summary Artificial induction of plasticity by paired associative stimulation (PAS) in healthy subjects (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory ones. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced LTP-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.“ PMID:22429246

  3. MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

    PubMed

    Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

    2012-06-01

    The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Developmental Programming: Reproductive Endocrinopathies in the Adult Female Sheep After Prenatal Testosterone Treatment Are Reflected in Altered Ontogeny of GnRH Afferents

    PubMed Central

    Hershey, John; Mytinger, Andrea; Foster, Douglas L.; Padmanabhan, Vasantha

    2011-01-01

    The GnRH system represents a useful model of long-term neural plasticity. An unexplored facet of this plasticity relates to the ontogeny of GnRH neural afferents during critical periods when the hypothalamic-pituitary-gonadal axis is highly susceptible to perturbation by sex steroids. Sheep treated with testosterone (T) in utero exhibit profound reproductive neuroendocrine dysfunctions during their lifespan. The current study tested the hypothesis that these changes are associated with alterations in the normal ontogeny of GnRH afferents and glial associations. Adult pregnant sheep (n = 50) were treated with vehicle [control (CONT)] or T daily from gestational day (GD)30 to GD90. CONT and T fetuses (n = 4–6/treatment per age group) were removed by cesarean section on GD90 and GD140 and the brains frozen at −80°C. Brains were also collected from CONT and T females at 20–23 wk (prepubertal), 10 months (normal onset of puberty and oligo-anovulation), and 21 months (oligo-anovulation in T females). Tissue was analyzed for GnRH immunoreactivity (ir), total GnRH afferents (Synapsin-I ir), glutamate [vesicular glutamate transporter-2 (VGLUT2)-ir], and γ-aminobutyric acid [GABA, vesicular GABA transporter (VGAT)-ir] afferents and glial associations (glial fibrillary acidic protein-ir) with GnRH neurons using optical sectioning techniques. The results revealed that: 1) GnRH soma size was slightly reduced by T, 2) the total (Synapsin-I) GnRH afferents onto both somas and dendrites increased significantly with age and was reduced by T, 3) numbers of both VGAT and VGLUT inputs increased significantly with age and were also reduced by T, and 4) glial associations with GnRH neurons were reduced (<10%) by T. Together, these findings reveal a previously unknown developmental plasticity in the GnRH system of the sheep. The altered developmental trajectory of GnRH afferents after T reinforces the notion that prenatal programming plays an important role in the normal

  5. Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

    PubMed

    Chittajallu, R; Wester, J C; Craig, M T; Barksdale, E; Yuan, X Q; Akgül, G; Fang, C; Collins, D; Hunt, S; Pelkey, K A; McBain, C J

    2017-07-28

    Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

  6. Role of afferent input and mechanical load for size regulation of rat soleus muscle

    NASA Astrophysics Data System (ADS)

    Kawano, Fuminori; Matsuka, Yoshikazu; Oke, Yoshihiko; Higo, Yoko; Terada, Masahiro; Umemoto, Shiori; Kawabe, Naoko; Wang, Xiao Dong; Shinoda, Yo; Lan, Yong Bo; Fukuda, Hiroyuki; Ohmi, Shinobu; Ohira, Yoshinobu

    2005-08-01

    Effects of deafferentation on the phosphorylation of ribosomal protein S6 (S6), 27 kDa heat shock protein (HSP27) and extracellular signal-regulated kinase (ERK) 1/2 were studied in rat soleus muscle. Adult male Wistar rats were randomly separated into the pre- and post- experimental control, functionally overloaded (FO), sham-operated, deafferentated (DA), FO+DA, and hindlimb-unloaded (U) groups. The distal tendons of left plantaris and gastrocnemius muscles were transected in the FO rats. The left dorsal roots of the spinal cord at the L4-5 segmental levels were transected in the DA rats. The rats in U were tail-suspended. The sampling of the soleus muscle was performed 2 weeks after the treatments shown above. The cytoplasmic fraction of the soleus muscle homogenate was used for the quantitative analyses of the phosphorylation levels of S6, HSP27, and ERK 1/2. The phosphorylation levels of these proteins were up-regulated by FO. On the contrary, the phosphorylation of all of these proteins was down-regulated by U and DA. Further, the FO-related increase of the protein phosphorylation was inhibited by additional treatment with DA. These results indicated that the afferent feedback plays crucial roles in the intramuscular regulation of the soleus muscle mass.

  7. Stability of Kinesthetic Perception in Efferent-Afferent Spaces: The Concept of Iso-perceptual Manifold.

    PubMed

    Latash, Mark L

    2018-02-21

    The main goal of this paper is to introduce the concept of iso-perceptual manifold for perception of body configuration and related variables (kinesthetic perception) and to discuss its relation to the equilibrium-point hypothesis and the concepts of reference coordinate and uncontrolled manifold. Hierarchical control of action is postulated with abundant transformations between sets of spatial reference coordinates for salient effectors at different levels. Iso-perceptual manifold is defined in the combined space of afferent and efferent variables as the subspace corresponding to a stable percept. Examples of motion along an iso-perceptual manifold (perceptually equivalent motion) are considered during various natural actions. Some combinations of afferent and efferent signals, in particular those implying a violation of body's integrity, give rise to variable percepts by artificial projection onto iso-perceptual manifolds. This framework is used to interpret unusual features of vibration-induced kinesthetic illusions and to predict new illusions not yet reported in the literature. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa.

    PubMed

    Pabst, M A; Schöninkle, E; Holzer, P

    1993-07-01

    Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa.

  9. Age-related influence of vision and proprioception on Ia presynaptic inhibition in soleus muscle during upright stance

    PubMed Central

    Baudry, Stéphane; Duchateau, Jacques

    2012-01-01

    This study investigated the modulation of Ia afferent input in young and elderly adults during quiet upright stance in normal and modified visual and proprioceptive conditions. The surface EMG of leg muscles, recruitment curve of the soleus (SOL) Hoffmann (H) reflex and presynaptic inhibition of Ia afferents from SOL, assessed with the D1 inhibition and single motor unit methods, were recorded when young and elderly adults stood with eyes open or closed on two surfaces (rigid vs. foam) placed over a force platform. The results showed that elderly adults had a longer path length for the centre of pressure and larger antero-posterior body sway across balance conditions (P < 0.05). Muscle EMG activities were greater in elderly compared with young adults (P < 0.05), whereas the Hmax expressed as a percentage of the Hmax was lower (P = 0.048) in elderly (38 ± 16%) than young adults (58 ± 16%). The conditioned H reflex/test H reflex ratio (D1 inhibition method) increased with eye closure and when standing on foam (P < 0.05), with greater increases for elderly adults (P = 0.019). These changes were accompanied by a reduced peak motor unit discharge probability when standing on rigid and foam surfaces (P ≤ 0.001), with a greater effect for elderly adults (P = 0.026). Based on these latter results, the increased conditioned H reflex/test H reflex ratio in similar sensory conditions is likely to reflect occlusion at the level of presynaptic inhibitory interneurones. Together, these findings indicate that elderly adults exhibit greater modulation of Ia presynaptic inhibition than young adults with variation in the sensory conditions during upright standing. PMID:22946095

  10. Losartan increases NO release in afferent arterioles during regression of L-NAME-induced renal damage.

    PubMed

    Helle, Frank; Iversen, Bjarne M; Chatziantoniou, Christos

    2010-05-01

    Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of N(G)-nitro-L-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10(-7) M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10(-9) M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10(-7) M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10(-9), 10(-8), 10(-7) M) were enhanced by NOS inhibition and blunted by exogenous NO (10(-2) mM S-nitroso-N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial

  11. Histamine excites groups III and IV afferents from the cat knee joint depending on their resting activity.

    PubMed

    Herbert, M K; Just, H; Schmidt, R F

    2001-06-08

    The effect of histamine on the sensory activity of primary afferents was studied in normal and acutely inflamed cat knee joints. A subpopulation of groups III and IV articular afferents could be activated by close-arterial bolus injections of histamine: units with a high resting activity (about 100/min) were particular sensitive to histamine and were excited even by 3.3 fg histamine. The lower the resting discharges of groups III and IV units both from normal and acutely inflamed joints, the higher the dose of histamine (up to 3.3 or 33 microg) necessary to excite the nerve fibres. Thirty-seven of 39 units without any resting activity were completely insensitive to histamine. In contrast to its clear excitatory effect, histamine caused only minor changes in the responses to joint movements. Movement-evoked activity remained unchanged in 22 of 28 units, 1 unit was sensitized and 5 units showed reduced activity after histamine (3.3 microg). The present results support the notion that histamine may participate in the mediation of pain from injured or inflamed tissue. It is remarkable that histamine has a profound excitatory action on a proportion of both groups III and IV articular afferents without changing their sensitivity to joint movements.

  12. [Cartography and geographical spread of the adventitious species of brome (Bromus spp.) among cereals in the Sais area of Morocco].

    PubMed

    Hamal, A; Benbella, M; Rzozi, S B; Bouhache, M; Msatef, Y

    2001-01-01

    Bromus spp is causing serious problems in wheat in the Sais area. However, the damage of this weed varies from one region to another according to the agro-climatic conditions and crop systems. The characterization of the infestation level in each situation is a prerequisite to develop a control strategy adapted to each environment. This study was undertaken in order to determine the infestation level and geographical spread of the weedy brome (Bromus spp) on wheat in Sais following crop systems and pedo-climatic conditions. The results obtained during two consecutive years (1998-99 and 1999-2000) revealed that ripgut brome (Bromus rigidus Roth.) was the most dominant species in wheat fields in the surveyed regions, followed by B. rubens L., B. sterilis L., B. madritensis L. and B. mollus L. Among, 18 regions and 100 infested wheat fields, 16.67% of fields were slightly infested (Plant density of Bromus (Dbr < 90 plants/m2, 61.11% were moderately infested (90 < Dbr < 290 plants/m2) and 22.22% were highly infested (Dbr > 400 plants/m2). The maximum relative frequency was obtained with Bromus rigidus (47.15%) and the coverage was 40.43%. But, for B.rubens, B. madritensis and B. sterilis, the relative frequencies were respectively 31.42; 26 and 15% and their coverages were respectively 28.9, 20.4 and 12.5%.

  13. Concurrent gradients of ribbon volume and AMPA-receptor patch volume in cochlear afferent synapses on gerbil inner hair cells.

    PubMed

    Zhang, Lichun; Engler, Sina; Koepcke, Lena; Steenken, Friederike; Köppl, Christine

    2018-07-01

    The Mongolian gerbil is a classic animal model for age-related hearing loss. As a prerequisite for studying age-related changes, we characterized cochlear afferent synaptic morphology in young adult gerbils, using immunolabeling and quantitative analysis of confocal microscopic images. Cochlear wholemounts were triple-labeled with a hair-cell marker, a marker of presynaptic ribbons, and a marker of postsynaptic AMPA-type glutamate receptors. Seven cochlear positions covering an equivalent frequency range from 0.5 - 32 kHz were evaluated. The spatial positions of synapses were determined in a coordinate system with reference to their individual inner hair cell. Synapse numbers confirmed previous reports for gerbils (on average, 20-22 afferents per inner hair cell). The volumes of presynaptic ribbons and postsynaptic glutamate receptor patches were positively correlated: larger ribbons associated with larger receptor patches and smaller ribbons with smaller patches. Furthermore, the volumes of both presynaptic ribbons and postsynaptic receptor patches co-varied along the modiolar-pillar and the longitudinal axes of their hair cell. The gradients in ribbon volume are consistent with previous findings in cat, guinea pig, mouse and rat and further support a role in differentiating the physiological properties of type I afferents. However, the positive correlation between the volumes of pre- and postsynaptic elements in the gerbil is different to the opposing gradients found in the mouse, suggesting species-specific differences in the postsynaptic AMPA receptors that are unrelated to the fundamental classes of type I afferents. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Transmission between type II hair cells and bouton afferents in the turtle posterior crista.

    PubMed

    Holt, Joseph C; Xue, Jin-Tang; Brichta, Alan M; Goldberg, Jay M

    2006-01-01

    Synaptic activity was recorded with sharp microelectrodes during rest and during 0.3-Hz sinusoidal stimulation from bouton afferents identified by their efferent-mediated inhibitory responses. A glutamate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased quantal size (qsize) while lowering external Ca(2+) decreased quantal rate (qrate). Miniature excitatory postsynaptic potentials (mEPSPs) had effective durations (qdur) of 3.5-5 ms. Their timing was consistent with Poisson statistics. Mean qsizes ranged in different units from 0.25 to 0.73 mV and mean qrates from 200 to 1,500/s; there was an inverse relation across the afferent population between qrate and qsize. qsize distributions were consistent with the independent release of variable-sized quanta. Channel noise, measured during AMPA-induced depolarizations, was small compared with quantal noise. Excitatory responses were larger than inhibitory responses. Peak qrates, which could approach 3,000/s, led peak excitatory mechanical stimulation by 40 degrees . Quantal parameters varied with stimulation phase with qdur and qsize being maximal during inhibitory stimulation. Voltage modulation (vmod) was in phase with qrate and had a peak depolarization of 1.5-3 mV. On average, 80% of vmod was accounted for by quantal activity; the remaining 20% was a nonquantal component that persisted in the absence of quantal activity. The extracellular accumulation of glutamate and K(+) are potential sources of nonquantal transmission and may provide a basis for the inverse relation between qrate and qsize. Comparison of the phases of synaptic and spike activity suggests that both presynaptic and postsynaptic mechanisms contribute to variations across afferents in the timing of spikes during sinusoidal stimulation.

  15. Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs

    PubMed Central

    Mazzone, Stuart B; Mori, Nanako; Canning, Brendan J

    2005-01-01

    Cough initiated from the trachea and larynx in anaesthetized guinea-pigs is mediated by capsaicin-insensitive, mechanically sensitive vagal afferent neurones. Tachykinin-containing, capsaicin-sensitive C-fibres also innervate the airways and have been implicated in the cough reflex. Capsaicin-sensitive nerves act centrally and synergistically to modify reflex bronchospasm initiated by airway mechanoreceptor stimulation. The hypothesis that polymodal mechanoreceptors and capsaicin-sensitive afferent nerves similarly interact centrally to regulate coughing was addressed in this study. Cough was evoked from the tracheal mucosa either electrically (16 Hz, 10 s trains, 1–10 V) or by citric acid (0.001–2 m). Neither capsaicin nor bradykinin evoked a cough when applied to the trachea of anaesthetized guinea-pigs, but they substantially reduced the electrical threshold for initiating the cough reflex. The TRPV1 receptor antagonist capsazepine prevented the increased cough sensitivity induced by capsaicin. These effects of topically applied capsaicin and bradykinin were not due to interactions between afferent nerve subtypes within the tracheal wall or a direct effect on the cough receptors, as they were mimicked by nebulizing 1 mg ml−1 bradykinin into the lower airways and by microinjecting 0.5 nmol capsaicin into nucleus of the solitary tract (nTS). Citric acid-induced coughing was also potentiated by inhalation of bradykinin. The effects of tracheal capsaicin challenge on cough were mimicked by microinjecting substance P (0.5–5 nmol) into the nTS and prevented by intracerebroventricular administration (20 nmol h−1) of the neurokinin receptor antagonists CP99994 or SB223412. Tracheal application of these antagonists was without effect. C-fibre activation may thus sensitize the cough reflex via central mechanisms. PMID:16051625

  16. Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABA(B) receptors, but not α2 adrenergic receptors.

    PubMed

    Zhang, Guohua; Chen, Wenling; Marvizón, Juan Carlos G

    2010-09-01

    GABA(B) , μ-opioid and adrenergic α(2) receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABA(B) receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high-frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABA(B) agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low-frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α(2) adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low-frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABA(B) receptors, but not by α(2) receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

  17. Duodenal afferent input converges onto T9-T10 spinal neurons responding to gastric distension in rats.

    PubMed

    Qin, Chao; Chen, Jiande D Z; Zhang, Jing; Foreman, Robert D

    2007-12-01

    Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Graded gastric distensions (GD, 20, 40, 60 mm Hg, 20 s) were induced by air inflation of a latex balloon surgically placed in the stomach. Graded duodenal distensions (DD, 0.2, 0.4, 0.6 ml, 20 s) were produced by water inflation of a latex balloon placed into the duodenum. Of 70 deeper (depth from dorsal surface of spinal cord: 0.3-1.2 mm) spinal neurons responsive to noxious GD (> or =40 mm Hg), 44(63%) also responded to noxious DD (> or =0.4 ml). Similarly, 13/17 (76%) superficial neurons (depth <0.3 mm) responded to both GD and DD. Of 57 gastroduodenal convergent neurons, 41 (72%) had excitatory and 6 had inhibitory responses to both GD and DD; the remaining neurons exhibited multiple patterns of excitation and inhibition. 43/57 (75%) gastroduodenal convergent neurons had low-threshold (< or =20 mm Hg) responses to GD, whereas 42/57 (74%) of these neurons had high-threshold (> or =0.4 ml) responses to DD. In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the

  18. Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea-pig trachealis.

    PubMed Central

    Canning, B J; Undem, B J

    1994-01-01

    1. We recently described a capsaicin-sensitive vagal pathway mediating non-adrenergic, non-cholinergic (NANC) relaxations of an isolated, innervated rostral guinea-pig tracheal preparation. These afferent fibres are carried by the superior laryngeal nerves and relaxations elicited by their activation are insensitive to autonomic ganglion blockers such as hexamethonium. In the present study this vagal relaxant pathway was further characterized. 2. Relaxations of the trachealis elicited by electrical stimulation of capsaicin-sensitive vagal afferents were mimicked by bath application of capsaicin. Relaxations elicited by both methods were abolished when the tissue between the trachea and the adjacent oesophagus was disrupted. Indeed, separating the trachea from the oesophagus uncovered a contractile effect of capsaicin administration on the trachealis. 3. Capsaicin-induced, oesophagus-dependent relaxations of the trachealis were blocked by pretreatment with the fast sodium channel blocker tetrodotoxin (TTX). By contrast, capsaicin-induced contractions of the trachealis (obtained in the absence of the oesophagus) were unaffected by tetrodotoxin. 4. Substance P, neurokinin A (NKA) and neurokinin B (NKB) also elicited NANC relaxations of precontracted trachealis that were abolished by separating the trachea from the oesophagus or by TTX pretreatment. Like capsaicin, the tachykinins elicited only contractions of the trachealis following TTX pretreatment or separation of the trachea from the adjacent oesophagus. 5. Relaxations elicited by stimulation of the capsaicin-sensitive nerves were unaffected by a concentration of the tachykinin NK2 receptor-selective antagonist, SR 48968, that is selective for NK2 receptor blockade and were not mimicked by the NK2 receptor-selective agonist [beta-Ala8]-NKA(4-10). This suggests that NK2 receptors are not responsible for these relaxations. By contrast, the NK3 receptor-selective agonist, senktide analogue, and the NK1 receptor

  19. Somatotopic organization of primary afferent perikarya of the guinea-pig extraocular muscles in the trigeminal ganglion: a post-mortem DiI-tracing study.

    PubMed

    Aigner, M; Robert Lukas, J; Denk, M; Ziya-Ghazvini, F; Kaider, A; Mayr, R

    2000-04-01

    Apart from the somatotopic organization of the trigeminal ganglion (TG) into the ophthalmic, maxillary and mandibular divisions along the mediolateral axis, there exist further somatotopic organizations within these three divisions. According to literature, the cell organization in the TG and the somatotopy in the brainstem develop together, formed by naturally occurring cell death in the TG. Thus, the somatotopy of the primary afferent trigeminal perikarya is of special interest. The aim of this study was to investigate the location of the primary afferent perikarya of the extraocular muscles (EOMs) in the TG of guinea-pig. The primary afferent perikarya were labeled by post-mortem application of the carbocyanine DiI on the oculomotor nerve branches near their entrance into the single EOMs. The DiI-positive perikarya were found musculo-somatically organized in the ipsilateral ophthalmic part of the TG at a wide range along the dorsoventral axis, expressing an overlap of the representation areas. The primary afferent perikarya of the superior rectus and the superior oblique muscles were mainly localized in the dorsal part of the ganglion while those of the inferior rectus and the inferior oblique muscle mainly in ventral part. The lateral and the medial rectus were predominantly represented in between. An organization along the mediolateral axis of the TG was not observed. Although guinea-pigs lack classical EOM proprioceptors, the somatotopic representation of the extraocular muscle primary afferent perikarya in the TG found in this study is in line with findings in species with well known encapsulated proprioceptors within the EOMs.

  20. Feedforward Inhibition and Synaptic Scaling – Two Sides of the Same Coin?

    PubMed Central

    Lücke, Jörg

    2012-01-01

    Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing. PMID:22457610

  1. Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature

    PubMed Central

    Eisenach, James C.; Ririe, Douglas G.

    2015-01-01

    The ability to distinguish mechanical from thermal input is a critical component of peripheral somatosensory function. Polymodal C fibers respond to both stimuli. However, mechanosensitive, modality-specific fast-conducting tactile and nociceptor afferents theoretically carry information only about mechanical forces independent of the thermal environment. We hypothesize that the thermal environment can nonetheless modulate mechanical force sensibility in fibers that do not respond directly to change in temperature. To study this, fast-conducting mechanosensitive peripheral sensory fibers in male Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 or L4/L5. Neuronal identification was performed using receptive field characteristics and passive and active electrical properties. Neurons responded to mechanical stimuli but failed to generate action potentials in response to changes in temperature alone, except for the tactile mechanical and cold sensitive neurons. Heat and cold ramps were utilized to determine temperature-induced modulation of response to mechanical stimuli. Mechanically evoked electrical activity in non-nociceptive, low-threshold mechanoreceptors (tactile afferents) decreased in response to changes in temperature while mechanically induced activity was increased in nociceptive, fast-conducting, high-threshold mechanoreceptors in response to the same changes in temperature. These data suggest that mechanical activation does not occur in isolation but rather that temperature changes appear to alter mechanical afferent activity and input to the central nervous system in a dynamic fashion. Further studies to understand the psychophysiological implications of thermal modulation of fast-conducting mechanical input to the spinal cord will provide greater insight into the implications of these findings. PMID:26581873

  2. Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters

    PubMed Central

    Goh, Jinzhong J.; Manahan-Vaughan, Denise

    2012-01-01

    Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP) and long-term depression (LTD), it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7, or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression (STD) that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g., 900 pulses given twice at 5 min intervals), or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24 h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g., learning) conditions. PMID:23355815

  3. Mechanisms of inhibition in cat visual cortex.

    PubMed Central

    Berman, N J; Douglas, R J; Martin, K A; Whitteridge, D

    1991-01-01

    1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1804983

  4. Chemoarchitecture and afferent connections of the "olfactostriatum": a specialized vomeronasal structure within the basal ganglia of snakes.

    PubMed

    Martinez-Marcos, Alino; Ubeda-Bañon, Isabel; Lanuza, Enrique; Halpern, Mimi

    2005-01-01

    The olfactostriatum, a portion of the striatal complex of snakes, is the major tertiary vomeronasal structure in the ophidian brain, receiving substantial afferents from the nucleus sphericus, the primary target of accessory olfactory bulb efferents. In the present study, we have characterized the olfactostriatum of garter snakes (Thamnophis sirtalis) on the basis of chemoarchitecture (distribution of serotonin, neuropeptide Y and tyrosine hydroxylase) and hodology (afferent connections). The olfactostriatum is densely immunoreactive for serotonin and neuropeptide Y and shows moderate-to-weak immunoreactivity for tyrosine hydroxylase. In addition to afferents from the nucleus sphericus, the olfactostriatum receives inputs from the dorsal and lateral cortices, nucleus of the accessory olfactory tract, external and dorsolateral amygdalae, dorsomedial thalamic nucleus, ventral tegmental area and raphe nuclei. Double labeling experiments demonstrated that the distribution of serotonin and neuropeptide Y in this area almost completely overlaps the terminal field of projections from the nucleus sphericus. Also, serotonergic and dopaminergic innervation of the olfactostriatum likely arise, respectively, from the raphe nuclei and the ventral tegmental area, whereas local circuit neurons originate the neuropeptide Y immunoreactivity. These results indicate that the olfactostriatum of snakes could be a portion of the nucleus accumbens, with features characteristic of the accumbens shell, devoted to processing vomeronasal information. Comparative data suggest that a similar structure is present in the ventral striatum of amphibians and mammals.

  5. The Increased Sensitivity of Irregular Peripheral Canal and Otolith Vestibular Afferents Optimizes their Encoding of Natural Stimuli

    PubMed Central

    Schneider, Adam D.; Jamali, Mohsen; Carriot, Jerome; Chacron, Maurice J.

    2015-01-01

    Efficient processing of incoming sensory input is essential for an organism's survival. A growing body of evidence suggests that sensory systems have developed coding strategies that are constrained by the statistics of the natural environment. Consequently, it is necessary to first characterize neural responses to natural stimuli to uncover the coding strategies used by a given sensory system. Here we report for the first time the statistics of vestibular rotational and translational stimuli experienced by rhesus monkeys during natural (e.g., walking, grooming) behaviors. We find that these stimuli can reach intensities as high as 1500 deg/s and 8 G. Recordings from afferents during naturalistic rotational and linear motion further revealed strongly nonlinear responses in the form of rectification and saturation, which could not be accurately predicted by traditional linear models of vestibular processing. Accordingly, we used linear–nonlinear cascade models and found that these could accurately predict responses to naturalistic stimuli. Finally, we tested whether the statistics of natural vestibular signals constrain the neural coding strategies used by peripheral afferents. We found that both irregular otolith and semicircular canal afferents, because of their higher sensitivities, were more optimized for processing natural vestibular stimuli as compared with their regular counterparts. Our results therefore provide the first evidence supporting the hypothesis that the neural coding strategies used by the vestibular system are matched to the statistics of natural stimuli. PMID:25855169

  6. Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

    PubMed

    Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

    2012-02-01

    Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.

  7. Plasticity of cortical inhibition in dystonia is impaired after motor learning and paired-associative stimulation.

    PubMed

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-03-01

    Artificial induction of plasticity by paired associative stimulation (PAS) in healthy volunteers (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory networks. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long-interval intracortical inhibition (LICI, reflecting activity of GABA(B) interneurons) and long-latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced long-term potentiation (LTP)-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Physiological regulation of magnocellular neurosecretory cell activity: Integration of intrinsic, local and afferent mechanisms

    PubMed Central

    Brown, Colin H.; Bains, Jaideep S.; Ludwig, Mike; Stern, Javier E.

    2013-01-01

    The hypothalamic supraoptic and paraventricular nucleus contain magnocellular neurosecretory cells (MNCs) that project to the posterior pituitary gland where they secrete either oxytocin or vasopressin (the anti-diuretic hormone) into the circulation. Oxytocin is important for delivery at birth and is essential for milk ejection during suckling. Vasopressin primarily promotes water reabsorption in the kidney to maintain body fluid balance, but also increases vasoconstriction. The profile of oxytocin and vasopressin secretion is principally determined by the pattern of action potentials initiated at the cell bodies. While it has long been known that the activity of MNCs depends upon afferent inputs that relay information on reproductive, osmotic and cardiovascular status, it has recently become clear that activity depends critically on local regulation by glial cells, as well as intrinsic regulation by the MNCs themselves. Here, we provide an overview of recent advances in our understanding of how intrinsic and local extrinsic mechanisms integrate with afferent inputs to generate appropriate physiological regulation of oxytocin and vasopressin MNC activity. PMID:23701531

  9. SAI (Systems Applications, Incorporated) Urban Airshed Model. Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schere, K.L.

    1985-06-01

    This magnetic tape contains the FORTRAN source code, sample input data, and sample output data for the SAI Urban Airshed Model (UAM). The UAM is a 3-dimensional gridded air-quality simulation model that is well suited for predicting the spatial and temporal distribution of photochemical pollutant concentrations in an urban area. The model is based on the equations of conservation of mass for a set of reactive pollutants in a turbulent-flow field. To solve these equations, the UAM uses numerical techniques set in a 3-D finite-difference grid array of cells, each about 1 to 10 kilometers wide and 10 to severalmore » hundred meters deep. As output, the model provides the calculated pollutant concentrations in each cell as a function of time. The chemical species of prime interest included in the UAM simulations are O3, NO, NO/sub 2/ and several organic compounds and classes of compounds. The UAM system contains at its core the Airshed Simulation Program that accesses input data consisting of 10 to 14 files, depending on the program options chosen. Each file is created by a separate data-preparation program. There are 17 programs in the entire UAM system. The services of a qualified dispersion meteorologist, a chemist, and a computer programmer will be necessary to implement and apply the UAM and to interpret the results. Software Description: The program is written in the FORTRAN programming language for implementation on a UNIVAC 1110 computer under the UNIVAC 110 0 operating system level 38R5A. Memory requirement is 80K.« less

  10. Voltage-Gated Calcium Influx Modifies Cholinergic Inhibition of Inner Hair Cells in the Immature Rat Cochlea.

    PubMed

    Zachary, Stephen; Nowak, Nathaniel; Vyas, Pankhuri; Bonanni, Luke; Fuchs, Paul Albert

    2018-06-20

    Until postnatal day (P) 12, inner hair cells of the rat cochlea are invested with both afferent and efferent synaptic connections. With the onset of hearing at P12, the efferent synapses disappear, and afferent (ribbon) synapses operate with greater efficiency. This change coincides with increased expression of voltage-gated potassium channels, the loss of calcium-dependent electrogenesis, and the onset of graded receptor potentials driven by sound. The transient efferent synapses include near-membrane postsynaptic cisterns thought to regulate calcium influx through the hair cell's α9-containing and α10-containing nicotinic acetylcholine receptors. This influx activates small-conductance Ca 2+ -activated K + (SK) channels. Serial-section electron microscopy of inner hair cells from two 9-d-old (male) rat pups revealed many postsynaptic efferent cisterns and presynaptic afferent ribbons whose average minimal separation in five cells ranged from 1.1 to 1.7 μm. Efferent synaptic function was studied in rat pups (age, 7-9 d) of either sex. The duration of these SK channel-mediated IPSCs was increased by enhanced calcium influx through L-type voltage-gated channels, combined with ryanodine-sensitive release from internal stores-presumably the near-membrane postsynaptic cistern. These data support the possibility that inner hair cell calcium electrogenesis modulates the efficacy of efferent inhibition during the maturation of inner hair cell synapses. SIGNIFICANCE STATEMENT Strict calcium buffering is essential for cellular function. This problem is especially acute for compact hair cells where increasing cytoplasmic calcium promotes the opposing functions of closely adjoining afferent and efferent synapses. The near-membrane postsynaptic cistern at efferent synapses segregates synaptic calcium signals by acting as a dynamic calcium store. The hair cell serves as an informative model for synapses with postsynaptic cisterns (C synapses) found in central neurons

  11. Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

    NASA Technical Reports Server (NTRS)

    Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

  12. Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans.

    PubMed

    Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

    2012-02-01

    Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α(2)-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gα(o). In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of 'inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α(2)-adrenoreceptors on afferent nociceptors and stimulatory α(1)-receptors on inhibitory peptidergic interneurons.

  13. Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans

    PubMed Central

    Mills, Holly; Wragg, Rachel; Hapiak, Vera; Castelletto, Michelle; Zahratka, Jeffrey; Harris, Gareth; Summers, Philip; Korchnak, Amanda; Law, Wenjing; Bamber, Bruce; Komuniecki, Richard

    2012-01-01

    Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α2-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gαo. In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of ‘inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α2-adrenoreceptors on afferent nociceptors and stimulatory α1-receptors on inhibitory peptidergic interneurons. PMID:22124329

  14. Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature.

    PubMed

    Boada, M Danilo; Eisenach, James C; Ririe, Douglas G

    2016-01-01

    The ability to distinguish mechanical from thermal input is a critical component of peripheral somatosensory function. Polymodal C fibers respond to both stimuli. However, mechanosensitive, modality-specific fast-conducting tactile and nociceptor afferents theoretically carry information only about mechanical forces independent of the thermal environment. We hypothesize that the thermal environment can nonetheless modulate mechanical force sensibility in fibers that do not respond directly to change in temperature. To study this, fast-conducting mechanosensitive peripheral sensory fibers in male Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 or L4/L5. Neuronal identification was performed using receptive field characteristics and passive and active electrical properties. Neurons responded to mechanical stimuli but failed to generate action potentials in response to changes in temperature alone, except for the tactile mechanical and cold sensitive neurons. Heat and cold ramps were utilized to determine temperature-induced modulation of response to mechanical stimuli. Mechanically evoked electrical activity in non-nociceptive, low-threshold mechanoreceptors (tactile afferents) decreased in response to changes in temperature while mechanically induced activity was increased in nociceptive, fast-conducting, high-threshold mechanoreceptors in response to the same changes in temperature. These data suggest that mechanical activation does not occur in isolation but rather that temperature changes appear to alter mechanical afferent activity and input to the central nervous system in a dynamic fashion. Further studies to understand the psychophysiological implications of thermal modulation of fast-conducting mechanical input to the spinal cord will provide greater insight into the implications of these findings. Copyright © 2016 the American Physiological Society.

  15. [Types of apraxia of the articulation apparatus in afferent motor aphasia].

    PubMed

    Shokhor-Trotskaia, M K

    1977-01-01

    On the basis of the comparative data on physiology and psychology of speech, as well as applied and comparative linguistics, it is known that apraxia of articulation apparatus in patients with afferent motor aphasia is heterogenous. The study of 3 groups of patients with primary apraxia of either a tongue, lips, or pharynx and larynx allowed one to find that in persons whose native language is Russian, written speech, reading and understanding is disturbed to a lesser degree in primary apraxia of glotis and larynx that are not initial phonemoformation organs in the Russian language.

  16. Decreased afferent excitability contributes to synaptic depression during high-frequency stimulation in hippocampal area CA1

    PubMed Central

    Kim, Eunyoung; Owen, Benjamin; Holmes, William R.

    2012-01-01

    Long-term potentiation (LTP) is often induced experimentally by continuous high-frequency afferent stimulation (HFS), typically at 100 Hz for 1 s. Induction of LTP requires postsynaptic depolarization and voltage-dependent calcium influx. Induction is more effective if the same number of stimuli are given as a series of short bursts rather than as continuous HFS, in part because excitatory postsynaptic potentials (EPSPs) become strongly depressed during HFS, reducing postsynaptic depolarization. In this study, we examined mechanisms of EPSP depression during HFS in area CA1 of rat hippocampal brain slices. We tested for presynaptic terminal vesicle depletion by examining minimal stimulation-evoked excitatory postsynaptic currents (EPSCs) during 100-Hz HFS. While transmission failures increased, consistent with vesicle depletion, EPSC latencies also increased during HFS, suggesting a decrease in afferent excitability. Extracellular recordings of Schaffer collateral fiber volleys confirmed a decrease in afferent excitability, with decreased fiber volley amplitudes and increased latencies during HFS. To determine the mechanism responsible for fiber volley changes, we recorded antidromic action potentials in single CA3 pyramidal neurons evoked by stimulating Schaffer collateral axons. During HFS, individual action potentials decreased in amplitude and increased in latency, and these changes were accompanied by a large increase in the probability of action potential failure. Time derivative and phase-plane analyses indicated decreases in both axon initial segment and somato-dendritic components of CA3 neuron action potentials. Our results indicate that decreased presynaptic axon excitability contributes to depression of excitatory synaptic transmission during HFS at synapses between Schaffer collaterals and CA1 pyramidal neurons. PMID:22773781

  17. Caffeinated energy drink intake modulates motor circuits at rest, before and after a movement.

    PubMed

    Concerto, Carmen; Infortuna, Carmenrita; Chusid, Eileen; Coira, Diego; Babayev, Jacqueline; Metwaly, Rowan; Naenifard, Hesam; Aguglia, Eugenio; Battaglia, Fortunato

    2017-10-01

    Energy drinks are thought to improve certain aspects of athletic and cognitive performances. Moreover, less is understood about physiological mechanisms that might underlie these effects. The aim of this study was to examine the influence of sugar-free energy drink (SFED) ingestion on corticomotor excitability and plasticity. Fourteen college students consumed a commercially available SFED or a "dummy" drink. By using Transcranial magnetic Stimulation (TMS) we investigated resting motor threshold (RMT), motor evoked potential (MEP) amplitude and cortical silent period (CSP). Paired-pulse stimulation was used to assess short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Sensorimotor integration was investigated with the short- and long-afferent inhibition paradigms (SAI and LAI). Cortical plasticity was studied with the paired associative stimulation (PAS) paradigm. In addition, we examined the effect of SFED on simple reaction time (RT), pre-movement facilitation and post-exercise facilitation (PEF). SFED consumption decreased ICF, shortened RT, increased pre-movement facilitation and PEF of the motor evoked potentials. These results demonstrate that SFED consumption induced a shorter RT that is paralleled by changes in cortical excitability at rest, prior and after a non-fatiguing muscle contraction. These acute changes in brain function might be of relevance in understanding the mechanisms underlying the enhancement of psychomotor performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea.

    PubMed

    Drescher, M J; Drescher, D G; Khan, K M; Hatfield, J S; Ramakrishnan, N A; Abu-Hamdan, M D; Lemonnier, L A

    2006-09-29

    Pituitary adenylyl cyclase-activating polypeptide (PACAP), via its specific receptor pituitary adenylyl cyclase-activating polypeptide receptor 1 (PAC1-R), is known to have roles in neuromodulation and neuroprotection associated with glutamatergic and cholinergic neurotransmission, which, respectively, are believed to form the primary basis for afferent and efferent signaling in the organ of Corti. Previously, we identified transcripts for PACAP preprotein and multiple splice variants of its receptor, PAC1-R, in microdissected cochlear subfractions. In the present work, neural localizations of PACAP and PAC1-R within the organ of Corti and spiral ganglion were examined, defining sites of PACAP action. Immunolocalization of PACAP and PAC1-R in the organ of Corti and spiral ganglion was compared with immunolocalization of choline acetyltransferase (ChAT) and synaptophysin as efferent neuronal markers, and glutamate receptor 2/3 (GluR2/3) and neurofilament 200 as afferent neuronal markers, for each of the three cochlear turns. Brightfield microscopy giving morphological detail for individual immunolocalizations was followed by immunofluorescence detection of co-localizations. PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti. Further, evidence was obtained that PACAP is expressed in type I afferent axons leaving the spiral ganglion en route to the auditory nerve, potentially serving as a neuromodulator in axonal terminals. In contrast to the efferent localization of PACAP within the organ of Corti, PAC1-R immunoreactivity was co-localized with afferent dendritic neuronal marker GluR2/3 in nerve fibers passing beneath and lateral to the inner hair cell and in fibers at supranuclear and basal sites on outer hair cells. Given the known association of PACAP with catecholaminergic neurotransmission in sympathoadrenal function, we also re-examined the issue

  19. Wavelet Packet Analysis for Angular Data Extraction from Muscle Afferent Cuff Electrode Signals

    DTIC Science & Technology

    2001-10-25

    from rabbits. In order to estimate ankle flexion/extension angles, we recorded ENG signals from the left Tibial and Peroneal nerves, both during FES...afferent ENG. II. METHODOLOGY A. Experimental Setup Acute experiments were conducted with 2 female New Zealand rabbits. The rabbits were pre-anesthetized...fixating the knee and ankle joints in place (see [3] for more details) . For extracting the ENG signals, tripolar cuff electrodes were implanted onto the

  20. Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

    PubMed

    Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

    2014-05-01

    Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.

  1. The correlated blanching of synaptic bodies and reduction in afferent firing rates caused by transmitter-depleting agents in the frog semicircular canal

    NASA Technical Reports Server (NTRS)

    Guth, P.; Norris, C.; Fermin, C. D.; Pantoja, M.

    1993-01-01

    Synaptic bodies (SBs) associated with rings of synaptic vesicles and well-defined, pre- and post-synaptic membrane structures are indicators of maturity in most hair cell-afferent nerve junctions. The role of the SBs remains elusive despite several experiments showing that they may be involved in storage of neurotransmitter. Our results demonstrate that SBs of the adult posterior semicircular canal (SCC) cristae hair cells become less electron dense following incubation of the SCC with the transmitter-depleting drug tetrabenazine (TBZ). Objective quantification and comparison of the densities of the SBs in untreated and TBZ-treated frog SCC demonstrated that TBZ significantly decreased the electron density of SBs. This reduction in electron density was accompanied by a reduction in firing rates of afferent fibers innervating the posterior SCC. A second transmitter-depleting drug, guanethidine, previously shown to reduce the electron density of hair cell SBs, also reduced the firing rates of afferent fibers innervating the posterior SCC. In contrast, the electron density of dense granules (DG), similar in size and shape to synaptic bodies (SB) in hair cells, did not change after incubation in TBZ, thus indicating that granules and SBs are not similar in regard to their electron density. The role of SBs in synaptic transmission and the transmitter, if any, stored in the SBs remain unknown. Nonetheless, the association of the lessening of electron density with a reduction in afferent firing rate provides impetus for the further investigation of the SB's role in neurotransmission.

  2. A computational model for estimating recruitment of primary afferent fibers by intraneural stimulation in the dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Bourbeau, D. J.; Hokanson, J. A.; Rubin, J. E.; Weber, D. J.

    2011-10-01

    Primary afferent microstimulation has been proposed as a method for activating cutaneous and muscle afferent fibers to restore tactile and proprioceptive feedback after limb loss or peripheral neuropathy. Large populations of primary afferent fibers can be accessed directly by implanting microelectrode arrays in the dorsal root ganglia (DRG), which provide a compact and stable target for stimulating a diverse group of sensory fibers. To gain insight into factors affecting the number and types of primary afferents activated, we developed a computational model that simulates the recruitment of fibers in the feline L7 DRG. The model comprises two parts. The first part is a single-fiber model used to describe the current-distance relation and was based on the McIntyre-Richardson-Grill model for excitability. The second part uses the results of the singe-fiber model and published data on fiber size distributions to predict the probability of recruiting a given number of fibers as a function of stimulus intensity. The range of intensities over which exactly one fiber was recruited was approximately 0.5-5 µA (0.1-1 nC per phase); the stimulus intensity at which the probability of recruiting exactly one fiber was maximized was 2.3 µA. However, at 2.3 µA, it was also possible to recruit up to three fibers, albeit with a lower probability. Stimulation amplitudes up to 6 µA were tested with the population model, which showed that as the amplitude increased, the number of fibers recruited increased exponentially. The distribution of threshold amplitudes predicted by the model was similar to that previously reported by in vivo experimentation. Finally, the model suggested that medium diameter fibers (7.3-11.5 µm) may be recruited with much greater probability than large diameter fibers (12.8-16 µm). This model may be used to efficiently test a range of stimulation parameters and nerve morphologies to complement results from electrophysiology experiments and to aid in the

  3. Experiment K-7-31: Studies of Vestibular Primary Afferents and Eye Movements in Normal, Hypergravity and Hypogravity - Axon Cosmos Flight 2044

    NASA Technical Reports Server (NTRS)

    Correia, M. J.; Perachio, A. A.; Dickman, J. D.; Kozlovskaya, I.; Sirota, M.; Yakushin, S.; Beloozerova, I. N.

    1994-01-01

    Fourteen days of active head movements in microgravity appear to modify the gain and neural adaptation properties of the horizontal semicircular canals in the rhesus monkey. This is the first demonstration of adaptive plasticity in the sensory receptor. Reversing prisms, for example, do not modify the gain of the primary afferent response. Pulse yaw rotation, sinusoidal rotation, and sum of sinusoidal rotation testing during the first day following recovery revealed that the gain of a sample of afferents was significantly greater than the gain derived from afferent responses obtained during pre-flight and control monkey testing. There was no strong evidence of tilt sensitivity in the sample of afferents that we tested either during the pre-flight or control tests or during the first day post-flight. Two irregular afferents tested on postflight day 2 showed changes with tilt but the responses were not systematic. The spontaneous discharge did not change following flight. Mean firing rate and coefficient of variation remained constant during the post flight tests and was near the value measured during pre flight tests. The change in gain of horizontal canal afferents might be adaptive. The animals were required to look at a target for food. This required active head and eye movements. Active head movements have been shown to be hypometric and eye movements have been shown to be hypermetric during the first few days of past Cosmos flights (see introduction). It might be that the increased gain in the horizontal semicircular canals permit accurate target acquisition during hypometric head movements by driving the eyes to greater angles for smaller angles of head movement. The mechanism by which the semicircular canals recalibrate (increase their gain) is unknown. The efferent vestibular system is a logical candidate. Horizontal nystagmus during rotation about an earth vertical axis with the horizontal semicircular canals in the plane of rotation produced the same

  4. The Medial Paralemniscal Nucleus and Its Afferent Neuronal Connections in Rat

    PubMed Central

    VARGA, TAMÁS; PALKOVITS, MIKLÓS; USDIN, TED BJÖRN; DOBOLYI, ARPÁD

    2009-01-01

    Previously, we described a cell group expressing tuberoinfundibular peptide of 39 residues (TIP39) in the lateral pontomesencephalic tegmentum, and referred to it as the medial paralemniscal nucleus (MPL). To identify this nucleus further in rat, we have now characterized the MPL cytoarchitectonically on coronal, sagittal, and horizontal serial sections. Neurons in the MPL have a columnar arrangement distinct from adjacent areas. The MPL is bordered by the intermediate nucleus of the lateral lemniscus nucleus laterally, the oral pontine reticular formation medially, and the rubrospinal tract ventrally, whereas the A7 noradrenergic cell group is located immediately mediocaudal to the MPL. TIP39-immunoreactive neurons are distributed throughout the cytoarchitectonically defined MPL and constitute 75% of its neurons as assessed by double labeling of TIP39 with a fluorescent Nissl dye or NeuN. Furthermore, we investigated the neuronal inputs to the MPL by using the retrograde tracer cholera toxin B subunit. The MPL has afferent neuronal connections distinct from adjacent brain regions including major inputs from the auditory cortex, medial part of the medial geniculate body, superior colliculus, external and dorsal cortices of the inferior colliculus, periolivary area, lateral preoptic area, hypothalamic ventromedial nucleus, lateral and dorsal hypothalamic areas, subparafascicular and posterior intralaminar thalamic nuclei, periaqueductal gray, and cuneiform nucleus. In addition, injection of the anterograde tracer biotinylated dextran amine into the auditory cortex and the hypothalamic ventromedial nucleus confirmed projections from these areas to the distinct MPL. The afferent neuronal connections of the MPL suggest its involvement in auditory and reproductive functions. PMID:18770870

  5. The medial paralemniscal nucleus and its afferent neuronal connections in rat.

    PubMed

    Varga, Tamás; Palkovits, Miklós; Usdin, Ted Björn; Dobolyi, Arpád

    2008-11-10

    Previously, we described a cell group expressing tuberoinfundibular peptide of 39 residues (TIP39) in the lateral pontomesencephalic tegmentum, and referred to it as the medial paralemniscal nucleus (MPL). To identify this nucleus further in rat, we have now characterized the MPL cytoarchitectonically on coronal, sagittal, and horizontal serial sections. Neurons in the MPL have a columnar arrangement distinct from adjacent areas. The MPL is bordered by the intermediate nucleus of the lateral lemniscus nucleus laterally, the oral pontine reticular formation medially, and the rubrospinal tract ventrally, whereas the A7 noradrenergic cell group is located immediately mediocaudal to the MPL. TIP39-immunoreactive neurons are distributed throughout the cytoarchitectonically defined MPL and constitute 75% of its neurons as assessed by double labeling of TIP39 with a fluorescent Nissl dye or NeuN. Furthermore, we investigated the neuronal inputs to the MPL by using the retrograde tracer cholera toxin B subunit. The MPL has afferent neuronal connections distinct from adjacent brain regions including major inputs from the auditory cortex, medial part of the medial geniculate body, superior colliculus, external and dorsal cortices of the inferior colliculus, periolivary area, lateral preoptic area, hypothalamic ventromedial nucleus, lateral and dorsal hypothalamic areas, subparafascicular and posterior intralaminar thalamic nuclei, periaqueductal gray, and cuneiform nucleus. In addition, injection of the anterograde tracer biotinylated dextran amine into the auditory cortex and the hypothalamic ventromedial nucleus confirmed projections from these areas to the distinct MPL. The afferent neuronal connections of the MPL suggest its involvement in auditory and reproductive functions. (c) 2008 Wiley-Liss, Inc.

  6. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  7. Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset

    PubMed Central

    Schreck, Mary; Petralia, Ronald S.; Wang, Ya-Xian; Zhang, Qiuxiang

    2017-01-01

    In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons. SIGNIFICANCE STATEMENT Numerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset, a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence

  8. A geometric analysis of semicircular canals and induced activity in their peripheral afferents in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Reisine, H.; Simpson, J. I.; Henn, V.

    1988-01-01

    Experiments were carried out to determine anatomically the planes of the semicircular canals of two juvenile rhesus monkeys, using plastic casts of the semicircular canals, and the anatomical measurements were related to the directional coding of neural signals transmitted by primary afferents innervating the same simicircular canals. In the experiments, animals were prepared for monitoring the eye position by the implantation of silver-silver chloride electrodes into the bony orbit. Following the recording of semicircular canal afferent activity, the animals were sacrificed; plastic casting resin was injected into the bony canals; and, when the temporal bone was demineralized and removed, the coordinates of points spaced along the circumference of the canal casts were measured. A comparison of the sensitivity vectors determined in these experiments and the anatomical measures showed that the average difference between a sensitivity vector and its respective normal vector was 6.3 deg.

  9. Nonpainful wide-area compression inhibits experimental pain

    PubMed Central

    Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

    2016-01-01

    Abstract Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM. PMID:27152691

  10. Nonpainful wide-area compression inhibits experimental pain.

    PubMed

    Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

    2016-09-01

    Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

  11. Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

    PubMed

    DiBona, Gerald F; Jones, Susan Y

    2003-08-01

    To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus

  12. Fine structural survey of the intermediate subnucleus of the nucleus tractus solitarii and its glossopharyngeal afferent terminals.

    PubMed

    Hayakawa, Tetsu; Maeda, Seishi; Tanaka, Koichi; Seki, Makoto

    2005-10-01

    The intermediate subnucleus of the nucleus tractus solitarii (imNTS) receives somatosensory inputs from the soft palate and pharynx, and projects onto the nucleus ambiguus, thus serving as a relay nucleus for swallowing. The ultrastructure and synaptology of the rat imNTS, and its glossopharyngeal afferent terminals, have been examined with cholera toxin-conjugated horseradish peroxidase (CT-HRP) as an anterograde tracer. The imNTS contained oval or ellipsoid-shaped, small to medium-sized neurons (18.2 x 11.4 microm) with little cytoplasm, few cell organelles and an irregularly shaped nucleus. The cytoplasm often contained one or two nucleolus-like stigmoid bodies. The average number of axosomatic terminals was 1.8 per profile. About 83% of them contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), while about 17% contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). The neuropil contained small or large axodendritic terminals, and about 92% of them were Gray's type I. When CT-HRP was injected into the nodose ganglion, many labeled terminals were found in the imNTS. All anterogradely labeled terminals contacted dendrites but not somata. The labeled terminals were usually large (2.69+/-0.09 mum) and exclusively of Gray's type I. They often contacted more than two dendrites, were covered with glial processes, and formed synaptic glomeruli. A small unlabeled terminal occasionally made an asymmetric synaptic contact with a large labeled terminal. The large glossopharyngeal afferent terminals and the neurons containing stigmoid bodies characterized the imNTS neurons that received pharyngeal afferents.

  13. Physiological identification of morphologically distinct afferent classes innervating the cristae ampullares of the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Lysakowski, A.; Minor, L. B.; Fernandez, C.; Goldberg, J. M.

    1995-01-01

    1. Semicircular-canal afferents in the squirrel monkey were characterized by their resting discharge, discharge regularity, sensitivity to galvanic currents delivered to the ear (beta *), the gain (g2Hz), and phase lead (phi 2Hz) of their response to 2-Hz sinusoidal head rotations, and their antidromic conduction velocity. Discharge regularity was measured by a normalized coefficient of variation (CV*); the higher the CV*, the more irregular the discharge. g2Hz and phi 2Hz were expressed relative to angular head velocity. 2. These physiological measures were used in an attempt to discern the discharge properties of the three morphological classes of afferents innervating the crista. Presumed bouton (B) fibers were identified as slowly conducting afferents. Presumed calyx (C) fibers were recognized by their irregular discharge and low rotational gains. The remaining fibers were considered to be dimorphic (D) units. Single letters (B, C, and D) are used to emphasize that the classification is based on circumstantial evidence and may be wrong for individual fibers. Of the 125 identified fibers, 13 (10%) were B units, 36 (29%) were C units, and 76 (61%) were D units. 3. B units were regularly discharging D units ranged from regularly to irregularly discharging. C units were the most irregularly discharging afferents encountered. The mean resting discharge for the entire sample was 74 spikes/s. Resting rates were similar for regularly discharging B and D units and higher than those for irregularly discharging C and D units. 4. Except for their lower conduction velocities, the discharge properties of B units are indistinguishable from those of regularly discharging D units. Many of the discharge properties of B and D units vary with discharge regularity. There is a strong, positive relation when beta *, g2Hz, or phi 2Hz is plotted against CV*. For beta * or phi 2Hz, C units conform to the relation for B and D units. In contrast, values of g2Hz for C units are three to

  14. Fast-adapting mechanoreceptors are important for force control in precision grip but not for sensorimotor memory.

    PubMed

    Park, Susanna B; Davare, Marco; Falla, Marika; Kennedy, William R; Selim, Mona M; Wendelschafer-Crabb, Gwen; Koltzenburg, Martin

    2016-06-01

    Sensory feedback from cutaneous mechanoreceptors in the fingertips is important in effective object manipulation, allowing appropriate scaling of grip and load forces during precision grip. However, the role of mechanoreceptor subtypes in these tasks remains incompletely understood. To address this issue, psychophysical tasks that may specifically assess function of type I fast-adapting (FAI) and slowly adapting (SAI) mechanoreceptors were used with object manipulation experiments to examine the regulation of grip force control in an experimental model of graded reduction in tactile sensitivity (healthy volunteers wearing 2 layers of latex gloves). With gloves, tactile sensitivity decreased significantly from 1.9 ± 0.4 to 12.3 ± 2.2 μm in the Bumps task assessing function of FAI afferents but not in a grating orientation task assessing SAI afferents (1.6 ± 0.1 to 1.8 ± 0.2 mm). Six axis force/torque sensors measured peak grip (PGF) and load (PLF) forces generated by the fingertips during a grip-lift task. With gloves there was a significant increase of PGF (14 ± 6%), PLF (17 ± 5%), and grip and load force rates (26 ± 8%, 20 ± 8%). A variable-weight series task was used to examine sensorimotor memory. There was a 20% increase in PGF when the lift of a light object was preceded by a heavy relative to a light object. This relationship was not significantly altered when lifting with gloves, suggesting that the addition of gloves did not change sensorimotor memory effects. We conclude that FAI fibers may be important for the online force scaling but not for the buildup of a sensorimotor memory. Copyright © 2016 the American Physiological Society.

  15. Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses.

    PubMed

    Makadia, Payal A; Najjar, Sarah A; Saloman, Jami L; Adelman, Peter; Feng, Bin; Margiotta, Joseph F; Albers, Kathryn M; Davis, Brian M

    2018-06-20

    Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial-neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin-expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively. An ex vivo preparation of the colon was used for single-fiber analysis of colon sensory afferents of the pelvic nerve. Afferents were characterized using previously described criteria as mucosal, muscular, muscular-mucosal, or serosal and then tested for blue light-induced activation. Light activation of colon epithelial cells produced robust firing of action potentials, similar to that elicited by physiologic stimulation (e.g., circumferential stretch), in 50.5% of colon afferents of mice homozygous for ChR2 expression. Light-induced activity could be reduced or abolished in most fibers using a cocktail of purinergic receptor blockers suggesting ATP release by the epithelium contributed to generation of sensory neuron action potentials. Using electromyographic recording of visceromotor responses we found that light stimulation of the colon epithelium evoked behavioral responses in Vil-ChR2 mice that was similar to that seen with balloon distension of the colon. These ex vivo and in vivo data indicate that light stimulation of colon epithelial cells alone, without added mechanical or chemical stimuli, can directly activate colon afferents and elicit behavioral responses. SIGNIFICANCE STATEMENT Abdominal pain that accompanies inflammatory diseases of the bowel is particularly vexing because it can occur without obvious changes in the structure or inflammatory condition of the colon. Pain reflects abnormal sensory neuron activity that may be

  16. Presynaptic gain control by endogenous cotransmission of dopamine and GABA in the olfactory bulb.

    PubMed

    Vaaga, Christopher E; Yorgason, Jordan T; Williams, John T; Westbrook, Gary L

    2017-03-01

    In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for decorrelating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry and GABA release as measured by whole cell GABA A receptor currents. Activation of short axon cells reduced the afferent presynaptic release probability via D 2 and GABA B receptor activation, resulting in reduced spiking in both mitral and external tufted cells. Our results suggest that short axon cells influence glomerular activity not only by direct inhibition of external tufted cells but also by inhibition of afferent inputs to external tufted and mitral cells. NEW & NOTEWORTHY Sensory systems, including the olfactory system, encode information across a large dynamic range, making synaptic mechanisms of gain control critical to proper function. Here we demonstrate that a dual-transmitter interneuron in the olfactory bulb controls the gain of intraglomerular afferent input via two distinct mechanisms, presynaptic inhibition as well as inhibition of a principal neuron subtype, and thereby potently controls the synaptic gain of afferent inputs. Copyright © 2017 the American Physiological Society.

  17. Simulation studies of vestibular macular afferent-discharge patterns using a new, quasi-3-D finite volume method

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Linton, S. W.; Parnas, B. R.

    2000-01-01

    A quasi-three-dimensional finite-volume numerical simulator was developed to study passive voltage spread in vestibular macular afferents. The method, borrowed from computational fluid dynamics, discretizes events transpiring in small volumes over time. The afferent simulated had three calyces with processes. The number of processes and synapses, and direction and timing of synapse activation, were varied. Simultaneous synapse activation resulted in shortest latency, while directional activation (proximal to distal and distal to proximal) yielded most regular discharges. Color-coded visualizations showed that the simulator discretized events and demonstrated that discharge produced a distal spread of voltage from the spike initiator into the ending. The simulations indicate that directional input, morphology, and timing of synapse activation can affect discharge properties, as must also distal spread of voltage from the spike initiator. The finite volume method has generality and can be applied to more complex neurons to explore discrete synaptic effects in four dimensions.

  18. Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7 receptors in adult rats.

    PubMed

    Cabaj, Anna M; Majczyński, Henryk; Couto, Erika; Gardiner, Phillip F; Stecina, Katinka; Sławińska, Urszula; Jordan, Larry M

    2017-01-01

    Experiments on neonatal rodent spinal cord showed that serotonin (5-HT), acting via 5-HT 7 receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter- and intralimb coordination, but the importance of the 5-HT system in adult locomotion is not clear. Blockade of spinal 5-HT 7 receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5-HT neurons for production of locomotion. The direct control of coordinating interneurons by 5-HT 7 receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults. An understanding of the afferents controlled by 5-HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs. Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5-HT 7 ) receptor agonists and antagonists and 5-HT 7 receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily from in vitro studies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of serotonin (5-HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5-HT 7 receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5-HT 7 receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5-HT 7 antagonist SB269970 in adult intact rats suppressed locomotion by

  19. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report.

    PubMed

    De Cicco, Vincenzo

    2012-09-03

    A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro-afferent

  20. [The evoked activity of the lateral hypothalamus during extinction and differential inhibition].

    PubMed

    Vanetsian, G L

    1995-01-01

    Character of interaction between symmetric points of the cat's auditory cortex (A1) and the lateral hypothalamus (HL) was determined by calculating Spearman correlation coefficients between averaged summed sound-evoked activity (AEP) of the structures before, during elaboration, extinction and restoration, as well as differentiation of food-procuring conditioned reflex and in the eating full. Close mutual co-tuning between the cortex and hypothalamus characteristic for stable conditioned reflex was found to disrupted during its extinction, elaboration of differentiation and fullness eat inhibition due to entire reduction of hypothalamic AEP and disappearance of correlated with negativity of HL AEP "doubling" of the first positive wave of A1 AEP. Hyperactivity stage, expressed at the beginning of extinction and at the end of differentiation, preceded inactivation of hypothalamic afferents during elaboration of conditioned inhibition. The stage of hyperactivity, initiated by the elevated emotional state of the animal, testifies to an important role of emotional brain structures in the process of internal inhibition. The stage of HL and A1 hyperactivity initiated by emotional stress of the animal and following HL inactivation during inhibition of the conditioned response point to an important role of emotional subcortical brain structures in the mechanisms of inhibitory conditioning.

  1. Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey.

    PubMed

    Giolli, R A; Gregory, K M; Suzuki, D A; Blanks, R H; Lui, F; Betelak, K F

    2001-01-01

    Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico

  2. TRPV4 participates in pressure-induced inhibition of renin secretion by juxtaglomerular cells.

    PubMed

    Seghers, François; Yerna, Xavier; Zanou, Nadège; Devuyst, Olivier; Vennekens, Rudi; Nilius, Bernd; Gailly, Philippe

    2016-12-15

    Increase in blood pressure in the renal afferent arteriole is known to induce an increase in cytosolic calcium concentration ([Ca 2+ ] i ) of juxtaglomerular (JG) cells and to result in a decreased secretion of renin. Mechanical stimulation of As4.1 JG cells induces an increase in [Ca 2+ ] i that is inhibited by HC067047 and RN1734, two inhibitors of TRPV4, or by siRNA-mediated repression of TRPV4. Inhibition of TRPV4 impairs pressure-induced decrease in renin secretion. Compared to wild-type mice, Trpv4 -/- mice present increased resting plasma levels of renin and aldosterone and present a significantly altered pressure-renin relationship. We suggest that TRPV4 channel participates in mechanosensation at the juxtaglomerular apparatus. The renin-angiotensin system is a crucial blood pressure regulation system. It consists of a hormonal cascade where the rate-limiting enzyme is renin, which is secreted into the blood flow by renal juxtaglomerular (JG) cells in response to low pressure in the renal afferent arteriole. In contrast, an increase in blood pressure results in a decreased renin secretion. This is accompanied by a transitory increase in [Ca 2+ ] i of JG cells. The inverse relationship between [Ca 2+ ] i and renin secretion has been called the 'calcium paradox' of renin release. How increased pressure induces a [Ca 2+ ] i transient in JG cells, is however, unknown. We observed that [Ca 2+ ] i transients induced by mechanical stimuli in JG As4.1 cells were completely abolished by HC067047 and RN1734, two inhibitors of TRPV4. They were also reduced by half by siRNA-mediated repression of TRPV4 but not after repression or inhibition of TRPV2 or Piezo1 ion channels. Interestingly, the stimulation of renin secretion by the adenylate cyclase activator forskolin was totally inhibited by cyclic stretching of the cells. This effect was mimicked by stimulation with GSK1016790A and 4αPDD, two activators of TRPV4 and inhibited in the presence of HC067047. Moreover, in

  3. Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish

    PubMed Central

    Haehnel-Taguchi, Melanie; Akanyeti, Otar

    2014-01-01

    The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 μm/ms. However, spike rate did not change when the cupula was deflected below 8 μm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior. PMID:24966296

  4. Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

    PubMed

    Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

    2003-03-01

    The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

  5. [Two cases of afferent loop syndrome caused by obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop that were successfully treated by endoscopic balloon dilatation].

    PubMed

    Yasuda, Atsushi; Imamoto, Haruhiko; Furukawa, Hiroshi; Imano, Motohiro; Yasuda, Takushi; Okuno, Kiyokata

    2014-11-01

    We report 2 rare cases of afferent loop syndrome caused by obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop after total gastrectomy, which was successfully treated by endoscopic balloon dilatation of the anastomotic stenosis. Case 1: A 62-year-old woman presented with malaise and lower abdominal distension 6 months after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. She was diagnosed with afferent loop syndrome; CT imaging indicated marked dilatation of the afferent loop, with membranous obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop. Although almost complete occlusion was noted at the jejuno-jejunostomy site, the obstruction was successfully relieved by endoscopic balloon dilation using TandemTM XL Triple Lumen ERCP Cannula (Boston Scientific)®. Case 2: A 70-year-old man presented with malaise and lower abdominal distension 3 years after laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction. He was diagnosed with afferent loop syndrome; CT imaging indicated complete obstruction at the jejuno-jejunostomy site in the Roux-en-Y loop. As in case 1, the obstruction was successfully treated by endoscopic balloon dilatation of the occluded anastomosis.

  6. Spinal N-methyl-D-aspartate receptors and nociception-evoked release of primary afferent substance P.

    PubMed

    Nazarian, A; Gu, G; Gracias, N G; Wilkinson, K; Hua, X Y; Vasko, M R; Yaksh, T L

    2008-03-03

    Dorsal horn N-methyl-D-aspartate (NMDA) receptors contribute significantly to spinal nociceptive processing through an effect postsynaptic to non-primary glutamatergic axons, and perhaps presynaptic to the primary afferent terminals. The present study sought to examine the regulatory effects of NMDA receptors on primary afferent release of substance P (SP), as measured by neurokinin 1 receptor (NK1r) internalization in the spinal dorsal horn of rats. The effects of intrathecal NMDA alone or in combination with D-serine (a glycine site agonist) were initially examined on basal levels of NK1r internalization. NMDA alone or when co-administered with D-serine failed to induce NK1r internalization, whereas activation of spinal TRPV1 receptors by capsaicin resulted in a notable NK1r internalization. To determine whether NMDA receptor activation could potentiate NK1r internalization or pain behavior induced by a peripheral noxious stimulus, intrathecal NMDA was given prior to an intraplantar injection of formalin. NMDA did not alter the formalin-induced NK1r internalization nor did it enhance the formalin paw flinching behavior. To further characterize the effects of presynaptic NMDA receptors, the NMDA antagonists DL-2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 were intrathecally administered to assess their regulatory effects on formalin-induced NK1r internalization and pain behavior. AP-5 had no effect on formalin-induced NK1r internalization, whereas MK-801 produced only a modest reduction. Both antagonists, however, reduced the formalin paw flinching behavior. In subsequent in vitro experiments, perfusion of NMDA in spinal cord slice preparations did not evoke basal release of SP or calcitonin gene-related peptide (CGRP). Likewise, perfusion of NMDA did not enhance capsaicin-evoked release of the two peptides. These results suggest that presynaptic NMDA receptors in the spinal cord play little if any role on the primary afferent release of SP.

  7. Effects of adding Braun jejunojejunostomy to standard Whipple procedure on reduction of afferent loop syndrome - a randomized clinical trial.

    PubMed

    Kakaei, Farzad; Beheshtirouy, Samad; Nejatollahi, Seyed Moahammad Reza; Rashidi, Iqbal; Asvadi, Touraj; Habibzadeh, Afshin; Oliaei-Motlagh, Mohammad

    2015-12-01

    Whipple surgery (pancreaticodeudenectomy) has a high complication rate. We aimed to evaluate whether adding Braun jejunojejunostomy (side-to-side anastomosis of afferent and efferent loops distal to the gastrojejunostomy site) to a standard Whipple procedure would reduce postoperative complications. We conducted a randomized clinical trial comparing patients who underwent standard Whipple surgery (standard group) and patients who underwent standard Whipple surgery with Braun jejunojejunostomy (Braun group). Patients were followed for 1 month after the procedure and postoperative complications were recorded. Our study included 30 patients: 15 in the Braun and 15 in the standard group. In the Braun group, 4 (26.7%) patients experienced 6 complications, whereas in the standard group, 7 (46.7%) patients experienced 11 complications (p = 0.14). Complications in the Braun group were gastrointestinal bleeding and wound infection (n = 1 each) and delayed gastric emptying and pulmonary infection (n = 2 each). Complications in the standard group were death, pancreatic anastomosis leak and biliary anastomosis leak (n = 1 each); gastrointestinal bleeding (n = 2); and afferent loop syndrome and delayed gastric emptying (n = 3 each). There was no significant difference between groups in the subtypes of complications. Our results showed that adding Braun jejunojejunostomy to standard Whipple procedure was associated with lower rates of afferent loop syndrome and delayed gastric emptying. However, more studies are needed to define the role of Braun jejunojejunostomy in this regard. IRCT2014020316473N1 (www.irct.ir).

  8. Mechanisms of Selective Induction of Gastric Mucosal Eicosanoids in Response to Potentially Noxious Stimuli

    DTIC Science & Technology

    1991-04-30

    the proposed source of leukotrienes. Lidocaine (2.2 mg/kg iv bolus followed by 66 /ig/kg/min iv Infusion) was used to inhibit sensory afferents... Lidocaine significantly inhibited LTC4 generation following acid or bile, but had no effect on PGE2 synthesis after bile. Thus, the release of LTĈ...viil Effect of Inhibition of Sensory Afferent Nerves by Lidocaine on Gastric Emptying and Mucosal Eicosanoid Generation After Exposure of the

  9. Peripheral apelin-13 administration inhibits gastrointestinal motor functions in rats: The role of cholecystokinin through CCK1 receptor-mediated pathway.

    PubMed

    Bülbül, Mehmet; Sinen, Osman; Birsen, İlknur; Nimet İzgüt-Uysal, V

    2017-06-01

    Apelin is the endogenous ligand of the G protein-coupled receptor APJ. The APJ receptor is widely expressed in gastrointestinal (GI) tissues including stomach and small intestine. Apelin administration was shown to induce the release of cholecystokinin (CCK) which is a well-known alimentary hormone with its inhibitory actions on GI motor functions through CCK 1 receptors on vagal afferent fibers. We investigated whether; (i) peripherally injected apelin-13 alters GI motor functions, (ii) apelin-induced changes are mediated by APJ receptor or CCK 1 receptor and (iii) vagal afferents are involved in inhibitory effects of apelin. Solid gastric emptying (GE) and colon transit (CT) were measured, whereas duodenal phase III-like contractions were recorded in rats administered with apelin-13 (300μg/kg, ip). CCK 1 receptor antagonist lorglumide (10mg/kg, ip) or APJ receptor antagonist F13A (300μg/kg, ip) was administered 30min prior to the apelin-13 injections. Vagal afferent denervation was achieved by systemic administration of vanilloid receptor agonist capsaicin (125mg/kg, sc). Apelin-13 administration significantly (p<0.01) increased the CCK level in portal venous plasma samples. Compared with vehicle-treated rats, apelin-13 significantly delayed both GE (p<0.001) and CT (p<0.01). Pretreatment of lorglumide or F13A completely abolished the apelin-13-induced inhibitory effects on GE and CT, moreover, apelin-13 was found ineffective in rats underwent afferent denervation. F13A administration alone significantly accelerated the basal CT. Apelin-13 noticeably disturbed the duodenal fasting motor pattern by impairing phase III-like contractions while increasing the amplitudes of phase II contractions which were prevented by pretreatment of lorglumide and capsaicin. Compared with vehicle-treated rats, lorglumide and capsaicin significantly (p<0.05) reduced the apelin-13-induced increases in phase II motility index. Peripherally administered apelin-13 inhibits GI motor

  10. Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways.

    PubMed

    Dideriksen, Jakob L; Muceli, Silvia; Dosen, Strahinja; Laine, Christopher M; Farina, Dario

    2015-02-01

    Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation, but electrically evoked muscle activation is in several ways different from voluntary muscle contractions. These differences lead to challenges in the use of NMES for restoring muscle function. We investigated the use of low-current, high-frequency nerve stimulation to activate the muscle via the spinal motoneuron (MN) pool to achieve more natural activation patterns. Using a novel stimulation protocol, the H-reflex responses to individual stimuli in a train of stimulation pulses at 100 Hz were reliably estimated with surface EMG during low-level contractions. Furthermore, single motor unit recruitment by afferent stimulation was analyzed with intramuscular EMG. The results showed that substantially elevated H-reflex responses were obtained during 100-Hz stimulation with respect to a lower stimulation frequency. Furthermore, motor unit recruitment using 100-Hz stimulation was not fully synchronized, as it occurs in classic NMES, and the discharge rates differed among motor units because each unit was activated only after a specific number of stimuli. The most likely mechanism behind these observations is the temporal summation of subthreshold excitatory postsynaptic potentials from Ia fibers to the MNs. These findings and their interpretation were also verified by a realistic simulation model of afferent stimulation of a MN population. These results suggest that the proposed stimulation strategy may allow generation of considerable levels of muscle activation by motor unit recruitment that resembles the physiological conditions. Copyright © 2015 the American Physiological Society.

  11. Pulmonary arterial distension and vagal afferent nerve activity in anaesthetized dogs.

    PubMed

    Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

    2004-03-16

    Distension of the main pulmonary artery and its bifurcation are known to result in a reflex vasoconstriction and increased respiratory drive; however, these responses are observed at abnormally high distending pressures. In this study we recorded afferent activity from pulmonary arterial baroreceptors to investigate their stimulus-response characteristics and to determine whether they are influenced by physiological changes in intrathoracic pressure. In chloralose-anaesthetized dogs, a cardiopulmonary bypass was established, the pulmonary trunk and its main branches were vascularly isolated and perfused with venous blood at pulsatile pressures designed to simulate the normal pulmonary arterial pressure waveform. Afferent slips of a cervical vagus were dissected and nerve fibres identified that displayed discharge patterns with characteristics expected from pulmonary arterial baroreceptors. Recordings were obtained with (a) chest open (b) chest closed and resealed, and (c) with phasic negative intrathoracic pressures in the resealed chest. Pressure-discharge characteristics obtained in the open-chest animals indicated that the threshold pulmonary pressure (corresponding to 5% of the overall response) was 17.1 +/- 2.9 and the inflexion point of the curve was 29.2 +/- 3.3 mmHg (mean +/-S.E.M). In closed-chest animals the threshold and inflexion pressures were reduced to 12.0 +/- 1.7 and 20.7 +/- 1.8 mmHg. Application of phasic negative intrathoracic pressures further reduced the threshold and inflexion pressures to 9.5 +/- 1.2 mmHg (P < 0.05 vs. open) and 14.7 +/- 0.8 mmHg (P < 0.003 vs. open and P < 0.02 vs. atmospheric). These results indicate that under physiological conditions, with closed-chest and phasic negative intrathoracic pressure changes similar to those associated with normal breathing, activity from pulmonary baroreceptors is obtained at physiological pulmonary arterial pressures in intact animals.

  12. Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

    PubMed Central

    Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

    2017-01-01

    Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

  13. Serotonin controls initiation of locomotion and afferent modulation of coordination via 5‐HT7 receptors in adult rats

    PubMed Central

    Majczyński, Henryk; Couto, Erika; Gardiner, Phillip F.; Stecina, Katinka; Sławińska, Urszula

    2016-01-01

    Key points Experiments on neonatal rodent spinal cord showed that serotonin (5‐HT), acting via 5‐HT7 receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter‐ and intralimb coordination, but the importance of the 5‐HT system in adult locomotion is not clear.Blockade of spinal 5‐HT7 receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5‐HT neurons for production of locomotion.The direct control of coordinating interneurons by 5‐HT7 receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults.An understanding of the afferents controlled by 5‐HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs. Abstract Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5‐HT7) receptor agonists and antagonists and 5‐HT7 receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily from in vitro studies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of serotonin (5‐HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5‐HT7 receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5‐HT7 receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5‐HT7 antagonist SB269970 in adult

  14. Stricture of the afferent isoperistaltic tubular segment: a late and rare cause of bilateral dilation of the upper urinary tract after ileal bladder substitution.

    PubMed

    Kiss, Bernhard; Schöndorf, Daniel; Studer, Urs E; Roth, Beat

    2013-08-01

    To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. C-tactile afferent stimulating touch carries a positive affective value.

    PubMed

    Pawling, Ralph; Cannon, Peter R; McGlone, Francis P; Walker, Susannah C

    2017-01-01

    The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli

  16. Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans.

    PubMed

    Cui, Jian; McQuillan, Patrick M; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

    2012-08-15

    We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

  17. Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

    PubMed

    Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

    2015-10-01

    Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

  18. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    PubMed Central

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  19. Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers.

    PubMed

    Friberg, D; Gazelius, B; Hökfelt, T; Nordlander, B

    1997-07-23

    Habitual snoring precedes obstructive sleep apnea (OSA), but the pathophysiological mechanisms behind progression are still unclear. The patency of upper airways depends on a reflexogen mechanism reacting on negative intrapharyngeal pressure at inspiration, probably mediated by mucosal receptors, i.e., via afferent nerve endings. Such nerves contain a specific nerve protein, protein-gene product 9.5 (PGP 9.5) and in some cases substance P (SP) and calcitonin gene-related (CGRP). Biopsies of the soft palatial mucosa were obtained from non-smoking men ten OSA patients, 11 habitual snorers and 11 non-snoring controls. The specimens were immunohistochemically analyzed for PGP 9.5, SP and CGRP. As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium. Using double staining methodology, it could be shown that SP- and CGRP-like immunoreactivities (LIs) often coexisted in these fibres, as did CGRP- and PGP 9.5-LIs. The increased density in sensory nerve terminals are interpreted to indicate an afferent nerve lesion. Our results support the hypothesis of a progressive neurogenic lesion as a contributory factor to the collapse of upper airways during sleep in OSA patients.

  20. Gastric Electrical Stimulation Decreases Gastric Distension-Induced Central Nociception Response through Direct Action on Primary Afferents

    PubMed Central

    Ouelaa, Wassila; Ghouzali, Ibtissem; Langlois, Ludovic; Fetissov, Serguei; Déchelotte, Pierre; Ducrotté, Philippe; Leroi, Anne Marie; Gourcerol, Guillaume

    2012-01-01

    Background & Aims Gastric electrical stimulation (GES) is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. Methods Gastric pain was induced by performing gastric distension (GD) in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation), while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. Results GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9–T10), the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. Conclusions GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception. PMID:23284611

  1. Cutaneous afferents mediating the cutaneous silent period in the upper limbs: evidences for a role of low-threshold sensory fibres.

    PubMed

    Serrao, M; Parisi, L; Pierelli, F; Rossi, P

    2001-11-01

    To evaluate the contribution of the low-threshold afferents to the production of the cutaneous silent period (CSP) in the upper limbs. The CSP was studied in 10 healthy adults and 4 patients with Friedreich's ataxia. The following neurophysiological aspects were studied: (a) relationship between sensory threshold (ST), sensory action potential (SAP) amplitude and CSP parameters; (b) habituation and recovery cycle of the CSP at different stimulus intensities (2xST and 8xST); (c) pattern of responses in distal and proximal muscles at different stimulus intensities (2xST and 8xST). (a) The CSP occurred at low intensities (1xST and 2xST) and increased abruptly between 3.5xST and 4xST (corresponding to the pain threshold). The SAP amplitude was saturated before CSP saturation. In the patients with Friedreich's ataxia, the CSP appeared only at higher stimulus intensities (6xST-8xST). (b) The CSP evoked at 2xST showed a fast habituation and slow recovery cycle whereas the opposite behaviour was found at 8xST. (c) Low-threshold stimuli induced an inhibitory response restricted to the distal muscles. High-intensity stimulation produced an electromyographic suppression, significantly increasing from proximal to distal muscles. Our findings support the notion that low-threshold afferents participate in the production of the CSP in the upper limbs. The different afferents may activate different central neural networks with separate functional significance.

  2. Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice.

    PubMed

    Zhang, Suping; Huang, Qian; Wang, Qiaoling; Wang, Qin; Cao, Xiaoyun; Zhao, Liang; Xu, Nan; Zhuge, Zhengbing; Mao, Jianhua; Fu, Xiaodong; Liu, Ruisheng; Wilcox, Christopher S; Patzak, Andreas; Li, Lingli; Lai, En Yin

    2018-05-30

    Canonical Wnt signaling is involved in oxidative stress, vasculopathy and diabetes mellitus but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1). Streptozotocin-induced diabetes or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg-1·day-1) to block Wnt signaling for 4 weeks. ET-1 contractions were measured by changes of afferent arteriolar diameter. Arteriolar H2O2, O2 -, protein expression and enzymatic activity were assessed using sensitive fluorescence probes, immunoblotting and colorimetric assay separately. Compared to control, diabetic mouse afferent arteriole had increased O2- (+ 84%) and H2O2 (+ 91%) and enhanced responses to ET-1 at 10-8 mol·l-1 (-72±4% of versus -43±4%, P< 0.05) accompanied by reduced protein expressions and activities for catalase and superoxide dismutase 2 (SOD2). Arteriolar O2 - was increased further by ET-1 and contractions to ET-1 reduced by PEG-SOD in both groups whereas H2O2 unchanged by ET-1 and contractions were reduced by PEG-catalase selectively in diabetic mice. The Wnt signaling protein β-catenin was upregulated (3.3-fold decrease in p-β-catenin/β-catenin) while the glycogen synthase kinase-3β (GSK-3β) was downregulated (2.6-fold increase in p-GSK-3β/ GSK-3β) in preglomerular vessels of diabetic mice. Sulindac normalized the Wnt signaling proteins, arteriolar O2 -, H2O2 and ET-1 contractions while doubling microvascular catalase and SOD2 expression in diabetic mice. Increased ROS, notably H2O2 contributes to enhanced afferent arteriolar responses to ET-1 in diabetes, which is closely associated with Wnt signaling. Antioxidant pharmacological strategies targeting Wnt signaling may improve vascular function in diabetic nephropathy. © 2018 The Author(s). Published by S. Karger AG, Basel.

  3. Synaptic GluN2A and GluN2B Containing NMDA Receptors within the Superficial Dorsal Horn Activated following Primary Afferent Stimulation

    PubMed Central

    MacDermott, Amy B.

    2014-01-01

    NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers, typically composed of two GluN1 and two of four GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits in pain transmission yet functional synaptic localization of these receptor subtypes in the dorsal horn has not been fully resolved. In this study, we have investigated the composition of synaptic NMDA receptors expressed in monosynaptic and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in rats. We focused on substance P receptor-expressing (NK1R+) projection neurons, critical for expression of hyperalgesia and allodynia. EAB-318 and (R)-CPP, GluN2A/B antagonists, blocked both monosynaptic and polysynaptic NMDA EPSCs initiated by primary afferent activation by ∼90%. Physiological measurements exploiting the voltage dependence of monosynaptic EPSCs similarly indicated dominant expression of GluN2A/B types of synaptic NMDA receptors. In addition, at synapses between C fibers and NK1R+ neurons, NMDA receptor activation initiated a secondary, depolarizing current. Ifenprodil, a GluN2B antagonist, caused modest suppression of monosynaptic NMDA EPSC amplitudes, but had a widely variable, sometimes powerful, effect on polysynaptic responses following primary afferent stimulation when inhibitory inputs were blocked to mimic neuropathic pain. We conclude that GluN2B subunits are moderately expressed at primary afferent synapses on lamina I NK1R+ neurons, but play more important roles for polysynaptic NMDA EPSCs driven by primary afferents following disinhibition, supporting the view that the analgesic effect of the GluN2B antagonist on neuropathic pain is at least in part, within the spinal cord. PMID:25122884

  4. Afferent connections of nervus facialis and nervus glossopharyngeus in the pigeon (Columba livia) and their role in feeding behavior.

    PubMed

    Dubbeldam, J L

    1984-01-01

    The afferent connections of the facial nerve and glossopharyngeal nerve in the pigeon have been studied with the Fink-Heimer I method after ganglion lesions. The nucleus ventrolateralis anterior of the solitary complex and an indistinct cell group S VII medial to the nucleus interpolaris of the descending trigeminal tract are the terminal fields for facial afferents. The n. ventrolateralis anterior also receives an important projection from the distal glossopharyngeal ganglion. Other projection areas of this ganglion are the n. presulcalis , n. centralis anterior, n. intermedius anterior and the parasolitary nucleus. Both ganglia have only ipsilateral projections. A lesion in the jugular ganglion complex causes degeneration throughout the ipsilateral solitary complex, in the contralateral n. commissuralis and n. centralis posterior and in the n. cuneatus externus. The lack of a substantial contribution to the trigeminal system is ascribed to the absence of mechanoreceptors in the tongue. The implications for the organization of neuronal pathways related to the feeding behavior are discussed.

  5. Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex.

    PubMed

    López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M

    2015-01-01

    Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals' avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations.

  6. Different forms of decision-making involve changes in the synaptic strength of the thalamic, hippocampal, and amygdalar afferents to the medial prefrontal cortex

    PubMed Central

    López-Ramos, Juan Carlos; Guerra-Narbona, Rafael; Delgado-García, José M.

    2015-01-01

    Decision-making and other cognitive processes are assumed to take place in the prefrontal cortex. In particular, the medial prefrontal cortex (mPFC) is identified in rodents by its dense connectivity with the mediodorsal (MD) thalamus, and because of its inputs from other sites, such as hippocampus and amygdala (Amyg). The aim of this study was to find a putative relationship between the behavior of mice during the performance of decision-making tasks that involve penalties as a consequence of induced actions, and the strength of field postsynaptic potentials (fPSPs) evoked in the prefrontal cortex from its thalamic, hippocampal, and amygdalar afferents. Mice were chronically implanted with stimulating electrodes in the MD thalamus, the hippocampal CA1 area, or the basolateral amygdala (BLA), and with recording electrodes in the prelimbic/infralimbic area of the prefrontal cortex. Additional stimulating electrodes aimed at evoking negative reinforcements were implanted on the trigeminal nerve. FPSPs evoked at the mPFC from the three selected projecting areas during the food/shock decision-making task decreased in amplitude with shock intensity and animals’ avoidance of the reward. FPSPs collected during the operant task also decreased in amplitude (but that evoked by amygdalar stimulation) when lever presses were associated with a trigeminal shock. Results showed a general decrease in the strength of these potentials when animals inhibited their natural or learned appetitive behaviors, suggesting an inhibition of the prefrontal cortex in these conflicting situations. PMID:25688195

  7. Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar nuclei

    PubMed Central

    Pugh, Jason R.; Raman, Indira M.

    2009-01-01

    Many cerebellar neurons fire spontaneously, generating 10–100 action potentials per second even without synaptic input. This high basal activity correlates with information-coding mechanisms that differ from those of cells that are quiescent until excited synaptically. For example, in the deep cerebellar nuclei, Hebbian patterns of coincident synaptic excitation and postsynaptic firing fail to induce long-term increases in the strength of excitatory inputs. Instead, excitatory synaptic currents are potentiated by combinations of inhibition and excitation that resemble the activity of Purkinje and mossy fiber afferents that is predicted to occur during cerebellar associative learning tasks. Such results indicate that circuits with intrinsically active neurons have rules for information transfer and storage that distinguish them from other brain regions. PMID:19178955

  8. Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.

    PubMed

    Lemieux, Maxime; Chauvette, Sylvain; Timofeev, Igor

    2015-02-01

    During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state. Copyright © 2015 the American Physiological Society.

  9. Cognitive demand does not influence the responsiveness of homonymous Ia afferents pathway during postural dual task in young and elderly adults.

    PubMed

    Baudry, Stéphane; Gaillard, Vinciane

    2014-02-01

    This study was designed to investigate the influence of a cognitive task on the responsiveness of the homonymous Ia afferents pathway during upright standing in young and elderly adults. Twelve young and twelve elderly adults stood upright on a foam surface positioned over a force platform, and performed a colour-naming test (cognitive task) with two cognitive loads: congruent and incongruent colour conditions. The rate of correct response in naming colour (accuracy) and associated reaction time (RT) were recorded for the cognitive task. The excursion of the centre of pressure and surface electromyogramme (EMG) of leg muscles were measured. Modulation in the efficacy of homonymous Ia afferents to discharge spinal motor neurones was assessed by means of the Hoffmann (H) reflex method. The accuracy and RT were similar in the congruent condition between young and elderly adults (p > 0.05), and increased for both age groups in the incongruent condition, but more so for elderly adults (p = 0.014). In contrast, the H reflex amplitude did not change with the cognitive load. The excursions of the centre of pressure in the sagittal plane and muscle EMG did not vary with colour conditions in both groups (p > 0.05). This study indicates a lack of modulation in the efficacy of group Ia afferent to activate soleus motor neurones with the cognitive demand of a concurrent task during upright standing in young and elderly adults.

  10. Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity.

    PubMed

    Kopp, Ulla C; Jones, Susan Y; DiBona, Gerald F

    2008-12-01

    Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.

  11. Silent Damage of Noise on Cochlear Afferent Innervation in Guinea Pigs and the Impact on Temporal Processing

    PubMed Central

    He, Tingting; Aiken, Steve; Bance, Manohar; Yin, Shankai; Wang, Jian

    2012-01-01

    Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs “silently” in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period. PMID:23185359

  12. Monosynaptic convergence of chorda tympani and glossopharyngeal afferents onto ascending relay neurons in the nucleus of the solitary tract: A high-resolution confocal and correlative electron microscopy approach

    PubMed Central

    Corson, James A.; Erisir, Alev

    2014-01-01

    While physiological studies suggested convergence of chorda tympani and glossopharyngeal afferent axons onto single neurons of the rostral nucleus of the solitary tract (rNTS), anatomical evidence has been elusive. The current study uses high-magnification confocal microscopy to identify putative synaptic contacts from afferent fibers of the two nerves onto individual projection neurons. Imaged tissue is re-visualized with electron microscopy, confirming that overlapping fluorescent signals in confocal z-stacks accurately identify appositions between labeled terminal and dendrite pairs. Monte Carlo modeling reveals that the probability of overlapping fluorophores is stochastically unrelated to the density of afferent label suggesting that convergent innervation in the rNTS is selective rather than opportunistic. Putative synaptic contacts from each nerve are often compartmentalized onto dendrite segments of convergently innervated neurons. These results have important implications for orosensory processing in the rNTS, and the techniques presented here have applications in investigations of neural microcircuitry with an emphasis on innervation patterning. PMID:23640852

  13. A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro.

    PubMed

    Badie-Mahdavi, H; Worsley, M A; Ackley, M A; Asghar, A U; Slack, J R; King, A E

    2001-08-01

    Expression of the inducible transcription factor Fos in the spinal dorsal horn in vivo is associated with nociceptive afferent activation, but the underlying stimulation-transcription pathway is less clear. This in vitro spinal cord study concerns the role of protein kinase A and C second messengers in substance P receptor (NK1R)-mediated or nociceptive afferent-evoked neuronal excitation and Fos expression. Nociceptive afferent (dorsal root) stimulation of isolated spinal cords (10-14 day old rats) evoked a 'prolonged' excitatory polysynaptic potential (DR-EPSP) that was attenuated (P < 0.05) by: the protein kinase A inhibitor, Rp-cAMP; the protein kinase C inhibitor, bisindolymaleimide I; and the selective NK1R antagonist, GR82334. Neuronal excitations induced by the NK1R agonist [Sar9,Met(O2)11]-SP were attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. Effects of the protein kinase A and C inhibitors on the DR-EPSP or the [Sar9,Met(O2)11]-SP-induced depolarization were nonadditive, suggesting convergence of these intracellular signalling pathways onto a common final target. Nociceptor afferent-induced Fos, detected by immunohistochemistry in superficial and deep dorsal horn laminae, was attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. In spinal cords pretreated with TTX to eliminate indirect neuronal activation, [Sar9,Met(O2)11]-SP (1-20 microM) elicited a dose-related expression of Fos that was reduced by Rp-cAMP, bisindolymaleimide I and GR82334. The effects of these inhibitors were most pronounced in the deep laminae. These data support a causal relationship between protein kinase A- or C-dependent signal transduction, nociceptive afferent- or NK1R-induced neuronal excitation and Fos expression in dorsal horn. Implications for short- versus long-term modulation of nociceptive circuitry are discussed.

  14. Muscle afferent potential (`A-wave') in the surface electromyogram of a phasic stretch reflex in normal humans

    PubMed Central

    Clarke, Alex. M.; Michie, Patricia T.; Glue, Leonard C. T.

    1972-01-01

    The experiments reported in this paper tested the hypothesis that the afferent potential elicited by a tendon tap in an isometrically recorded phasic stretch reflex can be detected in the surface EMG of normal humans when appropriate techniques are used. These techniques involved (1) training the subjects to relax mentally and physically so that the EMG was silent before and immediately after the diphasic MAP which reflects a highly synchronous discharge of afferent impulses from low threshold muscle stretch receptors after a tendon tap, and (2) using a data retrieval computer to summate stimulus-locked potentials in the EMG over a series of 16 samples using taps of uniform peak force and duration on the Achilles tendon to elicit the tendon jerk in the calf muscles. A discrete, diphasic potential (`A-wave') was recorded from EMG electrodes placed on the surface of the skin over the medial gastrocnemius muscle. The `A-wave' afferent potential had the opposite polarity to the corresponding efferent MAP. Under control conditions of relaxation the `A-wave' had a latency after the onset of the tap of 2 msec, the peak to peak amplitude was of the order of 5 μV and the duration was in the range of 6 to 10 msec. Further experiments were conducted to show that the `A-wave' (1) was not an artefact of the instrumentation used, (2) had a threshold at low intensities of stimulation, and (3) could be reliably augmented by using a Jendrassik manoeuvre compared with the potential observed during control (relaxation) conditions. The results support the conclusion that the `A-wave' emanates from the pool of muscle spindles which discharges impulses along group Ia nerve fibres in response to the phasic stretch stimulus because the primary ending of the spindles is known to initiate the stretch reflex and the spindles can be sensitized by fusimotor impulses so that their threshold is lowered as a result of a Jendrassik manoeuvre. The finding has important implications for the

  15. Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch

    PubMed Central

    Morales-Lázaro, Sara L.; Llorente, Itzel; Sierra-Ramírez, Félix; López-Romero, Ana E.; Ortíz-Rentería, Miguel; Serrano-Flores, Barbara; Simon, Sidney A.; Islas, León D.; Rosenbaum, Tamara

    2016-01-01

    The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation. PMID:27721373

  16. Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

    PubMed

    Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

    2015-12-01

    The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

  17. Ionic liquid and aqueous two-phase extraction based on salting-out coupled with high-performance liquid chromatography for the determination of seven rare ginsenosides in Xue-Sai-Tong injection.

    PubMed

    Li, Lan-Jie; Jin, Yong-Ri; Wang, Xiao-Zhong; Liu, Ying; Wu, Qian; Shi, Xiao-Lei; Li, Xu-Wen

    2015-09-01

    A method of ionic liquid salt aqueous two-phase extraction coupled with high-performance liquid chromatography has been developed for the analysis of seven rare ginsenosides including Rg6 , F4 , 20(S)-Rg3 , 20(R)-Rg3 , Rk3 , Rk1 , and Rg5 in Xue-Sai-Tong injection. The injection was mixed with ionic liquid 1-butyl-3-methylimidazolium bromide aqueous solution, and a mixture was obtained. With the addition of sodium dodecyl sulfate and dipotassium phosphate into the mixture, the aqueous two-phase mixture was formed after ultrasonic treatment and centrifuged. Rare ginsenosides were extracted into the upper phase. To obtain a high extraction factors, various influences were considered systematically, such as the volume of ionic liquid, the category and amount of salts, the amount of sodium dodecyl sulfate, the pH value of system, and the time of ultrasonic treatment. Under the optimal condition, rare ginsenosides in Xue-Sai-Tong injection were enriched and detected, the recoveries of seven rare ginsenosides ranged from 90.05 to 112.55%, while relative standard deviations were lower than 2.50%. The developed method was reliable, rapid and sensitive for the determination of seven rare ginsenosides in the injections. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

    PubMed

    Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

    2017-08-15

    The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6)

    PubMed Central

    2012-01-01

    Background Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6) levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation. Results Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment. Conclusions Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses contribute to migraine

  20. Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn

    PubMed Central

    2011-01-01

    Background Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). Results Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ± 4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. Conclusions The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways. PMID:22152428

  1. Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

    PubMed Central

    Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

    2013-01-01

    Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

  2. Spinal cord stimulation paresthesia and activity of primary afferents.

    PubMed

    North, Richard B; Streelman, Karen; Rowland, Lance; Foreman, P Jay

    2012-10-01

    A patient with failed back surgery syndrome reported paresthesia in his hands and arms during a spinal cord stimulation (SCS) screening trial with a low thoracic electrode. The patient's severe thoracic stenosis necessitated general anesthesia for simultaneous decompressive laminectomy and SCS implantation for chronic use. Use of general anesthesia gave the authors the opportunity to characterize the patient's unusual distribution of paresthesia. During SCS implantation, they recorded SCS-evoked antidromic potentials at physiologically relevant amplitudes in the legs to guide electrode placement and in the arms as controls. Stimulation of the dorsal columns at T-8 evoked potentials in the legs (common peroneal nerves) and at similar thresholds, consistent with the sensation of paresthesia in the arms, in the right ulnar nerve. The authors' electrophysiological observations support observations by neuroanatomical specialists that primary afferents can descend several (in this case, at least 8) vertebral segments in the spinal cord before synapsing or ascending. This report thus confirms a physiological basis for unusual paresthesia distribution associated with thoracic SCS.

  3. State-space decoding of primary afferent neuron firing rates

    NASA Astrophysics Data System (ADS)

    Wagenaar, J. B.; Ventura, V.; Weber, D. J.

    2011-02-01

    Kinematic state feedback is important for neuroprostheses to generate stable and adaptive movements of an extremity. State information, represented in the firing rates of populations of primary afferent (PA) neurons, can be recorded at the level of the dorsal root ganglia (DRG). Previous work in cats showed the feasibility of using DRG recordings to predict the kinematic state of the hind limb using reverse regression. Although accurate decoding results were attained, reverse regression does not make efficient use of the information embedded in the firing rates of the neural population. In this paper, we present decoding results based on state-space modeling, and show that it is a more principled and more efficient method for decoding the firing rates in an ensemble of PA neurons. In particular, we show that we can extract confounded information from neurons that respond to multiple kinematic parameters, and that including velocity components in the firing rate models significantly increases the accuracy of the decoded trajectory. We show that, on average, state-space decoding is twice as efficient as reverse regression for decoding joint and endpoint kinematics.

  4. Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal afferents mediating the Bezold-Jarisch reflex

    NASA Technical Reports Server (NTRS)

    Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

    2000-01-01

    The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) desensitize upon repeated exposure to selective agonists. BJR-mediated falls in heart rate, diastolic arterial blood pressure and cardiac output elicited by the 5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT (100 microg/kg, i.v.), progressively diminished upon repeated injection in conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly reduced in rats which had received the above injections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S-nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the injections of the 5-HT(3) receptor agonists. These findings suggest that tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5-HT(3) receptors on cardiopulmonary afferents rather than the impairment of the central or peripheral processing of the BJR.

  5. A food-predictive cue attributed with incentive salience engages subcortical afferents and efferents of the paraventricular nucleus of the thalamus

    PubMed Central

    Haight, Joshua L.; Fuller, Zachary L.; Fraser, Kurt M.; Flagel, Shelly B.

    2016-01-01

    The paraventricular nucleus of the thalamus (PVT) has been implicated in behavioral responses to reward-associated cues. However, the precise role of the PVT in these behaviors has been difficult to ascertain since Pavlovian-conditioned cues can act as both predictive and incentive stimuli. The “sign-tracker/goal-tracker” animal model has allowed us to further elucidate the role of the PVT in cue-motivated behaviors, identifying this structure as a critical component of the neural circuitry underlying individual variation in the propensity to attribute incentive salience to reward cues. The current study assessed differences in the engagement of specific PVT afferents and efferents in response to presentation of a food-cue that had been attributed with only predictive value or with both predictive and incentive value. The retrograde tracer fluorogold (FG) was injected into the PVT or the nucleus accumbens (NAc), and cue-induced c-Fos in FG-labeled cells was quantified. Presentation of a predictive stimulus that had been attributed with incentive value elicited c-Fos in PVT afferents from the lateral hypothalamus, medial amygdala (MeA), and the prelimbic cortex (PrL), as well as posterior PVT efferents to the NAc. PVT afferents from the PrL also showed elevated c-Fos levels following presentation of a predictive stimulus alone. Thus, presentation of an incentive stimulus results in engagement of subcortical brain regions; supporting a role for the hypothalamic-thalamic-striatal axis, as well as the MeA, in mediating responses to incentive stimuli; whereas activity in the PrL to PVT pathway appears to play a role in processing the predictive qualities of reward-paired stimuli. PMID:27793779

  6. Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

    PubMed

    Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

    2013-09-03

    Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

  7. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    NASA Technical Reports Server (NTRS)

    Cochran, S. L.

    1995-01-01

    The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

  8. Capsaicin-induced glutamate release is implicated in nociceptive processing through activation of ionotropic glutamate receptors and group I metabotropic glutamate receptor in primary afferent fibers.

    PubMed

    Jin, You-Hong; Yamaki, Fumiko; Takemura, Motohide; Koike, Yuichi; Furuyama, Akira; Yonehara, Norifumi

    2009-02-01

    Glutamate (Glu) is the major excitatory neurotransmitter in the central nervous system. The role of peripheral Glu and Glu receptors (GluRs) in nociceptive transmission is, however, still unclear. In the present study, we examined Glu levels released in the subcutaneous perfusate of the rat hind instep using a microdialysis catheter and the thermal withdrawal latency using the Plantar Test following injection of drugs associated with GluRs with/without capsaicin into the hindpaw. The injection of capsaicin into the rat hind instep caused an increase of Glu level in the s.c. perfusate. Capsaicin also significantly decreased withdrawal latency to irradiation. These effects of capsaicin were inhibited by pretreatment with capsazepine, a transient receptor potential vanilloid receptor 1 (TRPV1) competitive antagonist. Capsaicin-induced Glu release was also suppressed by combination with each antagonist of ionotropic GluRs (iGluRs: NMDA/AMPA receptors) and group I metabotropic GluR (mGluR), but not group II and group III mGluRs. Furthermore, these GluRs antagonists showed remarkable inhibition against capsaicin-induced thermal hyperalgesia. These results suggest that Glu is released from the peripheral endings of small-diameter afferent fibers by noxious stimulation and then activates peripheral iGluRs and group I mGluR in development and/or maintenance of nociception. Furthermore, the activation of peripheral NMDA/AMPA receptors and group I mGluR may be important in mechanisms whereby capsaicin evokes nociceptive responses.

  9. Pharmacology of Vagal Afferent Influences on Disordered Breathing During Sleep

    PubMed Central

    Carley, David W; Radulovacki, Miodrag

    2008-01-01

    Sleep related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of ∼2% of women and ∼4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved. PMID:18694851

  10. The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

    PubMed

    Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

    2017-08-10

    Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Evolution of a new sense for wind in flying phasmids? Afferents and interneurons

    NASA Astrophysics Data System (ADS)

    Hustert, Reinhold; Klug, Rebecca

    2009-12-01

    The evolution of winged stick insects (phasmids) from secondarily wingless ancestors was proposed in recent studies. We explored the cuticle of flying phasmids for wind sensors that could be involved in their flight control, comparable to those known for locusts. Surprisingly, wind-sensitive hairs (wsH) occur on the palps of mouthparts and on the antennae of the winged phasmid Sipyloidea sipylus which can fly in tethered position only when air currents blow over the mouthparts. The present study describes the morphology and major functional properties of these “new” wsH with soft and bulging hair bases which are different from the beaker-like hair bases of the wsH on the cerci of phasmids and the wsH described in other insects. The most sensitive wsH of antennae and palps respond with phasic-tonic afferents to air currents exceeding 0.2 ms-1. The fields of wsH on one side of the animal respond mainly to ventral, lateral, and frontal wind on the ipsilateral side of the head. Afferent inputs from the wsH converge but also diverge to a group of specific interneurons at their branches in the suboesophageal ganglion and can send their integrated input from wsH fields of the palps and antennae to the thoracic central nervous system. Response types of individual wsH-interneurons are either phasic or phasic-tonic to air puffs or constant air currents and also, the receptive fields of individual interneurons differ. We conclude that the “new” wsH system and its interneurons mainly serve to maintain flight activity in airborne phasmids and also, the “new” wsH must have emerged together with the integrating interneurons during the evolution from wingless to the recent winged forms of phasmids.

  12. The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension.

    PubMed

    Shafton, Anthony D; Furness, John B; Ferens, Dorota; Bogeski, Goce; Koh, Shir Lin; Lean, Nicholas P; Kitchener, Peter D

    2006-07-01

    Noxious stimuli that are applied to different somatic sites interact; often one stimulus diminishes the sensation elicited from another site. By contrast, inhibitory interactions between visceral stimuli are not well documented. We investigated the interaction between the effects of noxious distension of the colorectum and noxious stimuli applied to the jejunum, in the rat. Colorectal distension elicited a visceromotor reflex, which was quantified using electromyographic (EMG) recordings from the external oblique muscle of the upper abdomen. The same motor units were activated when a strong pinch was applied to the flank skin. Distension of the jejunum did not provoke an EMG response at this site, but when it was applied during colorectal distension it blocked the EMG response. Jejunal distension also inhibited the response to noxious skin pinch. The inhibition of the visceromotor response to colorectal distension was prevented by local application of tetrodotoxin to the jejunum, and was markedly reduced when nicardipine was infused into the local jejunal circulation. Chronic sub-diaphragmatic vagotomy had no effect on the colorectal distension-induced EMG activity or its inhibition by jejunal distension. The nicotinic antagonist hexamethonium suppressed phasic contractile activity in the jejunum, had only a small effect on the inhibition of visceromotor response by jejunal distension. It is concluded that signals that arise from skin pinch and colorectal distension converge in the central nervous system with pathways that are activated by jejunal spinal afferents; the jejunal signals strongly inhibit the abdominal motor activity evoked by noxious stimuli.

  13. Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

    PubMed Central

    Taylor, Bradley K.; Fu, Weisi; Kuphal, Karen E.; Stiller, Carl-Olav; Winter, Michelle K.; Chen, Wenling; Corder, Gregory F.; Urban, Janice H.; McCarson, Kenneth E.; Marvizon, Juan Carlos

    2014-01-01

    Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu31, Pro34]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu31, Pro34]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu31, Pro34]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [35S]GTPγS binding simulated by [Leu31, Pro34]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception. PMID:24184981

  14. A food-predictive cue attributed with incentive salience engages subcortical afferents and efferents of the paraventricular nucleus of the thalamus.

    PubMed

    Haight, Joshua L; Fuller, Zachary L; Fraser, Kurt M; Flagel, Shelly B

    2017-01-06

    The paraventricular nucleus of the thalamus (PVT) has been implicated in behavioral responses to reward-associated cues. However, the precise role of the PVT in these behaviors has been difficult to ascertain since Pavlovian-conditioned cues can act as both predictive and incentive stimuli. The "sign-tracker/goal-tracker" rat model has allowed us to further elucidate the role of the PVT in cue-motivated behaviors, identifying this structure as a critical component of the neural circuitry underlying individual variation in the propensity to attribute incentive salience to reward cues. The current study assessed differences in the engagement of specific PVT afferents and efferents in response to presentation of a food-cue that had been attributed with only predictive value or with both predictive and incentive value. The retrograde tracer fluorogold (FG) was injected into the PVT or the nucleus accumbens (NAc) of rats, and cue-induced c-Fos in FG-labeled cells was quantified. Presentation of a predictive stimulus that had been attributed with incentive value elicited c-Fos in PVT afferents from the lateral hypothalamus, medial amygdala (MeA), and the prelimbic cortex (PrL), as well as posterior PVT efferents to the NAc. PVT afferents from the PrL also showed elevated c-Fos levels following presentation of a predictive stimulus alone. Thus, presentation of an incentive stimulus results in engagement of subcortical brain regions; supporting a role for the hypothalamic-thalamic-striatal axis, as well as the MeA, in mediating responses to incentive stimuli; whereas activity in the PrL to PVT pathway appears to play a role in processing the predictive qualities of reward-paired stimuli. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

    PubMed Central

    Kopp, Ulla C.; Jones, Susan Y.; DiBona, Gerald F.

    2008-01-01

    Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, −60 ± 4 vs. −77 ± 6%. Maximum gain, −4.22 ± 0.45 vs. −6.04 ± 0.90% ΔERSNA/mmHg, and the maximum value of instantaneous gain, −4.19 ± 0.45 vs. −6.04 ± 0.81% ΔERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 ± 0.2 vs. 6.1 ± 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 ± 4,900 vs. 20,900 ± 3,410%·s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet. PMID:18945951

  16. Lesioning of TRPV1 Expressing Primary Afferent Neurons Prevents PAR-2 Induced Motility, but Not Mechanical Hypersensitivity in the Rat Colon

    PubMed Central

    Suckow, Shelby K.; Anderson, Ethan M.; Caudle, Robert M.

    2011-01-01

    Background Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Methods Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. TRPV1 expressing neurons were selectively lesioned with resiniferatoxin. Key Results In vitro the PAR-2 agonists trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. Conclusions and Inferences Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome. PMID:22168801

  17. Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.

    PubMed

    Suckow, S K; Anderson, E M; Caudle, R M

    2012-03-01

    Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. Transient receptor potential vanilloid 1 expressing neurons were selectively lesioned with resiniferatoxin. In vitro, the PAR-2 agonists, trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome. © 2011 Blackwell Publishing Ltd.

  18. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

    PubMed Central

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity. PMID:26485650

  19. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

    PubMed

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

  20. Preliminary Monitoring of Soil gas Radon in Potentially Active Faults, San Sai District, Chiang Mai Province, Thailand

    NASA Astrophysics Data System (ADS)

    Pondthai, P.; Udphuay, S.

    2013-05-01

    The magnitude of 5.1 Mw earthquake occurred in San Sai District, Chiang Mai Province, Thailand in December 2006 was considered an uncommon event due to the fact that there was no statistical record of such significant earthquake in the area. Therefore the earthquake might have been associated with a potentially active fault zone within the area. The objective of this study is to measure soil gas radon across this unknown fault zone within the Chiang Mai Basin, northern Thailand. Two profiles traversing the expected fault zone of soil gas radon measurements have been monitored, using TASTRAK solid state track nuclear detectors (SSNTDs). Radon signals from three periods of measurement show a distinctive consistent spatial distribution pattern. Anomalous radon areas along the profiles are connected to fault locations previously interpreted from other geophysical survey results. The increased radon signal changes from the radon background level with the signal-to-background ratio above 3 are considered anomalous. Such pattern of radon anomaly supports the existence of the faults. The radon measurement, therefore is a powerful technique in mapping active fault zone.

  1. On the pharmacology of ascending, descending and recurrent postsynatic inhibition of the cuneothalamic relay cells in the cat

    PubMed Central

    Kelly, J. S.; Renaud, L. P.

    1973-01-01

    1. In cats decerebrated or anaesthetized with pentobarbitone, cells of the middle third of the cuneate nucleus that were excited by tactile stimulation of the ipsilateral forelimb (responding to displacement of hairs, skin or joints) and inhibited by electrical stimulation of the contralateral pyramid, were invariably inhibited by electrical stimulation of the ipsilateral forepaw and the contralateral forelimb nerves. 2. In 50% of the cats, the cells were more fully identified by placing electrodes stereotaxically in the contralateral medial lemniscus. Recurrent inhibition was always a concomitant of the antidromic action potential. 3. The intensity and the duration of inhibition evoked by all of these pathways was totally resistant to iontophoretic and intravenous strychnine in doses at least 5 times that required to block completely the response of the same cells to iontophoretic glycine and was extremely sensitive to either iontophoretic bicuculline or picrotoxin. 4. Although the inhibition was invariably sensitive to intravenous picrotoxin, no significant change occurred in the duration or intensity of the inhibition when bicuculline was administered intravenously (5 or 6 times) as repeated doses of 0·2 mg/kg. 5. Postsynaptic inhibition in the cuneate may be mediated by γ-aminobutyric acid released from the nerve terminals of a common pool of interneurones shared by ascending, descending and recurrent pathways. Since the receptors involved in this pathway are resistant to intravenous bicuculline, they may well be distinct from those responsible for changes in the primary afferent terminal excitability, usually believed to be associated with presynaptic inhibition. PMID:4357959

  2. Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans.

    PubMed

    Lamy, Jean-Charles; Russmann, Heike; Shamim, Ejaz A; Meunier, Sabine; Hallett, Mark

    2010-08-01

    Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.

  3. Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

    PubMed

    Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

    2015-08-01

    Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

  4. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

    PubMed

    Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D

    2012-06-01

    Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. Wiley Periodicals, Inc.

  5. Contribution of irregular semicircular canal afferents to the horizontal vestibuloocular response during constant velocity rotation

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.; Perachio, A. A.

    1993-01-01

    1. The effects of constant anodal currents (100 microA) delivered bilaterally to both labyrinths on the horizontal vestibuloocular response (VOR) were studied in squirrel monkeys during steps of angular velocity in the dark. We report that bilateral anodal currents decreased eye velocity approximately 30-50% during the period of galvanic stimulation without a change in the time constant of VOR. The decrease in eye velocity, present during steps of angular velocity, was not observed during sinusoidal head rotation at 0.2, 0.5, and 1 Hz. The results suggest that responses from irregular vestibular afferents influence VOR amplitude during constant velocity rotation.

  6. Neurophysiology of the esophagus.

    PubMed

    Brock, Christina; Brokjaer, Anne; Drewes, Asbjørn Mohr; Farmer, Adam D; Frøkjaer, Jens Brøndum; Gregersen, Hans; Lottrup, Christian

    2014-09-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the methods and characteristics of esophageal afferents in humans; the pitfalls in characterization of mechanosensitive afferents; the sensitization of esophageal afferents in human studies; the brain source modeling in the understanding of the esophagus-brain axis; the use of evoked brain potentials in the esophagus; and measuring descending inhibition in animal and human studies. © 2014 New York Academy of Sciences.

  7. Spinal inhibition and motor function in adults with spastic cerebral palsy

    PubMed Central

    Condliffe, E. G.; Jeffery, D. T.; Emery, D. J.

    2016-01-01

    Key points Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy.Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction.In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord.In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants.These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity. Abstract Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post‐synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time‐locked to the occurrence of a sensory stimulation to produce peri‐stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF

  8. Unique processing during a period of high excitation/inhibition balance in adult-born neurons.

    PubMed

    Marín-Burgin, Antonia; Mongiat, Lucas A; Pardi, M Belén; Schinder, Alejandro F

    2012-03-09

    The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.

  9. Ia Afferent input alters the recruitment thresholds and firing rates of single human motor units.

    PubMed

    Grande, G; Cafarelli, E

    2003-06-01

    Vibration of the patellar tendon recruits motor units in the knee extensors via excitation of muscle spindles and subsequent Ia afferent input to the alpha-motoneuron pool. Our first purpose was to determine if the recruitment threshold and firing rate of the same motor unit differed when recruited involuntarily via reflex or voluntarily via descending spinal pathways. Although Ia input is excitatory to the alpha-motoneuron pool, it has also been shown paradoxically to inhibit itself. Our second purpose was to determine if vibration of the patellar tendon during a voluntary knee extension causes a change in the firing rate of already recruited motor units. In the first protocol, 10 subjects voluntarily reproduced the same isometric force profile of the knee extensors that was elicited by vibration of the patellar tendon. Single motor unit recordings from the vastus lateralis (VL) were obtained with tungsten microelectrodes and unitary behaviour was examined during both reflex and voluntary knee extensions. Recordings from 135 single motor units showed that both recruitment thresholds and firing rates were lower during reflex contractions. In the second protocol, 7 subjects maintained a voluntary knee extension at 30 N for approximately 40-45 s. Three bursts of patellar tendon vibration were superimposed at regular intervals throughout the contraction and changes in the firing rate of already recruited motor units were examined. A total of 35 motor units were recorded and each burst of superimposed vibration caused a momentary reduction in the firing rates and recruitment of additional units. Our data provide evidence that Ia input modulates the recruitment thresholds and firing rates of motor units providing more flexibility within the neuromuscular system to grade force at low levels of force production.

  10. The effect of propofol on CA1 pyramidal cell excitability and GABAA-mediated inhibition in the rat hippocampal slice.

    PubMed

    Albertson, T E; Walby, W F; Stark, L G; Joy, R M

    1996-05-24

    An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of propofol on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid, and electrodes were placed in the CA1 region to record extracellular field population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. The major effect of propofol (7-28 microM) was a dose and time dependent increase in the intensity and duration of GABA-mediated inhibition. This propofol effect could be rapidly and completely reversed by exposure to known GABAA antagonists, including picrotoxin, bicuculline and pentylenetetrazol. It was also reversed by the chloride channel antagonist, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was not antagonized by central (flumazenil) or peripheral (PK11195) benzodiazepine antagonists. Reversal of endogenous inhibition was also noted with the antagonists picrotoxin and pentylenetetrazol. Input/output curves constructed using stimulus propofol caused only a small enhancement of EPSPs at higher stimulus intensities but had no effect on PS amplitudes. These studies are consistent with propofol having a GABAA-chloride channel mechanism causing its effect on recurrent collateral evoked inhibition in the rat hippocampal slice.

  11. Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.

    PubMed

    Yagüe, Sara; Veciana, Misericordia; Casasnovas, Carlos; Ruiz, Montserrat; Pedro, Jordi; Valls-Solé, Josep; Pujol, Aurora

    2018-03-01

    Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition. In 13 adrenomyeloneuropathic patients we examined LEPs to leg, arm and face stimulation. Normative data were obtained from 10 healthy subjects examined in the same experimental conditions. We also examined brainstem auditory evoked potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs). Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4 patients (30.7%) and the leg in 10 patients (76.9%). The pathologic process of adrenomyeloneuropathy is characterized by a preferential involvement of auditory, motor and somatosensory tracts and less severely of the visual and nociceptive pathways. This non-inflammatory distal axonopathy preferably damages large myelinated spinal tracts but there is also partial involvement of small myelinated fibres. LEPs studies can provide relevant information about afferent pain pathways involvement in adrenomyeloneuropathic patients. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. State-space receptive fields of semicircular canal afferent neurons in the bullfrog

    NASA Technical Reports Server (NTRS)

    Paulin, M. G.; Hoffman, L. F.

    2001-01-01

    Receptive fields are commonly used to describe spatial characteristics of sensory neuron responses. They can be extended to characterize temporal or dynamical aspects by mapping neural responses in dynamical state spaces. The state-space receptive field of a neuron is the probability distribution of the dynamical state of the stimulus-generating system conditioned upon the occurrence of a spike. We have computed state-space receptive fields for semicircular canal afferent neurons in the bullfrog (Rana catesbeiana). We recorded spike times during broad-band Gaussian noise rotational velocity stimuli, computed the frequency distribution of head states at spike times, and normalized these to obtain conditional pdfs for the state. These state-space receptive fields quantify what the brain can deduce about the dynamical state of the head when a single spike arrives from the periphery. c2001 Elsevier Science B.V. All rights reserved.

  13. Breadth of tuning in taste afferent neurons varies with stimulus strength

    PubMed Central

    Wu, An; Dvoryanchikov, Gennady; Pereira, Elizabeth; Chaudhari, Nirupa; Roper, Stephen D.

    2015-01-01

    Gustatory stimuli are detected by taste buds and transmitted to the hindbrain via sensory afferent neurons. Whether each taste quality (sweet, bitter and so on) is encoded by separate neurons (‘labelled lines') remains controversial. We used mice expressing GCaMP3 in geniculate ganglion sensory neurons to investigate taste-evoked activity. Using confocal calcium imaging, we recorded responses to oral stimulation with prototypic taste stimuli. Up to 69% of neurons respond to multiple tastants. Moreover, neurons tuned to a single taste quality at low concentration become more broadly tuned when stimuli are presented at higher concentration. Responses to sucrose and monosodium glutamate are most related. Although mice prefer dilute NaCl solutions and avoid concentrated NaCl, we found no evidence for two separate populations of sensory neurons that encode this distinction. Altogether, our data suggest that taste is encoded by activity in patterns of peripheral sensory neurons and challenge the notion of strict labelled line coding. PMID:26373451

  14. Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.

    PubMed

    Schelegle, E S; Walby, W F; Mansoor, J K; Chen, A T

    2001-05-01

    Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

  15. Afferent projections to the mammillary complex of the rat, with special reference to those from surrounding hypothalamic regions

    NASA Technical Reports Server (NTRS)

    Gonzalo-Ruiz, A.; Alonso, A.; Sanz, J. M.; Llinas, R. R.

    1992-01-01

    To better understand the functional organization of the mammillary nuclei, we investigated the afferents to this nuclear complex in the rat with iontophoretically injected wheat germ agglutinin conjugated to horseradish peroxidase. Particular attention was paid to tracing local hypothalamic afferents to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed strong projections from the subicular region, and weaker projections from the prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca. Other descending subcortical projections to the MMN arise from the anterior and the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of the stria terminalis. Ascending afferents to the MMN were found to originate in the raphe and various tegmental nuclei. Following all injections into the MMN, labelled neurons were found in nuclei surrounding the mammillary body. The lateral and posterior subdivisions of the tuberomammillary nucleus projected mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral premammillary nuclei projected to the pars lateralis of the MMN. The supramammillary nucleus at rostral level had a small projection to the pars medialis and lateralis of the MMN. However, the most obvious projection from this nucleus was to the pars posterior of the MMN, chiefly from the lateral part of the caudal supramammillary nucleus. Injections into the lateral mammillary nucleus revealed inputs from the presubiculum, parasubiculum, septal region, dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In addition, the lateral mammillary nucleus was found to receive a moderate projection from the medial part of the supramammillary nucleus and stronger projections from the lateral part of the caudal supramammillary nucleus. A very light projection was also seen from the lateral and posterior subdivisions of the tuberomammillary nucleus. These findings add to our knowledge

  16. Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fisone, G.; Wu, C.F.; Consolo, S.

    1987-10-01

    A high density of galanin binding sites was found by using /sup 125/I-labeled galanin, iodinated by chloramine-T, followed by autoradiography in the ventral, but not in the dorsal, hippocampus of the rat. Lesions of the fimbria and of the septum caused disappearance of a major population of these binding sites, suggesting that a large proportion of them is localized on cholinergic nerve terminals of septal afferents. As a functional correlate to these putative galanin receptor sites, it was shown, both in vivo and in vitro, that galanin, in a concentration-dependent manner, inhibited the evoked release of acetylcholine in the ventral,more » but not in the dorsal, hippocampus. Intracerebroventricularly applied galanin fully inhibited the scopolamine stimulated release of acetylcholine in the ventral, but not in the dorsal, hippocampus, as measured by the microdialysis technique. In vitro, galanin inhibited the 25 mM K/sup +/-evoked release of (/sup 3/H)acetylcholine from slices of the ventral hippocampus, with an IC/sub 50/ value of approx. = 50 nM. These results are discussed with respect to the colocalization of galanin- and choline acetyltransferase-like immunoreactivity in septal somata projecting to the hippocampus.« less

  17. Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

    PubMed Central

    Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D.

    2012-01-01

    Objective Previous Vagus Nerve Stimulation (VNS) studies have demonstrated anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or t-VNS, have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design counterbalanced, crossover study. Patients patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes We evaluated evoked pain analgesia for Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) compared with Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one week apart. Outcome measures included deep tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. PMID:22568773

  18. Effect of afferent feedback and central motor commands on soleus H-reflex suppression during arm cycling.

    PubMed

    Hundza, S R; de Ruiter, Geoff C; Klimstra, M; Zehr, E Paul

    2012-12-01

    Suppression of soleus H-reflex amplitude in stationary legs is seen during rhythmic arm cycling. We examined the influence of various arm-cycling parameters on this interlimb reflex modulation to determine the origin of the effect. We previously showed the suppression to be graded with the frequency of arm cycling but not largely influenced by changes in peripheral input associated with crank length. Here, we more explicitly explored the contribution of afferent feedback related to arm movement on the soleus H-reflex suppression. We explored the influence of load and rate of muscle stretch by manipulating crank-load and arm-muscle vibration during arm cycling. Furthermore, internally driven ("Active") and externally driven ("Passive") arm cycling was compared. Soleus H-reflexes were evoked with tibial nerve stimulation during stationary control and rhythmic arm-cycling conditions, including: 1) six different loads; 2) with and without vibration to arm muscles; and 3) Active and Passive conditions. No significant differences were seen in the level of suppression between the different crank loads or between conditions with and without arm-muscle vibration. Furthermore, in contrast to the clear effect seen during active cycling, passive arm cycling did not significantly suppress the soleus H-reflex amplitude. Current results, in conjunction with previous findings, suggest that the afferent feedback examined in these studies is not the primary source responsible for soleus H-reflex suppression. Instead, it appears that central motor commands (supraspinal or spinal in origin) associated with frequency of arm cycling are relatively more dominant sources.

  19. Afference copy as a quantitative neurophysiological model for consciousness.

    PubMed

    Cornelis, Hugo; Coop, Allan D

    2014-06-01

    Consciousness is a topic of considerable human curiosity with a long history of philosophical analysis and debate. We consider there is nothing particularly complicated about consciousness when viewed as a necessary process of the vertebrate nervous system. Here, we propose a physiological "explanatory gap" is created during each present moment by the temporal requirements of neuronal activity. The gap extends from the time exteroceptive and proprioceptive stimuli activate the nervous system until they emerge into consciousness. During this "moment", it is impossible for an organism to have any conscious knowledge of the ongoing evolution of its environment. In our schematic model, a mechanism of "afference copy" is employed to bridge the explanatory gap with consciously experienced percepts. These percepts are fabricated from the conjunction of the cumulative memory of previous relevant experience and the given stimuli. They are structured to provide the best possible prediction of the expected content of subjective conscious experience likely to occur during the period of the gap. The model is based on the proposition that the neural circuitry necessary to support consciousness is a product of sub/preconscious reflexive learning and recall processes. Based on a review of various psychological and neurophysiological findings, we develop a framework which contextualizes the model and briefly discuss further implications.

  20. Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of bladder afferent pathways in spinal cord injured rats.

    PubMed

    Matsumoto, Yoshihiro; Miyazato, Minoru; Yokoyama, Hitoshi; Kita, Masafumi; Hirao, Yoshihiko; Chancellor, Michael B; Yoshimura, Naoki

    2012-05-01

    To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. "Syndrome in syndrome": Wernicke syndrome due to afferent loop syndrome. Case report and review of the literature.

    PubMed

    D'Abbicco, D; Praino, S; Amoruso, M; Notarnicola, A; Margari, A

    2011-01-01

    Wernicke syndrome is a rare neurological pathology due to a deficit in vitamin B1. The syndrome is common among alcohol abusers, patients with malignant tumor or gastrointestinal diseases, those who undergo hemodialysis or long-term peritoneal dialysis, pregnant women with hyperemesis, women who breast-feed, patients with hyperthyroidism or anorexia nervosa or gastric or jejunal-ileal bypass surgery for obesity, patients submitted to gastric surgery or prolonged total parenteral nutrition or prolonged intravenous therapy. We report a case of Wernicke syndrome due to afferent loop syndrome characterized by incoercible vomiting.

  2. Primary afferent depolarization and changes in extracellular potassium concentration induced by L-glutamate and L-proline in the isolated spinal cord of the frog.

    PubMed

    Vyklický, L; Vyskocil, F; Kolaj, M; Jastreboff, P

    1982-10-08

    To test the hypothesis that L-proline acts as an antagonist on glutamate receptors [17, 18], the interaction between L-glutamate and L-proline was studied in the isolated spinal cord of the frog. Glutamate at concentrations of 10(-6) -5 x 10(-3) mol/l depolarized the primary afferent fibres and increased extracellular potassium concentration, [K+]e, by 0.3-4 mmol/l. Repeated applications lead to inactivation of the response. L-Proline at 5 x 10(-3) -10(-2) mol/l, also depolarized the primary afferents and increased [K+]e by 0.5-2 mmol/l, but there was only a slight decrease of the effects after repeated application. The effects were additive when the amino acids were applied simultaneously. The effect of L-proline was still present when it was applied during inactivation of the glutamate receptors. This suggests that L-glutamate and L-proline act on different receptors.

  3. Bronchoconstriction induced by hyperventilation with humidified hot air: role of TRPV1-expressing airway afferents.

    PubMed

    Lin, Ruei-Lung; Hayes, Don; Lee, Lu-Yuan

    2009-06-01

    A recent study by our laboratory has shown that an increase in intrathoracic temperature activates vagal pulmonary C-fibers. Because these afferents are known to elicit reflex bronchoconstriction upon stimulation, this study was carried out to investigate if an increase in airway temperature within the physiological range alters bronchomotor tone. Adult guinea pigs were anesthetized and mechanically ventilated via a tracheal tube. After the lung had been hyperventilated with humidified hot air (HHA) for 4 min, the tracheal temperature was elevated from 36.4 to 40.5 degrees C, which induced an immediate bronchoconstriction, increasing total pulmonary resistance (R(L)) to 177 +/- 10% and decreasing dynamic lung compliance to 81 +/- 6% of their respective baselines. The increase in R(L) returned spontaneously toward the baseline in <10 min and was reproducible in the same animals. There were no difference in the responses whether the humidity was generated from distilled water or isotonic saline. In contrast, hyperventilation with humidified air at room temperature did not cause any increase in R(L). The increase in R(L) caused by HHA was attenuated by 65.9% after a pretreatment with atropine alone and by 72.0% after a pretreatment with a combination of atropine and neurokinin receptor type 1 and 2 antagonists. In addition, capsazepine, a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, reduced the HHA-induced increase in R(L) by 64.1% but did not abolish it. However, pretreatment with formoterol, a beta(2)-agonist, completely prevented the HHA-induced bronchoconstriction. These results indicate that the increase in airway temperature induced transient airway constriction in guinea pigs. Approximately two-thirds of the increase in bronchomotor tone was mediated through the cholinergic reflex, which was probably elicited by the activation of TRPV1-expressing airway afferents. The remaining bronchoconstriction was caused by other, yet

  4. Continuous detection of weak sensory signals in afferent spike trains: the role of anti-correlated interspike intervals in detection performance.

    PubMed

    Goense, J B M; Ratnam, R

    2003-10-01

    An important problem in sensory processing is deciding whether fluctuating neural activity encodes a stimulus or is due to variability in baseline activity. Neurons that subserve detection must examine incoming spike trains continuously, and quickly and reliably differentiate signals from baseline activity. Here we demonstrate that a neural integrator can perform continuous signal detection, with performance exceeding that of trial-based procedures, where spike counts in signal- and baseline windows are compared. The procedure was applied to data from electrosensory afferents of weakly electric fish (Apteronotus leptorhynchus), where weak perturbations generated by small prey add approximately 1 spike to a baseline of approximately 300 spikes s(-1). The hypothetical postsynaptic neuron, modeling an electrosensory lateral line lobe cell, could detect an added spike within 10-15 ms, achieving near ideal detection performance (80-95%) at false alarm rates of 1-2 Hz, while trial-based testing resulted in only 30-35% correct detections at that false alarm rate. The performance improvement was due to anti-correlations in the afferent spike train, which reduced both the amplitude and duration of fluctuations in postsynaptic membrane activity, and so decreased the number of false alarms. Anti-correlations can be exploited to improve detection performance only if there is memory of prior decisions.

  5. Using vertebral movement and intact paraspinal muscles to determine the distribution of intrafusal fiber innervation of muscle spindle afferents in the anesthetized cat.

    PubMed

    Reed, William R; Cao, Dong-Yuan; Ge, Weiqing; Pickar, Joel G

    2013-03-01

    Increasing our knowledge regarding intrafusal fiber distribution and physiology of paraspinal proprioceptors may provide key insights regarding proprioceptive deficits in trunk control associated with low back pain and lead to more effective clinical intervention. The use of vertebral movement as a means to reliably stretch paraspinal muscles would greatly facilitate physiological study of paraspinal muscle proprioceptors where muscle tendon isolation is either very difficult or impossible. The effects of succinylcholine (SCh) on 194 muscle spindle afferents from lumbar longissimus or multifidus muscles in response to computer-controlled, ramp-and-hold movements of the L(6) vertebra were investigated in anesthetized cats. Paraspinal muscles were stretched by moving the L(6) vertebra 1.5-1.7 mm in the dorsal-ventral direction. Initial frequency (IF), dynamic difference (DD), their changes (∆) following SCh injection (100-400 μg kg(-1)), and post-SCh dynamic difference (SChDD) were measured. Muscle spindle intrafusal fiber terminations were classified as primary or secondary fibers as well as bag(1) (b(1)c), bag(2) (b(2)c), b(1)b(2)c, or chain (c) fibers. Intrafusal fiber subpopulations were distinguished using logarithmic transformation of SChDD and ∆IF distributions as established by previous investigators. Increases in DD indicate strength of b(1)c influence while increases in IF indicate strength of b(2)c influence. Out of 194 afferents, 46.9 % of afferents terminated on b(2)c fibers, 46.4 % on b(1)b(2)c fibers, 1 % on b(1)c fibers, and 5.7 % terminated on c fibers. Based on these intrafusal fiber subpopulation distributions, controlled vertebral movement can effectively substitute for direct tendon stretch and allow further investigation of paraspinal proprioceptors in this anatomically complex body region.

  6. Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough

    PubMed Central

    Morris, Kendall F.; Segers, Lauren S.; Poliacek, Ivan; Rose, Melanie J.; Lindsey, Bruce G.; Davenport, Paul W.; Howland, Dena R.; Bolser, Donald C.

    2016-01-01

    We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter and shape afferent input to the respiratory network during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is variable: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for this dynamic feature of a repetitive cough bout. When a single second-order population was split into two subpopulations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing had less variance than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited increased variance in the expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough. PMID:27283917

  7. Urban renewal based wind environment at pedestrian level in high-density and high-rise urban areas in Sai Ying Pun, Hong Kong

    NASA Astrophysics Data System (ADS)

    Yao, J. W.; Zheng, J. Y.; Zhao, Y.; Shao, Y. H.; Yuan, F.

    2017-11-01

    In high-density and high-rise urban areas, pedestrian level winds contribute to improve comfort, safety and diffusion of heat in urban areas. Outdoor wind study is extremely vital and a prerequisite in high-density cities considering that the immediate pedestrian level wind environment is fundamentally impacted by the presence of a series of high-rise buildings. In this paper, the research site of Sai Ying Pun in Hong Kong will be analysed in terms of geography, climate and urban morphology, while the surrounding natural ventilation has also been simulated by the wind tunnel experiment Computational Fluid Dynamics (CFD). It has found that, the existing problems in this district are the contradiction between planning control and commercial interests, which means some areas around tall buildings are not benefit to the residents because of the unhealthy wind environment. Therefore, some recommendation of urban renewal strategy has been provided.

  8. TERMINAL ARBORS OF AXONS PROJECTING TO THE SOMATOSENSORY CORTEX OF THE ADULT RAT. 2. THE ALTERED MORPHOLOGY OF THALAMOCORTICAL AFFERENTS FOLLOWING NEONATAL INFRAORBITAL NERVE CUT (JOURNAL VERSION)

    EPA Science Inventory

    The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in the cortical map arise the authors examined the organization of thalamocortical afferents to the whiske...

  9. A new model of strabismic amblyopia: Loss of spatial acuity due to increased temporal dispersion of geniculate X-cell afferents on to cortical neurons.

    PubMed

    Crewther, D P; Crewther, S G

    2015-09-01

    Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation

    PubMed Central

    Holtzman, Tahl; Jörntell, Henrik

    2011-01-01

    Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex. PMID:22046297

  11. CHRONIC HYPERTENSION ENHANCES PRE-SYNAPTIC INHIBITION BY BACLOFEN IN THE NUCLEUS OF THE SOLITARY TRACT

    PubMed Central

    Zhang, Weirong; Mifflin, Steve

    2010-01-01

    The selective γ-aminobutyric acid B-subtype receptor agonist baclofen activates both pre- and post-synaptic receptors in the brain. Microinjection of baclofen into the nucleus of the solitary tract increases arterial pressure, heart rate and sympathetic nerve discharge consistent with inhibition of the arterial baroreflex. The magnitude of these responses is enhanced in hypertension and is associated with increased post-synaptic GABAB receptor function. We tested whether a pre-synaptic mechanism contributes to the enhanced baclofen inhibition in hypertension. Whole-cell recordings of second-order baroreceptor neurons, identified by 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide labeling of aortic nerve, were obtained in brainstem slices from normotensive control and renal-wrap hypertensive rats. After 4 weeks, arterial blood pressure was 162±9 mmHg in hypertensive (n=6) and 107±3 mmHg in control rats (n=6/11, p<0.001). Baclofen reduced the amplitude of excitatory post-synaptic currents evoked by solitary tract stimulation and the EC50 of this inhibition was greater in control (1.5±0.5 µmol/L, n=6) than hypertensive cells (0.6±0.1 µmol/L, n=9, p<0.05). Baclofen (1 µmol/L) elicited greater inhibition on evoked response in hypertensive (58±6%, n=9) than control cells (40±6%, n=8, p<0.05). Another index of pre-synaptic inhibition, the paired-pulse ratio (ratio of second to first evoked response amplitudes at stimulus intervals of 40 ms), was greater in hypertensive (0.60±0.08, n=8) than control cells (0.48±0.06. n=5, p<0.05). The results suggest that in renal-wrap hypertensive rats, baclofen causes an enhanced pre-synaptic inhibition of glutamate release from baroreceptor afferent terminals to second-order neurons in the nucleus of the solitary tract. This enhanced pre-synaptic inhibition could contribute to altered baroreflex function in hypertension. PMID:20038748

  12. Distinct Expression of Phenotypic Markers in Placodes- and Neural Crest-Derived Afferent Neurons Innervating the Rat Stomach.

    PubMed

    Trancikova, Alzbeta; Kovacova, Eva; Ru, Fei; Varga, Kristian; Brozmanova, Mariana; Tatar, Milos; Kollarik, Marian

    2018-02-01

    Visceral pain is initiated by activation of primary afferent neurons among which the capsaicin-sensitive (TRPV1-positive) neurons play an important role. The stomach is a common source of visceral pain. Similar to other organs, the stomach receives dual spinal and vagal afferent innervation. Developmentally, spinal dorsal root ganglia (DRG) and vagal jugular neurons originate from embryonic neural crest and vagal nodose neurons originate from placodes. In thoracic organs the neural crest- and placodes-derived TRPV1-positive neurons have distinct phenotypes differing in activation profile, neurotrophic regulation and reflex responses. It is unknown to whether such distinction exists in the stomach. We hypothesized that gastric neural crest- and placodes-derived TRPV1-positive neurons express phenotypic markers indicative of placodes and neural crest phenotypes. Gastric DRG and vagal neurons were retrogradely traced by DiI injected into the rat stomach wall. Single-cell RT-PCR was performed on traced gastric neurons. Retrograde tracing demonstrated that vagal gastric neurons locate exclusively into the nodose portion of the rat jugular/petrosal/nodose complex. Gastric DRG TRPV1-positive neurons preferentially expressed markers PPT-A, TrkA and GFRα 3 typical for neural crest-derived TRPV1-positive visceral neurons. In contrast, gastric nodose TRPV1-positive neurons preferentially expressed markers P2X 2 and TrkB typical for placodes-derived TRPV1-positive visceral neurons. Differential expression of neural crest and placodes markers was less pronounced in TRPV1-negative DRG and nodose populations. There are phenotypic distinctions between the neural crest-derived DRG and placodes-derived vagal nodose TRPV1-positive neurons innervating the rat stomach that are similar to those described in thoracic organs.

  13. Atomoxetine restores the response inhibition network in Parkinson’s disease

    PubMed Central

    Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson’s disease. PMID:27343257

  14. The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse

    PubMed Central

    Becker, Lars; Schnee, Michael E; Niwa, Mamiko; Sun, Willy; Maxeiner, Stephan; Talaei, Sara; Kachar, Bechara; Rutherford, Mark A

    2018-01-01

    The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon’s contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles. PMID:29328021

  15. After-effects of peripheral neurostimulation on brain plasticity and ankle function in chronic stroke: The role of afferents recruited.

    PubMed

    Beaulieu, Louis-David; Massé-Alarie, Hugo; Camiré-Bernier, Samuel; Ribot-Ciscar, Édith; Schneider, Cyril

    2017-09-01

    This study tested the after-effects of neuromuscular electrical stimulation (NMES), repetitive peripheral magnetic stimulation (rPMS) and muscle tendon vibration (VIB) on brain plasticity and sensorimotor impairments in chronic stroke to investigate whether different results could depend on the nature of afferents recruited by each technique. Fifteen people with chronic stroke participated in five sessions (one per week). Baseline measures were collected in session one, then, each participant received 4 randomly ordered interventions (NMES, rPMS, VIB and a 'control' intervention of exercises). Interventions were applied to the paretic ankle muscles and parameters of application were matched as closely as possible. Standardized clinical measures of the ankle function on the paretic side and transcranial magnetic stimulation (TMS) outcomes of both primary motor cortices (M1) were collected at pre- and post-application of each intervention. The ankle muscle strength was significantly improved by rPMS and VIB (P≤0.02). rPMS influenced M1 excitability (increase in the contralesional hemisphere, P=0.03) and inhibition (decrease in both hemispheres, P≤0.04). The group mean of a few clinical outcomes improved across sessions, i.e. independently of the order of interventions. Some TMS outcomes at baseline could predict the responsiveness to rPMS and VIB. This original study suggests that rPMS and VIB were efficient to drive M1 plasticity and sensorimotor improvements, likely via massive inflows of 'pure' proprioceptive information generated. Usefulness of some TMS outcomes to predict which intervention a patient could be more responsive to should be further tested in future studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat.

    PubMed

    Li, Jin-Lian; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

    2003-03-10

    We examined immunohistochemically whether the vesicular glutamate transporters (VGluTs), VGluT1 and VGluT2, might be expressed in synaptic terminals of nociceptive primary afferent fibers within laminae I and II of the medullary and spinal dorsal horns of the rat. VGluT1 immunoreactivity (IR) was intense in the inner part of lamina II but weak in lamina I and the outer part of lamina II. VGluT2-IR was most intense in lamina I and the outer part of lamina II. Expression of VGluTs in synaptic terminals was confirmed by dual immunofluorescence histochemistry for VGluTs and synaptophysin. Expression of VGluTs in axon terminals of primary afferent fibers terminating in laminae I and II was also confirmed immunohistochemically after unilateral dorsal rhizotomy. The dual immunofluorescence histochemistry indicated expression of VGluTs in substance P (SP)-containing axon terminals in lamina I and the outer part of lamina II. Electron microscopy confirmed the coexpression of VGluTs and SP in axon terminals within laminae I and II; VGluTs was associated with round synaptic vesicles at the asymmetric synapses. It was further observed that isolectin IB4, a marker for unmyelinated axons, often bound with VGluT2-immunopositive structures but rarely with VGluT1-immunopositive structures in lamina II. Thus, the results indicated in laminae I and II of the medullary and spinal dorsal horns that both VGluT1 and VGluT2 were expressed in axon terminals of primary afferent fibers, including SP-containing nociceptive fibers and that VGluT in unmyelinated primary afferent fibers terminating in lamina II was primarily VGluT2. Copyright 2003 Wiley-Liss, Inc.

  17. Atomoxetine restores the response inhibition network in Parkinson's disease.

    PubMed

    Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-08-01

    time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

  18. Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

    PubMed

    Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

    1987-07-01

    The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

  19. Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough.

    PubMed

    Pitts, Teresa; Morris, Kendall F; Segers, Lauren S; Poliacek, Ivan; Rose, Melanie J; Lindsey, Bruce G; Davenport, Paul W; Howland, Dena R; Bolser, Donald C

    2016-07-01

    We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter and shape afferent input to the respiratory network during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is variable: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for this dynamic feature of a repetitive cough bout. When a single second-order population was split into two subpopulations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing had less variance than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited increased variance in the expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough. Copyright © 2016 the American Physiological Society.

  20. Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

    PubMed Central

    Burton, Shawn D.

    2015-01-01

    Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE

  1. Muscle spindle thixotropy affects force perception through afferent-induced facilitation of the motor pathways as revealed by the Kohnstamm effect.

    PubMed

    Monjo, Florian; Forestier, Nicolas

    2018-04-01

    This study was designed to explore the effects of intrafusal thixotropy, a property affecting muscle spindle sensitivity, on the sense of force. For this purpose, psychophysical measurements of force perception were performed using an isometric force matching paradigm of elbow flexors consisting of matching different force magnitudes (5, 10 and 20% of subjects' maximal voluntary force). We investigated participants' capacity to match these forces after their indicator arm had undergone voluntary isometric conditioning contractions known to alter spindle thixotropy, i.e., contractions performed at long ('hold long') or short muscle lengths ('hold short'). In parallel, their reference arm was conditioned at the intermediate muscle length ('hold-test') at which the matchings were performed. The thixotropy hypothesis predicts that estimation errors should only be observed at low force levels (up to 10% of the maximal voluntary force) with overestimation of the forces produced following 'hold short' conditioning and underestimation following 'hold long' conditioning. We found the complete opposite, especially following 'hold-short' conditioning where subjects underestimated the force they generated with similar relative error magnitudes across force levels. In a second experiment, we tested the hypothesis that estimation errors depended on the degree of afferent-induced facilitation using the Kohnstamm phenomenon as a probe of motor pathway excitability. Because the stronger post-effects were observed following 'hold-short' conditioning, it appears that the conditioning-induced excitation of spindle afferents leads to force misjudgments by introducing a decoupling between the central effort and the cortical motor outputs.

  2. Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

    PubMed

    Wang, H F; Shortland, P; Park, M J; Grant, G

    1998-11-01

    In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with

  3. NEUROTROPHIN SELECTIVITY IN ORGANIZING TOPOGRAPHIC REGENERATION OF NOCICEPTIVE AFFERENTS

    PubMed Central

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M.

    2015-01-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP+) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4+ non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFR-α3, which only promoted mistargeted regeneration. PMID:26054884

  4. Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.

    PubMed

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M

    2015-09-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP(+)) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4(+) non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFRα3, which only promoted mistargeted regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Afferents to the Orexin Neurons of the Rat Brain

    PubMed Central

    YOSHIDA, KYOKO; McCORMACK, SARAH; ESPAÑA, RODRIGO A.; CROCKER, AMANDA; SCAMMELL, THOMAS E.

    2008-01-01

    Emotions, stress, hunger, and circadian rhythms all promote wakefulness and behavioral arousal. Little is known about the pathways mediating these influences, but the orexin-producing neurons of the hypothalamus may play an essential role. These cells heavily innervate many wake-promoting brain regions, and mice lacking the orexin neurons have narcolepsy and fail to rouse in response to hunger (Yamanaka et al. [2003] Neuron 38:701–713). To identify the afferents to the orexin neurons, we first injected a retrograde tracer into the orexin neuron field of rats. Retrogradely labeled neurons were abundant in the allocortex, claustrum, lateral septum, bed nucleus of the stria terminalis, and in many hypothalamic regions including the preoptic area, dorsomedial nucleus, lateral hypothalamus, and posterior hypothalamus. Retrograde labeling in the brainstem was generally more modest, but labeling was strong in the periaqueductal gray matter, dorsal raphe nucleus, and lateral parabrachial nucleus. Injection of an anterograde tracer confirmed that most of these regions directly innervate the orexin neurons, with some of the heaviest input coming from the lateral septum, preoptic area, and posterior hypothalamus. In addition, hypothalamic regions preferentially innervate orexin neurons in the medial and perifornical parts of the field, but most projections from the brainstem target the lateral part of the field. Inputs from the suprachiasmatic nucleus are mainly relayed via the subparaventricular zone and dorsomedial nucleus. These observations suggest that the orexin neurons may integrate a variety of interoceptive and homeostatic signals to increase behavioral arousal in response to hunger, stress, circadian signals, and autonomic challenges. PMID:16374809

  6. Neurogenic vasodilatation and plasma leakage in the skin.

    PubMed

    Holzer, P

    1998-01-01

    1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.

  7. Auditory perception in the aging brain: the role of inhibition and facilitation in early processing.

    PubMed

    Stothart, George; Kazanina, Nina

    2016-11-01

    Aging affects the interplay between peripheral and cortical auditory processing. Previous studies have demonstrated that older adults are less able to regulate afferent sensory information and are more sensitive to distracting information. Using auditory event-related potentials we investigated the role of cortical inhibition on auditory and audiovisual processing in younger and older adults. Across puretone, auditory and audiovisual speech paradigms older adults showed a consistent pattern of inhibitory deficits, manifested as increased P50 and/or N1 amplitudes and an absent or significantly reduced N2. Older adults were still able to use congruent visual articulatory information to aid auditory processing but appeared to require greater neural effort to resolve conflicts generated by incongruent visual information. In combination, the results provide support for the Inhibitory Deficit Hypothesis of aging. They extend previous findings into the audiovisual domain and highlight older adults' ability to benefit from congruent visual information during speech processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Development of vestibular afferent projections into the hindbrain and their central targets

    NASA Technical Reports Server (NTRS)

    Maklad, Adel; Fritzsch, Bernd

    2003-01-01

    In contrast to most other sensory systems, hardly anything is known about the neuroanatomical development of central projections of primary vestibular neurons and how their second order target neurons develop. Recent data suggest that afferent projections may develop not unlike other sensory systems, forming first the overall projection by molecular means followed by an as yet unspecified phase of activity mediated refinement. The latter aspect has not been tested critically and most molecules that guide the initial projection are unknown.The molecular and topological origin of the vestibular and cochlear nucleus neurons is also only partially understood. Auditory and vestibular nuclei form from several rhombomeres and a given rhombomere can contribute to two or more auditory or vestibular nuclei. Rhombomere compartments develop as functional subdivisions from a single column that extends from the hindbrain to the spinal cord. Suggestions are provided for the molecular origin of these columns but data on specific mutants testing these proposals are not yet available. Overall, the functional significance of both overlapping and segregated projections are not yet fully experimentally explored in mammals. Such lack of details of the adult organization compromises future developmental analysis.

  9. [Functional properties of taste bud cells. Mechanisms of afferent neurotransmission in Type II taste receptor cells].

    PubMed

    Romanov, R A

    2013-01-01

    Taste Bud cells are heterogeneous in their morphology and functionality. These cells are responsible for sensing a wide variety of substances and for associating detected compounds with a different taste: bitter, sweet, salty, sour and umami. Today we know that each of the five basic tastes corresponds to distinct cell populations organized into three basic morpho-functional cell types. In addition, some receptor cells of the taste bud demonstrate glia-related functions. In this article we expand on some properties of these three morphological receptor cell types. Main focus is devoted to the Type II cells and unusual mechanism for afferent neurotransmission in these cells. Taste cells of the Type II consist of three populations detecting bitter, sweet and umami tastes, and, thus, evoke a serious scientific interest.

  10. Partial transformation from fast to slow muscle fibers induced by deafferentation of capsaicin-sensitive muscle afferents.

    PubMed

    Brunetti, O; Barazzoni, A M; Della Torre, G; Clavenzani, P; Pettorossi, V E; Bortolami, R

    1997-11-01

    Mechanical and histochemical characteristics of the lateral gastrocnemius (LG) muscle of the rat were examined 21 days after capsaicin injection into the LG muscle. The capsaicin caused a decrease in generation rate of twitch and tetanic tension and an increase in fatigue resistance of LG muscle. The histochemical muscle fiber profile evaluated by myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide tetrazolium reductase methods showed an increase of type I and IIC fibers and a decrease of the type IIB in whole muscle, and a decrease of the IIA, IIX fibers in the red part accompanied by their increase in the white part. Therefore the capsaicin treatment, which selectively eliminated fibers belonging to the III and IV groups of muscle afferents, induced muscle fiber transformation from fast contracting fatiguing fibers to slowly contracting nonfatiguing ones.

  11. Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell excitability in the rat hippocampal slice.

    PubMed

    Joy, R M; Walby, W F; Stark, L G; Albertson, T E

    1995-01-01

    An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed analyses of the effects of lindane. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. Perfusion with lindane produced both time and dose dependent changes in a number of the responses measured. The most striking effect produced by lindane was the loss of GABAA-mediated recurrent collateral inhibition. This tended to occur rapidly, often before changes in EPSP or PS responses could be detected. With longer exposures to lindane, repetitive discharge of pyramidal cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM) also completely reversed the effects of the injectable anesthetic, propofol, a compound known to potentiate GABAA-mediated inhibition via a direct action on the GABAA receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed that lindane increased EPSP and PS response amplitudes at any given stimulus intensity resulting in a leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low intensity stimuli and became progressively less so as stimulus intensities approached those yielding maximal responses. In addition lindane significantly increased paired pulse

  12. Vigilance, sleep and epilepsy.

    PubMed

    Vieth, J

    1986-01-01

    The correlations between vigilance and epilepsy are manifold. Nearly all epileptic seizures cause a diminution of vigilance extending to unconsciousness. Many of the influences triggering or inhibiting epileptic seizures produce alterations of vigilance or are produced by them. Nearly all chemical influences more or less cause diminution of vigilance. The enhancement of vigilance may inhibit seizures. Decreasing vigilance may act vice versa. As a means to enhance vigilance afferent stimuli are able to trigger seizures. This may be accomplished when singular or rhythmic stimulation of afferents gets the already excited neuronal system oscillating. This principle is also responsible for the strong correlation between triggering of seizures and the sleep/waking cycle with its different grades of neuronal synchronization. On the other hand, inhibition of seizures is possible by a continuously applied stimulation load, which may disturb the increasing excitatory oscillation. Also, conditioning may trigger or inhibit seizures. But the EEG biofeedback only is used to decrease abnormal neuronal activity.

  13. Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

    PubMed

    Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

    2015-12-01

    Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

    PubMed

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

    2015-03-15

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. Copyright © 2015 the American Physiological Society.

  15. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

    PubMed Central

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

    2015-01-01

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

  16. Distinct mechanisms underlie activation of hypothalamic neurosecretory neurons and their medullary catecholaminergic afferents in categorically different stress paradigms.

    PubMed Central

    Li, H Y; Ericsson, A; Sawchenko, P E

    1996-01-01

    Intermittent electrical footshock induces c-fos expression in parvocellular neurosecretory neurons expressing corticotropin-releasing factor and in other visceromotor cell types of the paraventricular hypothalamic nucleus (PVH). Since catecholaminergic neurons of the nucleus of the solitary tract and ventrolateral medulla make up the dominant loci of footshock-responsive cells that project to the PVH, these were evaluated as candidate afferent mediators of hypothalamic neuroendocrine responses. Rats bearing discrete unilateral transections of this projection system were exposed to a single 30-min footshock session and sacrificed 2 hr later. Despite depletion of the aminergic innervation on the ipsilateral side, shock-induced up-regulation of Fos protein and corticotropin-releasing factor mRNA were comparable in strength and distribution in the PVH on both sides of the brain. This lesion did, however, result in a substantial reduction of Fos expression in medullary aminergic neurons on the ipsilateral side. These results contrast diametrically with those obtained in a systemic cytokine (interleukin 1) challenge paradigm, where similar cuts ablated the Fos response in the ipsilateral PVH but left intact the induction seen in the ipsilateral medulla. We conclude that (i) footshock-induced activation of medullary aminergic neurons is a secondary consequence of stress, mediated via a descending projection transected by our ablation, (ii) stress-induced activation of medullary aminergic neurons is not necessarily predictive of an involvement of these cell groups in driving hypothalamic visceromotor responses to a given stressor, and (iii) despite striking similarities in the complement of hypothalamic effector neurons and their afferents that may be activated by stresses of different types, distinct mechanisms may underlie adaptive hypothalamic responses in each. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8637878

  17. How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse

    PubMed Central

    SUZUKI, Maasa; EBARA, Satomi; KOIKE, Taro; TONOMURA, Sotatsu; KUMAMOTO, Kenzo

    2012-01-01

    Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4–54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10–32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1–3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement. PMID:23229751

  18. How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse.

    PubMed

    Suzuki, Maasa; Ebara, Satomi; Koike, Taro; Tonomura, Sotatsu; Kumamoto, Kenzo

    2012-01-01

    Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4-54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10-32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1-3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement.

  19. Reciprocal synapses between outer hair cells and their afferent terminals: evidence for a local neural network in the mammalian cochlea.

    PubMed

    Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles

    2008-12-01

    Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

  20. Cerebellar afferents originating from the medullary reticular formation that are different from mossy, climbing or monoaminergic fibers in the rat.

    PubMed

    Luo, Yuanjun; Sugihara, Izumi

    2014-05-30

    Integration of cortical Purkinje cell inputs and brain stem inputs is essential in generating cerebellar outputs to the cerebellar nuclei (CN). Currently, collaterals of climbing and mossy fiber axons, noradrenergic, serotoninergic and cholinergic axons, and collaterals of rubrospinal axons are known to innervate the CN from the brain stem. We investigated whether other afferents to the CN from the medulla exist in the rat. Retrograde labeling revealed the presence of neurons that project to the CN but not to the cerebellar cortex in the median reticular formation in the rostrodorsal medulla (tentatively named 'caudal raphe interpositus area', CRI). Anterograde tracer injection into the CRI labeled abundant axonal terminals in the CN, mainly in the ventral parvocellular part of the posterior interposed and lateral nucleus. Axonal reconstruction showed that a single CRI axon projected to the CN with 170-1086 varicosities, more broadly and densely than collaterals of a mossy or climbing fiber axon. CRI axons had no or a few collaterals that projected to the granular and Purkinje cell layers of the cerebellar cortex with some small terminals, indicating that these axons are different from mossy fiber axons. CRI axons also had collaterals that projected to the medial vestibular nucleus and an ascending branch that was not reconstructed. The location of the CRI, electron microscopic observations, and immunostaining results all indicated that CRI axons are not monoaminergic. We conclude that CRI axons form a type of afferent projection to the CN that is different from mossy, climbing or monoaminergic fibers. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance

    PubMed Central

    Dempsey, Jerome A

    2012-01-01

    The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward ‘central command’ mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal ‘tonic’ activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O2 transport, increased central motor output and end-exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes – probably acting in concert with feedforward central command – contribute significantly to preserving O2 transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development. PMID:22826128

  2. New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance.

    PubMed

    Dempsey, Jerome A

    2012-09-01

    The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward 'central command' mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal 'tonic' activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O(2) transport, increased central motor output and end-exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes - probably acting in concert with feedforward central command - contribute significantly to preserving O(2) transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development.

  3. Dopaminergic Modulation of Cortical Plasticity in Alzheimer's Disease Patients

    PubMed Central

    Koch, Giacomo; Di Lorenzo, Francesco; Bonnì, Sonia; Giacobbe, Viola; Bozzali, Marco; Caltagirone, Carlo; Martorana, Alessandro

    2014-01-01

    In animal models of Alzheimer's disease (AD), mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) are impaired. In AD patients, LTP-like cortical plasticity is abolished, whereas LTD seems to be preserved. Dopaminergic transmission has been hypothesized as a new player in ruling mechanisms of cortical plasticity in AD. We aimed at investigating whether administration of the dopamine agonist rotigotine (RTG) could modulate cortical plasticity in AD patients, as measured by theta burst stimulation (TBS) protocols of repetitive transcranial stimulation applied over the primary motor cortex. Thirty mild AD patients were tested in three different groups before and after 4 weeks of treatment with RTG, rivastigmine (RVT), or placebo (PLC). Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS protocols. Short-latency afferent inhibition (SAI) protocol was performed to indirectly assess central cholinergic activity. A group of age-matched healthy controls was recruited for baseline comparisons. Results showed that at baseline, AD patients were characterized by impaired LTP-like cortical plasticity, as assessed by iTBS. These reduced levels of LTP-like cortical plasticity were increased and normalized after RTG administration. No effect was induced by RVT or PLC on LTP. LTD-like cortical plasticity was not modulated in any condition. Cholinergic activity was increased by both RTG and RVT. Our findings reveal that dopamine agonists may restore the altered mechanisms of LTP-like cortical plasticity in AD patients, thus providing novel implications for therapies based on dopaminergic stimulation. PMID:24859851

  4. Color threshold and ratio of S100 beta, MAP5, NF68/200, GABA & GAD. I. Distribution in inner ear afferents

    NASA Technical Reports Server (NTRS)

    Fermin, C. D.; Martin, D. S.; Hara, H.

    1997-01-01

    Afferents of chick embryos (Gallus domesticus) VIIIth nerve were examined at E3, E6, E9, E13, El7, and hatching (NH) for anti-S100 beta, anti-MAP5, anti-GABA, anti-GAD and anti-NF68/200 stain. Different ages were processed together to determine if the distribution of these antibodies changed during synaptogenesis and myelination. Color thresholding showed that saturation of pixels changed for S100 beta only 5%, for NF68/200 10%, and for MAP5, 10%, between E9-NH. Color ratio of NF68/200 over MAP5 was 1.00 at E13 and 0.25 at E16 and NH. S100 beta, GABA and GAD were co-expressed on nerve endings at the edge of the maculae and center of the cristae, whereas hair cells in the center of the maculae expressed either S100 beta or GABA, but not both. S100 beta/NF68/200 shared antigenic sites on the chalices, but NF68/200 expression was higher than S100 beta in the chalices at hatching. MAP5 was expressed in more neurons than NF68/200 at E11, whereas NF68/200 was more abundant than MAP5 at hatching. The results suggest that: 1) the immunoexpression of these neuronal proteins is modulated concomitantly with the establishment of afferent synapses and myelination; 2) S100 beta may serve a neurotrophic function in the chalices where it is co-expressed with the neurotransmitter GABA and its synthesizing enzyme GAD.

  5. Central projections of antennular chemosensory and mechanosensory afferents in the brain of the terrestrial hermit crab (Coenobita clypeatus; Coenobitidae, Anomura)

    PubMed Central

    Tuchina, Oksana; Koczan, Stefan; Harzsch, Steffen; Rybak, Jürgen; Wolff, Gabriella; Strausfeld, Nicholas J.; Hansson, Bill S.

    2015-01-01

    The Coenobitidae (Decapoda, Anomura, Paguroidea) is a taxon of hermit crabs that includes two genera with a fully terrestrial life style as adults. Previous studies have shown that Coenobitidae have evolved a sense of spatial odor localization that is behaviorally highly relevant. Here, we examined the central olfactory pathway of these animals by analyzing central projections of the antennular nerve of Coenobita clypeatus, combining backfilling of the nerve with dextran-coupled dye, Golgi impregnations and three-dimensional reconstruction of the primary olfactory center, the antennular lobe. The principal pattern of putative olfactory sensory afferents in C. clypeatus is in many aspects similar to what have been established for aquatic decapod crustaceans, such as the spiny lobster Panulirus argus. However, there are also obvious differences that may, or may not represent adaptations related to a terrestrial lifestyle. In C. clypeatus, the antennular lobe dominates the deutocerebrum, having more than one thousand allantoid-shaped subunits. We observed two distinct patterns of sensory neuron innervation: putative olfactory afferents from the aesthetascs either supply the cap/subcap region of the subunits or they extend through its full depth. Our data also demonstrate that any one sensory axon can supply input to several subunits. Putative chemosensory (non-aesthetasc) and mechanosensory axons represent a different pathway and innervate the lateral and median antennular neuropils. Hence, we suggest that the chemosensory input in C. clypeatus might be represented via a dual pathway: aesthetascs target the antennular lobe, and bimodal sensilla target the lateral antennular neuropil and median antennular neuropil. The present data is compared to related findings in other decapod crustaceans. PMID:26236202

  6. [Research of clinic and laboratory of face acupuncture effect and the exploration of their afferent pathways].

    PubMed

    Zhang, S; Tang, Z; Wu, Z; Li, L; Zhang, R

    1996-01-01

    This paper shows that face acupuncture point (Liver point through gallbladder point) has significant effect of promoting bile secretion on the patients of cholecystectomy and choledochotomy and drainage. Special different point is that face acupuncture stimulation has very obvious posteffect comparing with other three body acupuncture groups and this posteffect lasts more than fifty minuts. The results also show that the successful rate of face acupuncture anesthesia is better than body acupuncture anesthesia during the ligation of oviduct and subtotal gastrectomy. The above results are all analysed statistically and there is a very significant difference among them. During the research on domestic dog anesthesiaed by face acupuncture, the successful rate is 86.5%, moreover the analgesic effect of face acupuncture can be blocked by blocking bilateral postganglionic fibre of trigeminal ganglion with 2% procaine. The results imply that trigeminal ganglion is the main afferent way of stimulation information of face acupuncture.

  7. Botulinum Toxin Injections Reduce Associative Plasticity in Patients with Primary Dystonia

    PubMed Central

    Kojovic, Maja; Caronni, Antonio; Bologna, Matteo; Rothwell, John C.; Bhatia, Kailash P.; Edwards, Mark J.

    2014-01-01

    Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long-term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation-evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short-interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. PMID:21469207

  8. Trigemino-gustatory interactions: a randomized controlled clinical trial assessing the effects of selective anesthesia of dental afferents on taste thresholds.

    PubMed

    Lecor, Papa Abdou; Touré, Babacar; Boucher, Yves

    2018-03-01

    This study aimed at analyzing the effect of the temporary removal of trigeminal dental afferents on electrogustometric thresholds (EGMt). EGMt were measured in 300 healthy subjects randomized in three groups, in nine loci on the right and left side (RS, LS) of the tongue surface before and after anesthesia. Group IAN (n = 56 RS, n = 44 LS) received intraosseous local anesthesia of the inferior alveolar nerve (IAN). Group MdN received mandibular nerve (MdN) block targeting IAN before its entrance into the mandibular foramen (n = 60, RS, and n = 40, LS); group MxN receiving maxillary nerve (MxN) anesthesia (n = 56 RS and n = 44 LS) was the control group. Differences between mean EGMt were analyzed with the Wilcoxon test; correlation between type of anesthesia and EGMt was performed with Spearman's rho, all with a level of significance set at p ≤ 0.05. Significant EGMt (μA) differences before and after anesthesia were found in all loci with MdN and IAN on the ipsilateral side (p < 0.05), but not with MxN. Anesthesia of the MdN was positively correlated with the increase in EGMt (p < 0.001). Selective anesthesia of IAN was positively correlated only with the increase in EGMt measured at posterior and dorsal loci of the tongue surface (p < 0.01). The increase in EGMt following IAN anesthesia suggests a participation of dental afferents in taste perception. Extraction of teeth may impair food intake not only due to impaired masticatory ability but also to alteration of neurological trigemino-gustatory interactions. PACTR201602001452260.

  9. Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

    PubMed Central

    Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

    2014-01-01

    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

  10. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

    PubMed Central

    Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

    2016-01-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

  11. Amyloid-β expression in retrosplenial cortex of 3xTg-AD mice: relationship to cholinergic axonal afferents from medial septum

    PubMed Central

    Robertson, Richard T.; Baratta, Janie; Yu, Jen; LaFerla, Frank M.

    2009-01-01

    Triple transgenic (3xTg-AD) mice harboring the presenilin 1, amyloid precursor protein, and tau transgenes (Oddo et al., 2003) display prominent levels of amyloid-beta (Aβ) immunoreactivity in forebrain regions. The Aβ immunoreactivity is first seen intracellularly in neurons and later as extracellular plaque deposits. The present study examined Aβ immunoreactivity that occurs in layer III of the granular division of retrosplenial cortex (RSg). This pattern of Aβ immunoreactivity in layer III of RSg develops relatively late, and is seen in animals older than 14 mo. The appearance of the Aβ immunoreactivity is similar to an axonal terminal field and thus may offer a unique opportunity to study the relationship between afferent projections and the formation of Aβ deposits. Axonal tract tracing techniques demonstrated that the pattern of axon terminal labeling in layer III of RSg, following placement of DiI in medial septum, is remarkably similar to the pattern of cholinergic axons in RSg, as detected by acetylcholinesterase histochemical staining, choline acetyltransferase immunoreactivity, or p75 receptor immunoreactivity; this pattern also is strikingly similar to the band of Aβ immunoreactivity. In animals sustaining early damage to the medial septal nucleus (prior to the advent of Aβ immunoreactivity), the band of Aβ in layer III of RSg does not develop; the corresponding band of cholinergic markers also is eliminated. In older animals (after the appearance of the Aβ immunoreactivity) damage to cholinergic afferents by electrolytic lesions, immunotoxin lesions, or cutting the cingulate bundle, result in a rapid loss of the cholinergic markers and a slower reduction of Aβ immunoreactivity. These results suggest that the septal cholinergic axonal projections transport Aβ or APP to layer III of RSg. PMID:19772895

  12. Balanced excitation and inhibition are required for high-capacity, noise-robust neuronal selectivity

    PubMed Central

    Abbott, L. F.; Sompolinsky, Haim

    2017-01-01

    Neurons and networks in the cerebral cortex must operate reliably despite multiple sources of noise. To evaluate the impact of both input and output noise, we determine the robustness of single-neuron stimulus selective responses, as well as the robustness of attractor states of networks of neurons performing memory tasks. We find that robustness to output noise requires synaptic connections to be in a balanced regime in which excitation and inhibition are strong and largely cancel each other. We evaluate the conditions required for this regime to exist and determine the properties of networks operating within it. A plausible synaptic plasticity rule for learning that balances weight configurations is presented. Our theory predicts an optimal ratio of the number of excitatory and inhibitory synapses for maximizing the encoding capacity of balanced networks for given statistics of afferent activations. Previous work has shown that balanced networks amplify spatiotemporal variability and account for observed asynchronous irregular states. Here we present a distinct type of balanced network that amplifies small changes in the impinging signals and emerges automatically from learning to perform neuronal and network functions robustly. PMID:29042519

  13. Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

    PubMed

    Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen; Tjen-A-Looi, Stephanie C; Longhurst, John C

    2018-05-01

    We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C 7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the

  14. Effects of long-term bed rest on H-reflex and motor evoked potential in lower leg muscles during standing.

    PubMed

    Yamanaka, K; Yamamoto, S; Nakazawa, K; Yano, H; Suzuki, Y; Fukunaga, T

    1999-07-01

    Maximal H-reflex amplitude (Hmax) compared with maximal M-response (Mmax) has been generally used to assess the efficacy of the monosynaptic transmission from Ia afferents to alpha motoneurons in spinal cord. In previous studies, it has been demonstrated that H-reflex in soleus muscle (SOL) is inhibited during free standing due to an increase in presynaptic inhibition of the Ia afferent terminals to SOL motoneurones (Katz et al. 1988, Koceja et al. 1993). Transcranial magnetic stimulation (TMS) of human motor cortex excites the corticospinal system monosynapticaly connecting to spinal alpha motoneurones. However, it is not clear whether or not the motor evoked potentials (MEPs) in SOL and tibialis anterior (TA) muscles induced by TMS are modulated during standing (Ackermann et al. 1991, Lavoie et al. 1995). Considering that postural control functions change with exposure to weightlessness, we supposed that the excitability of SOL and TA spinal motoneurons from Ia afferents and/or corticospinal tracts during free standing would change after long-term bed rest (BR). The aim of this study was to investigate the effect of BR on H-reflex and MEP in SOL and TA during free standing.

  15. Effects of high pressure processing on activity and structure of soluble acid invertase in mango pulp, crude extract, purified form and model systems.

    PubMed

    Li, Renjie; Wang, Yongtao; Ling, Jiangang; Liao, Xiaojun

    2017-09-15

    The effects of high pressure processing (HPP) on the activity of soluble acid invertase (SAI) in mango pulp, crude extract, purified SAI and purified SAI in model systems (pectin, bovine serum albumin (BSA), sugars and pH 3-7) were investigated. The activity of SAI in mango pulp was increased after HPP, and that in crude extract stayed unchanged. The activity of purified SAI was decreased after HPP at 45 and 50°C. Pectin exhibited a concentration-dependent protection for purified SAI against HPP at 50°C/600MPa for 30min. Pectin that had an esterification degree (DE) of 85% exhibited a greater protection than pectin that had a DE of 20-34%. BSA, acidic pH (3-6) and sucrose also exhibited protection for purified SAI against HPP. HPP at 50°C/600MPa for 30min disrupted the secondary structure and tertiary structure of purified SAI, but no aggregation of purified SAI was observed after HPP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. On a method to detect long-latency excitations and inhibitions of single hand muscle motoneurons in man.

    PubMed

    Awiszus, F; Feistner, H; Schäfer, S S

    1991-01-01

    The peri-stimulus-time histogram (PSTH) analysis of stimulus-related neuronal spike train data is usually regarded as a method to detect stimulus-induced excitations or inhibitions. However, for a fairly regularly discharging neuron such as the human alpha-motoneuron, long-latency modulations of a PSTH are difficult to interpret as PSTH modulations can also occur as a consequence of a modulated neuronal autocorrelation. The experiments reported here were made (i) to investigate the extent to which a PSTH of a human hand-muscle motoneuron may be contaminated by features of the autocorrelation and (ii) to develop methods that display the motoneuronal excitations and inhibitions without such contamination. Responses of 29 single motor units to electrical ulnar nerve stimulation below motor threshold were investigated in the first dorsal interosseous muscle of three healthy volunteers using an experimental protocol capable of demonstrating the presence of autocorrelative modulations in the neuronal response. It was found for all units that the PSTH as well as the cumulative sum (CUSUM) derived from these responses were severely affected by the presence of autocorrelative features. On the other hand, calculating the CUSUM in a slightly modified form yielded--for all units investigated--a neuronal output feature sensitive only to motoneuronal excitations and inhibitions induced by the afferent volley. The price that has to be paid to arrive at such a modified CUSUM (mCUSUM) was a high computational effort prohibiting the on-line availability of this output feature during the experiment. It was found, however, that an interspike interval superposition plot (IISP)--easily obtainable during the experiment--is also free of autocorrelative features.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Neural tuning characteristics of auditory primary afferents in the chicken embryo.

    PubMed

    Jones, S M; Jones, T A

    1995-02-01

    Primary afferent activity was recorded from the cochlear ganglion in chicken embryos (Gallus domesticus) at 19 days of incubation (E19). The ganglion was accessed via the recessus scala tympani and impaled with glass micropipettes. Frequency tuning curves were obtained using a computerized threshold tracking procedure. Tuning curves were evaluated to determine characteristics frequencies (CFs), CF thresholds, slopes of low and high frequency flanks, and tip sharpness (Q10dB). The majority of tuning curves exhibited the typical 'V' shape described for older birds and, on average, appeared relatively mature based on mean values for CF thresholds (59.6 +/- 20.3 dBSPL) and tip sharpness (Q10dB = 5.2 +/- 3). The mean slopes of low (61.9 +/- 37 dB/octave) and high (64.6 +/- 33 dB/octave) frequency flanks although comparable were somewhat less than those reported for 21-day-old chickens. Approximately 14% of the tuning curves displayed an unusual 'saw-tooth' pattern. CFs ranged from 188 to 1623 Hz. The highest CF was well below those reported for post-hatch birds. In addition, a broader range of Q10dB values (1.2 to 16.9) may related to a greater variability in embryonic tuning curves. Overall, these data suggest that an impressive functional maturity exists in the embryo at E19. The most significant sign of immaturity was the limited expression of high frequencies. It is argued that the limited high CF in part may be due to the developing middle ear transfer function and/or to a functionally immature cochlear base.

  18. Neural tuning characteristics of auditory primary afferents in the chicken embryo

    NASA Technical Reports Server (NTRS)

    Jones, S. M.; Jones, T. A.

    1995-01-01

    Primary afferent activity was recorded from the cochlear ganglion in chicken embryos (Gallus domesticus) at 19 days of incubation (E19). The ganglion was accessed via the recessus scala tympani and impaled with glass micropipettes. Frequency tuning curves were obtained using a computerized threshold tracking procedure. Tuning curves were evaluated to determine characteristics frequencies (CFs), CF thresholds, slopes of low and high frequency flanks, and tip sharpness (Q10dB). The majority of tuning curves exhibited the typical 'V' shape described for older birds and, on average, appeared relatively mature based on mean values for CF thresholds (59.6 +/- 20.3 dBSPL) and tip sharpness (Q10dB = 5.2 +/- 3). The mean slopes of low (61.9 +/- 37 dB/octave) and high (64.6 +/- 33 dB/octave) frequency flanks although comparable were somewhat less than those reported for 21-day-old chickens. Approximately 14% of the tuning curves displayed an unusual 'saw-tooth' pattern. CFs ranged from 188 to 1623 Hz. The highest CF was well below those reported for post-hatch birds. In addition, a broader range of Q10dB values (1.2 to 16.9) may related to a greater variability in embryonic tuning curves. Overall, these data suggest that an impressive functional maturity exists in the embryo at E19. The most significant sign of immaturity was the limited expression of high frequencies. It is argued that the limited high CF in part may be due to the developing middle ear transfer function and/or to a functionally immature cochlear base.

  19. Pulmonary stretch receptor afferents activate excitatory amino acid receptors in the nucleus tractus solitarii in rats.

    PubMed

    Bonham, A C; Coles, S K; McCrimmon, D R

    1993-05-01

    1. The goal of the present study was to identify potential neurotransmitter candidates in the Breuer-Hering (BH) reflex pathway, specifically at synapses between the primary afferents and probable second-order neurones (pump cells) within the nucleus tractus solitarii (NTS). We hypothesized that if activation of specific receptors in the NTS is required for production of the BH reflex, then (1) injection of the receptor agonist(s) would mimic the reflex response (apnoea), (2) injection of appropriate antagonists would impair the apnoea produced by either lung inflation or agonist injection, and (3) second-order neurones in the pathway would be excited by either lung inflation or agonists while antagonists would prevent the response to either. 2. Studies were carried out either in spontaneously breathing or in paralysed, thoracotomized and ventilated rats in which either diaphragm EMG or phrenic nerve activity, expired CO2 concentration and arterial pressure were continuously monitored. The BH reflex was physiologically activated by inflating the lungs. 3. Pressure injections (0.03-15 pmol) of selective excitatory amino acid (EAA) receptor agonists, quisqualic acid (Quis) and N-methyl-D-aspartic acid (NMDA) into an area of the NTS shown previously to contain neurones required for production of the BH reflex produced dose-dependent apnoeas that mimicked the response to lung inflation. Injection of substance P (0.03-4 pmol) did not alter baseline respiratory pattern. 4. Injections of the EAA antagonists, kynurenic acid (Kyn; 0.6-240 pmol), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the BH region of the NTS reversibly impaired the apnoea produced by lung inflation. All three antagonists reduced or abolished the apnoeas resulting from injection of Quis or NMDA, and slowed baseline respiratory frequency. In contrast, injections of the highly selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acids (AP5), in

  20. Involvement of metabotropic glutamate 5 receptor in visceral pain.

    PubMed

    Lindström, Erik; Brusberg, Mikael; Hughes, Patrick A; Martin, Christopher M; Brierley, Stuart M; Phillis, Benjamin D; Martinsson, Rakel; Abrahamsson, Christina; Larsson, Håkan; Martinez, Vicente; Blackshaw, L Ashley

    2008-07-15

    Metabotropic glutamate 5 receptor (mGluR5) antagonists are effective in animal models of inflammatory and neuropathic pain. The involvement of mGluR5 in visceral pain pathways from the gastrointestinal tract is as yet unknown. We evaluated effects of mGluR5 antagonists on the colorectal distension (CRD)-evoked visceromotor (VMR) and cardiovascular responses in conscious rats, and on mechanosensory responses of mouse colorectal afferents in vitro. Sprague-Dawley rats were subjected to repeated, isobaric CRD (12 x 80 mmHg, for 30s with 5 min intervals). The VMR and cardiovascular responses to CRD were monitored. The mGluR5 antagonists MPEP (1-10 micromol/kg, i.v.) and MTEP (1-3 micromol/kg, i.v.) reduced the VMR to CRD dose-dependently with maximal inhibition of 52+/-8% (p<0.01) and 25+/-11% (p<0.05), respectively, without affecting colonic compliance. MPEP (10 micromol/kg, i.v.) reduced CRD-evoked increases in blood pressure and heart rate by 33+/-9% (p<0.01) and 35+/-8% (p<0.05), respectively. Single afferent recordings were made from mouse pelvic and splanchnic nerves of colorectal mechanoreceptors. Circumferential stretch (0-5 g force) elicited slowly-adapting excitation of action potentials in pelvic distension-sensitive afferents. This response was reduced 55-78% by 10 microM MTEP (p<0.05). Colonic probing (2g von Frey hair) activated serosal splanchnic afferents; their responses were reduced 50% by 10 microM MTEP (p<0.01). We conclude that mGluR5 antagonists inhibit CRD-evoked VMR and cardiovascular changes in conscious rats, through an effect, at least in part, at peripheral afferent endings. Thus, mGluR5 participates in mediating mechanically evoked visceral nociception in the gastrointestinal tract.

  1. Inhibitory effects of silodosin on the bladder mechanosensitive afferent activities and their relation with bladder myogenic contractions in male rats with bladder outlet obstruction.

    PubMed

    Aizawa, Naoki; Watanabe, Daiji; Fukuhara, Hiroshi; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio; Igawa, Yasuhiko

    2018-03-06

    We investigated the effects of silodosin, an α1A-adrenoceptor (AR) antagonist, on bladder function, especially on non-voiding contractions (NVCs), in a male rat model of bladder outlet obstruction (BOO) by evaluating cystometry (CMG) findings and bladder mechanosensitive single-unit afferent activities (SAAs), related with microcontractions, which may be similar with NVCs and to be of myogenic origin, in the rat model. BOO was created by partial ligation of the posterior urethra. At 4 days after surgery for BOO, an osmotic pump filled with silodosin (0.12 mg/kg/day) or its vehicle was subcutaneously implanted. At 10 days after surgery, CMG and SAAs measurements were taken under conscious and urethane-anesthetized conditions, respectively. The SAAs of Aδ- and C-fibers, which were identified by electrical stimulation of the pelvic nerve and by bladder distention, and intravesical pressure were recorded during constant bladder-filling with saline. Microcontractions were divided into three phases: "ascending," "descending," and "stationary." The silodosin-treated group showed a smaller number of NVCs in CMG measurements and lower SAAs of both Aδ- and C-fibers than the vehicle-treated group during bladder-filling. Moreover, in the vehicle-treated groups, the SAAs of both fibers for the ascending phase of microcontractions were significantly higher than those for the other two phases. On the contrary, no significant change was found between any of these three phases in the silodosin-treated group. The present results suggest that silodosin inhibits the SAAs of mechanosensitive Aδ- and C-fibers at least partly due to suppressing myogenic bladder contractions in male BOO rats. © 2018 Wiley Periodicals, Inc.

  2. Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

    PubMed Central

    Churyukanov, Maxim; Plaghki, Léon; Legrain, Valéry; Mouraux, André

    2012-01-01

    Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively. PMID:22558230

  3. Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

    PubMed

    Atkinson, M E; Shehab, S A

    1986-12-01

    In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

  4. Proprioceptive encoding of head position in the black soldier fly, Hermetia illucens (L.) (Stratiomyidae).

    PubMed

    Paulk, Angelique; Gilbert, Cole

    2006-10-01

    Because the eyes of insects cannot be moved independently of the head, information about head posture is essential for stabilizing the visual world or providing information about the direction of gaze. We examined the external anatomy and physiological capabilities of a head posture proprioceptor, the prosternal organ (PO), located at the base of the neck in the black soldier fly, Hermetia illucens (L.) (Family: Stratiomyidae). The PO is sexually isomorphic and is composed of two fused plates of about 130 mechanosensory hairs set in asymmetrical sockets whose orientation varies across the organ. A multi-joint mechanical coupling between the head, neck membrane, and contact sclerites deflects the hairs more or less to increase or decrease their level of excitation. The PO sensory afferents project to the central nervous system (CNS) via a pair of bilateral prosternal nerves (PN) to the fused thoracic ganglia. Simultaneous recording of spiking activity in the PN and videotaping of wind-induced and voluntary head movements around all three axes of head rotation reveal that a few PN afferents are active at rest, but activity increases tonically in response to head deflections. Activity is significantly modulated by change in head angles around the pitch (+/-40 degrees ), yaw (+/-30 degrees ) and roll (more than +/-90 degrees ) axes, although the dynamic range of spiking activity differs for each axis of rotation. Prosternal nerve afferents are bilaterally excited (inhibited) by pitch down (up); excited (inhibited) by head yaw toward the ipsilateral (contralateral) side; excited by roll down toward the ipsilateral side, but little inhibited by roll toward the opposite side. Although bilateral comparison of activity in PN afferents reliably encodes head posture around a given rotational axis, from the point of view of the CNS, the problem of encoding head posture is ill-posed with three axes of rotation and only two streams of afferent information. Furthermore, when the

  5. Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in squirrel monkey vestibular nuclei. III. Correlation with vestibulospinal and vestibuloocular output pathways

    NASA Technical Reports Server (NTRS)

    Boyle, R.; Goldberg, J. M.; Highstein, S. M.

    1992-01-01

    1. A previous study measured the relative contributions made by regularly and irregularly discharging afferents to the monosynaptic vestibular nerve (Vi) input of individual secondary neurons located in and around the superior vestibular nucleus of barbiturate-anesthetized squirrel monkeys. Here, the analysis is extended to more caudal regions of the vestibular nuclei, which are a major source of both vestibuloocular and vestibulospinal pathways. As in the previous study, antidromic stimulation techniques are used to classify secondary neurons as oculomotor or spinal projecting. In addition, spinal-projecting neurons are distinguished by their descending pathways, their termination levels in the spinal cord, and their collateral projections to the IIIrd nucleus. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from secondary neurons as shocks of increasing strength were applied to Vi. Shocks were normalized in terms of the threshold (T) required to evoke field potentials in the vestibular nuclei. As shown previously, the relative contribution of irregular afferents to the total monosynaptic Vi input of each secondary neuron can be expressed as a %I index, the ratio (x100) of the relative sizes of the EPSPs evoked by shocks of 4 x T and 16 x T. 3. Antidromic stimulation was used to type secondary neurons as 1) medial vestibulospinal tract (MVST) cells projecting to spinal segments C1 or C6; 2) lateral vestibulospinal tract (LVST) cells projecting to C1, C6; or L1; 3) vestibulooculo-collic (VOC) cells projecting both to the IIIrd nucleus and by way of the MVST to C1 or C6; and 4) vestibuloocular (VOR) neurons projecting to the IIIrd nucleus but not to the spinal cord. Most of the neurons were located in the lateral vestibular nucleus (LV), including its dorsal (dLV) and ventral (vLV) divisions, and adjacent parts of the medial (MV) and descending nuclei (DV). Cells receiving quite different proportions of their direct inputs

  6. Afferent Drive Elicits Ongoing Pain in a Model of Advanced Osteoarthritis

    PubMed Central

    Okun, Alec; Liu, Ping; Davis, Peg; Ren, Jiyang; Remeniuk, Bethany; Brion, Triza; Ossipov, Michael H.; Xie, Jennifer; Dussor, Gregory O.; King, Tamara; Porreca, Frank

    2012-01-01

    Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience pain at rest (i.e., ongoing pain)that is generally resistant to non-steroidal anti-inflammatory drugs (NSAIDs). Injection of monosodium iodoacetate (MIA) into the intra-articular space of the rodent knee is a well-established model of OA that elicits weight-bearing asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain is present in this model is unknown. Additionally, the possible relationship of ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg). However, only rats treated with the highest dose of MIA showed conditioned place preference to a context paired with intra-articular lidocaine, indicating relief from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed to block MIA-induced ongoing pain. Systemic AMG9810, a TRPV1 antagonist, effectively blocked thermal hypersensitivity, but failed to block high dose MIA-induced weight asymmetry or ongoing pain. Additionally, systemic or intra-articular HC030031, a TRPA1 antagonist, failed to block high dose MIA-induced weight asymmetry or ongoing pain. Our studies suggest that a high dose of intra-articular MIA induces ongoing pain originating from the site of injury that is dependent on afferent fiber activity but apparently independent of TRPV1 or TRPA1 activation. Identification of mechanisms driving ongoing pain may enable development of improved treatments for patients with severe OA pain and diminish the need for joint replacement surgery. PMID:22387095

  7. Afferent and efferent connections of the mesencephalic reticular formation in goldfish.

    PubMed

    Luque, M A; Pérez-Pérez, M P; Herrero, L; Torres, B

    2008-03-18

    The physiology of the mesencephalic reticular formation (MRF) in goldfish suggests its contribution to eye and body movements, but the afferent and efferent connections underlying such movements have not been determined. Therefore, we injected the bidirectional tracer biotinylated dextran amine into functionally identified MRF sites. We found retrogradely labelled neurons and anterogradely labelled boutons within nuclei of the following brain regions: (1) the telencephalon: a weak and reciprocal connectivity was confined to the central zone of area dorsalis and ventral nucleus of area ventralis; (2) the diencephalon: reciprocal connections were abundant in the ventral and dorsal thalamic nuclei; the central pretectal nucleus was also reciprocally wired with the MRF, but only boutons were present in the superficial pretectal nucleus; the preoptic and suprachiasmatic nuclei showed abundant neurons and boutons; the MRF was reciprocally connected with the preglomerular complex and the anterior tuberal nucleus; (3) the mesencephalon: neurons and boutons were abundant within deep tectal layers; reciprocal connections were also present within the torus semicircularis and the contralateral MRF; neurons were abundant within the nucleus isthmi; and (4) the rhombencephalon: the superior and middle parts of the reticular formation received strong projections from the MRF, while the projection to the inferior area was weaker; sparse neurons were present throughout the reticular formation; a reciprocal connectivity was observed with the sensory trigeminal nucleus; the medial and magnocellular nuclei of the octaval column projected to the MRF. These results support the participation of the MRF in the orienting response. The MRF could also be involved in other motor tasks triggered by visual, auditory, vestibular, or somatosensory signals.

  8. Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

    PubMed

    Kurachi, M; Aihara, H

    1984-09-01

    The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

  9. Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

    2011-10-01

    The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

  10. The role in masseter muscle activities of functionally elicited periodontal afferents from abutment teeth under overdentures.

    PubMed

    Mushimoto, E

    1981-09-01

    Five overdenture wearers with a small number of remaining natural teeth were selected to evaluate the effect of the afferent input from periodontal mechanoreceptors on masseter activity in man. As a control, a full denture wearer was included. The subjects were instructed to chew a piece of gum, and/or tap their teeth. Surface EmG from the bilateral masseter muscles were recorded and analysed. When functional pressure was applied, during chewing, to the abutment teeth as well as to mucosa through the denture base, masseter activities were encouraged. Following application of anaesthesia to the periodontal membrane of the abutments, masseter activities were reduced. The duration of the silent period (SP) appearing in the EMG burst following tooth tapping was significantly increased with root support compared to mucosal support only. With topical anaesthesia of the periodontal tissues, SP duration decreased significantly. In conclusion, it has become apparent that the pressure sensibility of abutment teeth bearing functional pressure under an overdenture base is capable of facilitating masseter activity, as one of the sources of oral sensory input during mastication.

  11. The rostromedial tegmental nucleus (RMTg), a major GABAergic afferent to midbrain dopamine neurons, selectively encodes aversive stimuli and promotes behavioral inhibition

    PubMed Central

    Jhou, Thomas C.; Fields, Howard L.; Baxter, Mark G.; Saper, Clifford B.; Holland, Peter C.

    2009-01-01

    Summary Separate studies have implicated the lateral habenula (LHb) or amygdala-related regions in processing aversive stimuli, but their relationships to each other and to appetitive motivational systems are poorly understood. We show that neurons in the recently identified GABAergic rostromedial tegmental nucleus (RMTg), which receive a major LHb input, project heavily to midbrain dopamine neurons, and show phasic activations and/or Fos induction after aversive stimuli (footshocks, shock-predictive cues, food deprivation, or reward omission) and inhibitions after rewards or reward-predictive stimuli. RMTg lesions markedly reduce passive fear behaviors (freezing, open-arm avoidance) dependent on the extended amygdala, periaqueductal gray, or septum, all regions that project directly to the RMTg. In contrast, RMTg lesions spare or enhance active fear responses (treading, escape) in these same paradigms. These findings suggest that aversive inputs from widespread brain regions and stimulus modalities converge onto the RMTg, which opposes reward and motor-activating functions of midbrain dopamine neurons PMID:19285474

  12. Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs.

    PubMed

    Coleridge, H M; Coleridge, J C

    1977-04-01

    We recorded impulses from afferent vagal C-fibres (conduction velocities 0.8-2.4 m/sec) arising from endings in the lungs of anesthetized dogs with open chest. Endings were of two types ('pulmonary' and 'bronchial') distinguished by their response and accessibility to capsaicin and phenyl diguanide injected into the right or left atrium. 'Pulmonary' endings, stimulated only by capsaicin and accessible through the pulmonary circulation, have been described previously. 'Bronchial' endings were stimulated by both capsicin and phenyl diguanide and were accessible through the bronchial circulation. Eight of 28 'bronchial' endings were located in large airways within 4 cm of the hilum, and two were in small airways near the edge of the lung. The precise location of the remaining 'bronchial' endings was not determined but we think that many were in the airways. 'Bronchial' endings had a sparse and irregular spontaneous discharge. They were stimulated by the inhalation of 5% histamine aerosol, the evoked discharge having no obvious relation to the phase of ventilation. A few were weakly stimulated by hyperinflating the lungs; deflation was without effect. The function of these endings is unknown.

  13. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

    NASA Astrophysics Data System (ADS)

    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  14. St. John’s Wort enhances the synaptic activity of the nucleus of the solitary tract

    PubMed Central

    Vance, Katie M.; Ribnicky, David M.; Hermann, Gerlinda E.; Rogers, Richard C.

    2014-01-01

    Objective St. John’s Wort extract, which is commonly used to treat depression, inhibits the reuptake of several neurotransmitters, including glutamate, serotonin, norepinephrine, and dopamine. Glutamatergic visceral vagal afferents synapse upon neurons of the solitary tract (NST); thus, we evaluated whether St. John’s Wort extract modulates glutamatergic neurotransmission within the NST. Materials and Methods We used live cell calcium imaging to evaluate whether St. John’s Wort and its isolated components hypericin and hyperforin increase the excitability of pre-labeled vagal afferent terminals synapsing upon the NST. We used voltage-clamp recordings of spontaneous miniature excitatory postsynaptic currents (mEPSCs) to evaluate whether St. John’s Wort alters glutamate release from vagal afferents onto NST neurons. Results Our imaging data show that St. John’s Wort (50 μg/mL) increased the intracellular calcium levels of stimulated vagal afferent terminals compared to the bath control. This increase in presynaptic vagal afferent calcium by the extract coincides with an increase in neurotransmitter release within the nucleus of the solitary tract, as the frequency of mEPSCs is significantly higher in the presence of the extract compared to the control. Finally, our imaging data show that hyperforin, a known component of St. John’s Wort extract, also significantly increases terminal calcium levels. Conclusion These data suggest that St. John’s Wort extract can significantly increase the probability of glutamate release from vagal afferents onto the NST by increasing presynaptic calcium. The in vitro vagal afferent synapse with NST neurons is an ideal model system to examine the mechanism of action of botanical agents on glutamatergic neurotransmission. PMID:24985104

  15. Meteorological conditions at the Caucasus Observatory of the SAI MSU from the results of the 2007-2015 campaign

    NASA Astrophysics Data System (ADS)

    Kornilov, V. G.; Kornilov, M. V.; Shatsky, N. I.; Vozyakova, O. V.; Gorbunov, I. A.; Safonov, B. S.; Potanin, S. A.; Cheryasov, D. V.; Senik, V. A.

    2016-09-01

    Based on the measurements performed from 2007 to 2015 at the summit of Mount Shatdzhatmaz adjacent to the 2.5-m telescope at the Caucasus Observatory of the SAI MSU, we have determined the statistical characteristics of basic meteorological parameters: the ambient air temperature, the ground wind speed, and the relative humidity. The stability of these parameters over the entire period of our measurements and their variations within an annual cycle have been studied. The median temperature on clear nights is +3.2°C, although there are nights with a temperature below -15°C. The typical ground wind speed is 3 m s-1; the probability of a wind stronger than 10 m s-1 does not exceed 2%. The losses of observing time due to high humidity are maximal in the summer period but, on the whole, are small over a year, less than 10%. We have estimated the absolute water vapor content in the atmosphere, which is especially important for infrared observations. Minimum precipitablewater vapor is observed in December-February; the median value over these months is 5 mm. We additionally provide the wind speeds at various altitudes above the ground (from 1 to 16 km) that we obtained when measuring the optical turbulence. We present the results and technique of our measurements of the annual amount of clear night astronomical time, which is, on average, 1320 h, i.e., 45% of the possible one at the latitude of the observatory. The period from mid-September to mid-March accounts for about 70% of the clear time. A maximum of clear skies is observed in November, when its fraction reaches 60% of the possible astronomical night time.

  16. Nociceptive Afferent Activity Alters the SI RA Neuron Response to Mechanical Skin Stimulation

    PubMed Central

    Favorov, O.V.; Li, Y.; Lee, J.; Quibrera, P.M.; Tommerdahl, M.

    2010-01-01

    Procedures that reliably evoke cutaneous pain in humans (i.e., 5–7 s skin contact with a 47–51 °C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RFcenter) when stimulus amplitude is “near-threshold” (i.e., 10–50 μm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47–51 °C contact or intradermal algogen injection when the amplitude of 25-Hz stimulation is 100–200 μm (suprathreshold). The results are attributed to an “activity dependence” of γ-aminobutyric acid (GABA) action on the GABAA receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47–51 °C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RFcenter stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold). PMID:20308203

  17. Role of the vagus nerve in the development and treatment of diet‐induced obesity

    PubMed Central

    2016-01-01

    Abstract This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie‐rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high‐fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade‐induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity. PMID:26959077

  18. Role of the NH2-terminus of substance P in the inhibition by capsaicin of behavioral sensitization to kainic acid-induced activity in the adult mouse.

    PubMed

    Larson, A A; Sun, X

    1994-01-01

    Activation of primary afferent C-fibers by repeated intrathecal injection of kainic acid (KA) in mice is inhibited after pretreatment with capsaicin. The increased behavioral response to multiple injections of KA is thought to be brought about by an action of the NH2-terminus of substance P (SP). In light of our recent observation that the antinociceptive effect of capsaicin may also involve an action of the NH2-terminus of SP, we tested the hypothesis that capsaicin inhibits behavioral sensitization to KA by a desensitization to the action of the NH2-terminus of SP. Using adult mice, pretreatment (24 hr) with either capsaicin (0.8 micrograms) or SP(1-7) (1 and 10 nmol) attenuated sensitization of the behavioral response to four injections of 25 pmol of KA at 2-min intervals. Pretreatment with 10 nmol of the COOH-terminal SP fragment, SP(5-11), had no effect. [D-Pro2,D-Phe7]-SP(1-7), a SP NH2-terminal antagonist, injected 5 min before capsaicin or SP(1-7), inhibited the effects of both capsaicin and SP(1-7) on KA sensitization whereas the COOH-terminal neurokinin antagonist, [D-Pro2,D-Trp7,9]-SP, did not. The similarities in behavioral responses after treatment with SP(1-7) or capsaicin, together with the sensitivity of these effects to D-SP(1-7), suggest that SP released in response to capsaicin may inhibit subsequent KA-induced activity 24 hr later. This action of SP appears to be brought about by its NH2-terminus and/or an accumulation of its NH2-terminal metabolites after capsaicin treatment.

  19. Use of social adaptability index to explain self-care and diabetes outcomes.

    PubMed

    Campbell, Jennifer A; Walker, Rebekah J; Smalls, Brittany L; Egede, Leonard E

    2017-06-20

    To examine whether the social adaptability index (SAI) alone or components of the index provide a better explanatory model for self-care and diabetes outcomes. Six hundred fifteen patients were recruited from two primary care settings. A series of multiple linear regression models were run to assess (1) associations between the SAI and diabetes self-care/outcomes, and (2) associations between individual SAI indicator variables and diabetes self-care/outcomes. Separate models were run for each self-care behavior and outcome. Two models were run for each dependent variable to compare associations with the SAI and components of the index. The SAI has a significant association with the mental component of quality of life (0.23, p < 0.01). In adjusted analyses, the SAI score did not have a significant association with any of the self-care behaviors. Individual components from the index had significant associations between self-care and multiple SAI indicator variables. Significant associations also exist between outcomes and the individual SAI indicators for education and employment. In this population, the SAI has low explanatory power and few significant associations with diabetes self-care/outcomes. While the use of a composite index to predict outcomes within a diabetes population would have high utility, particularly for clinical settings, this SAI lacks statistical and clinical significance in a representative diabetes population. Based on these results, the index does not provide a good model fit and masks the relationship of individual components to diabetes self-care and outcomes. These findings suggest that five items alone are not adequate to explain or predict outcomes for patients with type 2 diabetes.

  20. Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model

    PubMed Central

    Marquet, Florian; Bonneau, Michel; Pascale, Florentina; Urien, Celine; Kang, Chantal; Schwartz-Cornil, Isabelle; Bertho, Nicolas

    2011-01-01

    Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163neg/CD172aneg, (2) the CD163highCD172apos and (3) the CD163lowCD172apos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163negCD172low DDC share properties with the CD8+ T cell response-inducing murine skin CD103pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC. PMID:21298011