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Sample records for afferent pupillary response

  1. The afferent pupillary defect in acute optic neuritis.

    PubMed Central

    Ellis, C J

    1979-01-01

    Twenty-two patients with acute optic neuritis were studied by the techniques of infrared pupillometry and visual evoked responses (VER) to pattern reversal. A relative afferent pupillary defect was found in all cases and the magnitude of this defect was found to be related to the amplitude, but not to the latency, of the VER. During follow-up the afferent defect was found to remain persistently abnormal while other methods of clinical evaluation could not demonstrate abnormality reliably. The amplitude of the VER also remained low. PMID:501365

  2. Auditory-pupillary responses in deaf subjects.

    PubMed

    Kitajima, Naoharu; Otsuka, Koji; Ogawa, Yasuo; Shimizu, Shigetaka; Hayashi, Mami; Ichimura, Akihide; Suzuki, Mamoru

    2010-01-01

    Pupillary dilation in response to sound stimuli is well established and is generally considered to represent a startle reflex to sound. We believe that the auditory-pupillary response represents not only a simple startle reflex to sound stimuli but also represents a reaction to stimulation of other sense organs, such as otolith organs. Eight young healthy volunteers without a history of hearing and equilibrium problems and 12 subjects with bilateral deafness participated in this study. Computer pupillography was used to analyze the auditory-pupillary responses of both eyes in all subjects. We found that auditory-pupillary responses occurred even in subjects with bilateral deafness and that this response was comparable to those of normal subjects. We propose that the auditory-pupillary response also relates to vestibular function. Thus, assessing the auditory-pupillary response may be useful for evaluating the vestibulo-autonomic response in patients with peripheral disequilibrium. PMID:20826936

  3. Estimation of Retinal Ganglion Cell Loss in Glaucomatous Eyes With a Relative Afferent Pupillary Defect

    PubMed Central

    Tatham, Andrew J.; Meira-Freitas, Daniel; Weinreb, Robert N.; Marvasti, Amir H.; Zangwill, Linda M.; Medeiros, Felipe A.

    2014-01-01

    Purpose. To estimate retinal ganglion cell (RGC) losses associated with a relative afferent pupillary defect (RAPD) in glaucoma. Methods. A cross-sectional study was conducted including both eyes of 103 participants from the Diagnostic Innovations in Glaucoma Study. A total of 77 subjects had glaucoma in at least one eye and 26 were healthy. Pupil responses were assessed using an automated pupillometer that records the magnitude of RAPD as an “RAPD score.” Standard automated perimetry (SAP) and optical coherence tomography (OCT) also were performed. Retinal ganglion cell counts were estimated using empirical formulas that combine estimates from SAP and OCT. The estimated percentage RGC loss was calculated using the combined structure function index (CSFI). Results. There was good correlation between RAPD magnitude and intereye differences in estimated RGCs (R2 = 0.492, P < 0.001), mean deviation (R2 = 0.546, P < 0.001), retinal nerve fiber layer thickness (R2 = 0.362, P < 0.001), and CSFI (R2 = 0.484, P < 0.001). Therefore, a high RAPD score is likely to indicate large asymmetric RGC losses. The relationship between intereye difference in RGC counts and RAPD score was described best by the formula; RGC difference = 21,896 + 353,272 * RAPD score. No healthy subjects had an absolute RAPD score > 0.3, which was associated with asymmetry of 105,982 cells (or 12%). Conclusions. Good correlation between the magnitude of RAPD and intereye differences in mean deviation and estimated RGC counts suggests pupillometry may be useful for quantifying asymmetric damage in glaucoma. (ClinicalTrials.gov number, NCT00221897.) PMID:24282221

  4. Predictive value of visual evoked potentials, relative afferent pupillary defect, and orbital fractures in patients with traumatic optic neuropathy

    PubMed Central

    Tabatabaei, Seyed Ali; Soleimani, Mohammad; Alizadeh, Mahdi; Movasat, Morteza; Mansoori, Mohammad Reza; Alami, Zakieh; Foroutan, Alireza; Joshaghani, Mahmood; Safari, Saeid; Goldiz, Arzhang

    2011-01-01

    Background: The purpose of this study was to determine the predictive value of flash visual-evoked potentials (VEP), relative afferent pupillary defect, and presence of orbital fractures in patients with traumatic optic neuropathy. Methods: A prospective study was conducted in 15 patients with indirect traumatic optic neuropathy. All patients underwent a thorough ophthalmic examination. Initial visual acuity, final visual acuity, and relative afferent pupillary defect were determined, and visual acuity was converted into logMAR units. We performed flash VEP and an orbital computed tomography scan in all patients. Results: There was a good correlation between relative afferent pupillary defect and final visual acuity (r = −0.83), and better initial visual acuity could predict better final visual acuity (r = 0.92). According to findings from flash VEP parameters, there was a relationship between final visual acuity and amplitude ratio of the wave (r = 0.59) and latency ratio of the wave (r = −0.61). Neither primary visual acuity nor final visual acuity was related to the presence of orbital fractures in the orbital CT scan. Conclusion: Patients with traumatic optic neuropathy often present with severe vision loss. Flash VEP, poor initial visual acuity, and higher grade of relative afferent pupillary defect could predict final visual acuity in these patients. Presence of orbital fracture was not a predictive factor for primary visual acuity or final visual acuity. PMID:21845028

  5. Correlation of afferent pupillary defect with visual field loss on automated perimetry.

    PubMed

    Johnson, L N; Hill, R A; Bartholomew, M J

    1988-12-01

    The study was designed to ascertain the relationship between visual loss in the central 30 degrees of vision and the density of the relative afferent pupillary defect (APD). The APD of 26 patients was quantified using a neutral log density filter. The mean threshold light sensitivity on Humphrey automated perimetry (Program 30-1) of one eye was substracted from the fellow eye total to yield the interocular visual field difference (VFD). A direct correlation was noted such that the log density of the APD increased linearly with an increase in VFD (r = 0.69, P = 0.0001). In the absence of ptosis or ocular media opacification, a VFD greater than 8.7 that is not associated with an APD is suggestive of functional visual loss. Four patients had an APD despite normal static automated perimetry, indicating that an APD may be one of the earliest signs of retinal ganglion cell or axonal dysfunction. PMID:3068603

  6. Evidence for preserved direct pupillary light response in Leber's hereditary optic neuropathy.

    PubMed Central

    Wakakura, M; Yokoe, J

    1995-01-01

    AIMS/BACKGROUND--Pupillary light response is usually defective in all types of optic neuropathy. However, the authors have observed in patients with Leber's hereditary optic neuropathy (LHON) relatively normal light response, with consequent misdiagnosis psychogenic visual loss in some cases. To confirm this clinical impression, afferent pupillary defect was assessed by measurement of adjusted constriction amplitude (CA) and escape rate (ER) by infrared videopupillography (Iriscorder-C 2515). METHODS--Thirteen consecutive patients (26 eyes) with LHON (average age 27.2 years) were examined; 12 had the mitochondrial DNA 11778 mutation and one the 14484 mutation. Seven of these patients had a positive family history. For comparison, the above rates were determined in 19 patients (23 eyes) with idiopathic optic neuritis (ON; average age 35.1 years), 18 patients (19 eyes) with anterior ischaemic optic neuropathy (AION; average age 58.1 years), and 25 volunteers (50 eyes) with healthy eyes (average age 39.6 years). RESULTS--The distribution of visual acuity was essentially the same in all optic neuropathy groups. Reduction in CA and increase in ER were significant in patients with ON and AION, but not in those with LHON. Only slight afferent pupillary defect was evident even 2 years after the onset of LHON. CA in AION and ER in ON were correlated statistically with visual acuity and Humphrey mean threshold deviation, while CA and ER in LHON were not. CONCLUSION--Pupillary light response in patients with LHON obviously differs from that in patients with other types of optic neuropathy. LHON appears to be pathophysiologically characterised by well preserved afferent fibres for pupillary light response (probably from W cells). Besides being of pathogenetic interest, the detection of clinical features should facilitate the diagnosis of LHON particularly when family history provides no indication. PMID:7612556

  7. Sociometric Choice: A Study in Pupillary Response.

    ERIC Educational Resources Information Center

    Koff, Robert H.; Hawkes, Thomas H.

    Pupillary dilatation has recently been reported as a physiological measure of degree of attention paid to environmental stimuli (Hess and Polt, 1960, 1964). Hess and Polt's research has operationally defined one variable and has provided data that allows researchers to speculate about several others. This variable is interest-disinterest. The…

  8. Dissociable saccadic suppression of pupillary and perceptual responses to light.

    PubMed

    Benedetto, Alessandro; Binda, Paola

    2016-03-01

    We measured pupillary constrictions in response to full-screen flashes of variable luminance, occurring either at the onset of a saccadic eye movement or well before/after it. A large fraction of perisaccadic flashes were undetectable to the subjects, consistent with saccadic suppression of visual sensitivity. Likewise, pupillary responses to perisaccadic flashes were strongly suppressed. However, the two phenomena appear to be dissociable. Across subjects and luminance levels of the flash stimulus, there were cases in which conscious perception of the flash was completely depleted yet the pupillary response was clearly present, as well as cases in which the opposite occurred. On one hand, the fact that pupillary light responses are subject to saccadic suppression reinforces evidence that this is not a simple reflex but depends on the integration of retinal illumination with complex "extraretinal" cues. On the other hand, the relative independence of pupillary and perceptual responses suggests that suppression acts separately on these systems-consistent with the idea of multiple visual pathways that are differentially affected by saccades. PMID:26745249

  9. Pupillary responses to intranasal trigeminal and olfactory stimulation.

    PubMed

    Schneider, Christine B; Ziemssen, Tjalf; Schuster, Benno; Seo, Han-Seok; Haehner, Antje; Hummel, Thomas

    2009-07-01

    The aim of the present study was to investigate whether pupillary responses to odorous stimuli reflect their intensity or hedonic tone. A total of 21 healthy subjects participated in the study. Using a computer-controlled olfactometer, subjects received intranasal stimuli including odors of rose (PEA; 2 concentrations), lemon and rotten eggs, plus the trigeminal irritant CO2 (also at two concentrations). Changes in the pupil diameter were obtained ipsilaterally to the side of stimulus presentation. Both trigeminal and olfactory stimulation produced an increase in pupillary diameter. Latencies for pupillary reaction were fastest for the higher concentration of CO2 and slowest after the presentation of PEA at the low concentration. Response amplitudes were largest in response to stimulation with CO2 at the high concentration, while they were smallest in response to odorous stimulation with PEA. Response latencies decreased with increasing stimulus intensity. No such correlation was found for hedonic ratings and pupillary reactions. Thus, the change in the pupillary diameter indicates differences between stimulus modalities and stimulus strength, but not pleasantness or unpleasantness of the odors. PMID:19484181

  10. Association between a relative afferent pupillary defect using pupillography and inner retinal atrophy in optic nerve disease

    PubMed Central

    Takizawa, Go; Miki, Atsushi; Maeda, Fumiatsu; Goto, Katsutoshi; Araki, Syunsuke; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

    2015-01-01

    Purpose The aim of this study was to compare the asymmetrical light reflex of the control subjects and patients with optic nerve disease and to evaluate the relationships among the relative afferent pupillary defect (RAPD), visual acuity (VA), central critical fusion frequency (CFF), ganglion cell complex thickness (GCCT), and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using spectral-domain optical coherence tomography. Materials and methods Using a pupillography device, the RAPD scores from 15 patients with unilateral optic nerve disease and 35 control subjects were compared. The diagnostic accuracy of the RAPD amplitude and latency scores was compared using the area under the receiver operating characteristic curve. Thereafter, we assessed the relationships among the RAPD scores, VA, central CFF, GCCT, and cpRNFLT. Results The average RAPD amplitude score in patients with optic nerve disease was significantly higher than that of the control subjects (P<0.001). The average RAPD latency score in patients with optic nerve disease was significantly higher than that of the control subjects (P=0.001). The area under the receiver operating characteristic curve for the RAPD amplitude score was significantly higher than that for the latency score (P=0.010). The correlation coefficients for the RAPD amplitude and latency scores were 0.847 (P<0.001) and 0.874 (P<0.001) for VA, −0.868 (P<0.001) and −0.896 (P<0.001) for central CFF, −0.593 (P=0.020) and −0.540 (P=0.038) for GCCT, and −0.267 (P=0.337) and −0.228 (P=0.413) for cpRNFLT, respectively. Conclusion Our results suggest that pupillography is useful for detecting optic nerve disease. PMID:26487800

  11. The pupillary light response reflects eye-movement preparation.

    PubMed

    Mathôt, Sebastiaan; van der Linden, Lotje; Grainger, Jonathan; Vitu, Françoise

    2015-02-01

    When the eyes are exposed to an increased influx of light, the pupils constrict. The pupillary light response (PLR) is traditionally believed to be purely reflexive and not susceptible to cognitive influences. In contrast to this traditional view, we report that preparation of a PLR occurs in parallel with preparation of a saccadic eye movement toward a bright (or dark) stimulus, even before the eyes set in motion. Participants fixated a central gray area and made a saccade toward a peripheral target. Using gaze-contingent display changes, we manipulated whether or not the brightness of the target background was the same during and after saccade preparation. More specifically, on some trials we changed the brightness of the target background during the saccade, thus dissociating the preparatory PLR (i.e., to the brightness of the target background before the saccade) from the regular PLR (i.e., to the brightness after the saccade). We show that preparation triggers a pupillary response to the brightness of a to-be-fixated target background already before the eyes have landed on it. We link our findings to the presaccadic shift of attention: The pupil prepares to adjust its size to the brightness of a to-be-fixated stimulus as soon as attention covertly shifts toward that stimulus. Our findings illustrate that the PLR is a dynamic movement that is tightly linked to visual attention and eye-movement preparation. PMID:25621584

  12. The pupillary light response reveals the focus of covert visual attention.

    PubMed

    Mathôt, Sebastiaan; van der Linden, Lotje; Grainger, Jonathan; Vitu, Françoise

    2013-01-01

    The pupillary light response is often assumed to be a reflex that is not susceptible to cognitive influences. In line with recent converging evidence, we show that this reflexive view is incomplete, and that the pupillary light response is modulated by covert visual attention: Covertly attending to a bright area causes a pupillary constriction, relative to attending to a dark area under identical visual input. This attention-related modulation of the pupillary light response predicts cuing effects in behavior, and can be used as an index of how strongly participants attend to a particular location. Therefore, we suggest that pupil size may offer a new way to continuously track the focus of covert visual attention, without requiring a manual response from the participant. The theoretical implication of this finding is that the pupillary light response is neither fully reflexive, nor under complete voluntary control, but is instead best characterized as a stereotyped response to a voluntarily selected target. In this sense, the pupillary light response is similar to saccadic and smooth pursuit eye movements. Together, eye movements and the pupillary light response maximize visual acuity, stabilize visual input, and selectively filter visual information as it enters the eye. PMID:24205144

  13. Executive control suppresses pupillary responses to aversive stimuli.

    PubMed

    Cohen, Noga; Moyal, Natali; Henik, Avishai

    2015-12-01

    Adaptive behavior depends on the ability to effectively regulate emotional responses. Continuous failure in the regulation of emotions can lead to heightened physiological reactions and to various psychopathologies. Recently, several behavioral and neuroimaging studies showed that exertion of executive control modulates emotion. Executive control is a high-order operation involved in goal-directed behavior, especially in the face of distractors or temptations. However, the role of executive control in regulating emotion-related physiological reactions is unknown. Here we show that exercise of executive control modulates reactivity of both the sympathetic and the parasympathetic components of the autonomic nervous system. Specifically, we demonstrate that both pupillary light reflex and pupil dilation for aversive stimuli are attenuated following recruitment of executive control. These findings offer new insights into the very basic mechanisms of emotion processing and regulation, and can lead to novel interventions for people suffering from emotion dysregulation psychopathologies. PMID:26410694

  14. Vestibular afferent responses to microrotational stimuli

    NASA Technical Reports Server (NTRS)

    Myers, Steven F.; Lewis, Edwin R.

    1991-01-01

    Intracellular microelectrode recording/labeling techniques were used to investigate vestibular afferent responses in the bullfrog, to very small amplitude (less than 5 deg p-p) sinusoidal rotations in the vertical plane over the frequency range of 0.063-4 Hz. Robust responses to peak accelerations as low as 0.031 deg/sec per sec were obtained from units subsequently traced to either the central portion of the anterior canal crista or the striolar region of the utricle. All of these microrotationally sensitive afferent neurons had irregular resting discharge rates, and the majority had transfer ratios (relative to rotational velocity) of 1-40 spikes/sec per deg/sec. Individual utricular afferent velocity transfer ratios were nearly constant over the frequency range of 0.125-4 Hz. Canal units displayed decreasing response transfer ratios as stimulus frequencies increased. These findings indicate that, although utricular striolar and central crista afferent velocity transfer ratios to microrotations were very similar, utricular striolar afferent neurons were more faithful sensors of very small amplitude rotational velocity in the vertical plane.

  15. Correspondences among pupillary dilation response, subjective salience of sounds, and loudness.

    PubMed

    Liao, Hsin-I; Kidani, Shunsuke; Yoneya, Makoto; Kashino, Makio; Furukawa, Shigeto

    2016-04-01

    A pupillary dilation response is known to be evoked by salient deviant or contrast auditory stimuli, but so far a direct link between it and subjective salience has been lacking. In two experiments, participants listened to various environmental sounds while their pupillary responses were recorded. In separate sessions, participants performed subjective pairwise-comparison tasks on the sounds with respect to their salience, loudness, vigorousness, preference, beauty, annoyance, and hardness. The pairwise-comparison data were converted to ratings on the Thurstone scale. The results showed a close link between subjective judgments of salience and loudness. The pupil dilated in response to the sound presentations, regardless of sound type. Most importantly, this pupillary dilation response to an auditory stimulus positively correlated with the subjective salience, as well as the loudness, of the sounds (Exp. 1). When the loudnesses of the sounds were identical, the pupil responses to each sound were similar and were not correlated with the subjective judgments of salience or loudness (Exp. 2). This finding was further confirmed by analyses based on individual stimulus pairs and participants. In Experiment 3, when salience and loudness were manipulated by systematically changing the sound pressure level and acoustic characteristics, the pupillary dilation response reflected the changes in both manipulated factors. A regression analysis showed a nearly perfect linear correlation between the pupillary dilation response and loudness. The overall results suggest that the pupillary dilation response reflects the subjective salience of sounds, which is defined, or is heavily influenced, by loudness. PMID:26163191

  16. The Eye is Listening: Music-Induced Arousal and Individual Differences Predict Pupillary Responses.

    PubMed

    Gingras, Bruno; Marin, Manuela M; Puig-Waldmüller, Estela; Fitch, W T

    2015-01-01

    Pupillary responses are a well-known indicator of emotional arousal but have not yet been systematically investigated in response to music. Here, we measured pupillary dilations evoked by short musical excerpts normalized for intensity and selected for their stylistic uniformity. Thirty participants (15 females) provided subjective ratings of music-induced felt arousal, tension, pleasantness, and familiarity for 80 classical music excerpts. The pupillary responses evoked by these excerpts were measured in another thirty participants (15 females). We probed the role of listener-specific characteristics such as mood, stress reactivity, self-reported role of music in life, liking for the selected excerpts, as well as of subjective responses to music, in pupillary responses. Linear mixed model analyses showed that a greater role of music in life was associated with larger dilations, and that larger dilations were also predicted for excerpts rated as more arousing or tense. However, an interaction between arousal and liking for the excerpts suggested that pupillary responses were modulated less strongly by arousal when the excerpts were particularly liked. An analogous interaction was observed between tension and liking. Additionally, males exhibited larger dilations than females. Overall, these findings suggest a complex interplay between bottom-up and top-down influences on pupillary responses to music. PMID:26617511

  17. The Eye is Listening: Music-Induced Arousal and Individual Differences Predict Pupillary Responses

    PubMed Central

    Gingras, Bruno; Marin, Manuela M.; Puig-Waldmüller, Estela; Fitch, W. T.

    2015-01-01

    Pupillary responses are a well-known indicator of emotional arousal but have not yet been systematically investigated in response to music. Here, we measured pupillary dilations evoked by short musical excerpts normalized for intensity and selected for their stylistic uniformity. Thirty participants (15 females) provided subjective ratings of music-induced felt arousal, tension, pleasantness, and familiarity for 80 classical music excerpts. The pupillary responses evoked by these excerpts were measured in another thirty participants (15 females). We probed the role of listener-specific characteristics such as mood, stress reactivity, self-reported role of music in life, liking for the selected excerpts, as well as of subjective responses to music, in pupillary responses. Linear mixed model analyses showed that a greater role of music in life was associated with larger dilations, and that larger dilations were also predicted for excerpts rated as more arousing or tense. However, an interaction between arousal and liking for the excerpts suggested that pupillary responses were modulated less strongly by arousal when the excerpts were particularly liked. An analogous interaction was observed between tension and liking. Additionally, males exhibited larger dilations than females. Overall, these findings suggest a complex interplay between bottom-up and top-down influences on pupillary responses to music. PMID:26617511

  18. Attenuation of the pupillary response to luminance and color changes during interocular suppression.

    PubMed

    Kimura, Eiji; Abe, Satoru; Goryo, Ken

    2014-01-01

    The present study investigated the effects of interocular suppression on the pupillary constriction to luminance and color changes. Stable interocular suppression was produced by presenting a flickering high-contrast grating to one eye and a spatially homogeneous field to the other eye. The results showed that the pupillary responses to luminance as well as color changes were clearly attenuated during interocular suppression; the pupillary constriction to stimulus changes was delayed and reduced in amplitude when those changes occurred in the suppressed eye. The attenuation of the pupillary response was observed over a wide range of test contrast extending to well above the threshold level. Moreover, the properties of the suppressive effect were very similar to those assessed psychophysically using both detection thresholds for weak stimuli and reaction times for suprathreshold stimuli. Overall, the present study provided converging evidence that the pupillary response can be a useful objective probe of interocular suppression in humans. The results are discussed in view of possible differential involvements of subcortical and cortical visual processing in driving the pupillary response as well as in interocular suppression. PMID:24879861

  19. Spatial attention increases the pupillary response to light changes.

    PubMed

    Binda, Paola; Murray, Scott O

    2015-01-01

    We measured pupil size in adult human subjects while we manipulated both the luminance of the visual scene and the location of attention. We found that, with central fixation maintained, pupillary constrictions and dilations evoked by peripheral luminance increments and decrements are larger when spatial attention is covertly (i.e., with no eye movements) directed to the stimulus region versus when it is directed to the opposite hemifield. Irrespective of the size of the attended region (focused at the center of the stimulus or spread within and outside the stimulus), the attentional enhancement is large: more than 20% of the response to stimuli in the unattended hemifield. This indicates that a sizable portion of this simple ocular behavior—often considered a subcortical "reflex"—in fact depends on cortical processing. Together, these features indicate that pupillometry is not only an index of retinal and brainstem function, but also an objective measure of complex constructs such as attention and its effects on sensory processing. PMID:25645434

  20. Depressed Adolescents' Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination.

    PubMed

    Stone, Lindsey B; Silk, Jennifer S; Siegle, Greg J; Lee, Kyung Hwa; Stroud, Laura R; Nelson, Eric E; Dahl, Ronald E; Jones, Neil P

    2016-06-01

    Heightened emotional reactivity to peer feedback is predictive of adolescents' depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents' physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12-17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback. PMID:26271345

  1. Visual pigment processes and prolonged pupillary responses in insect photoreceptor cells.

    PubMed

    Stavenga, D G

    1979-01-01

    The visual pigment in the peripheral retinular cells of the hoverfly Syrphus balteatus was investigated by absorbance difference measurements. Different visual pigments were found in the dorsal versus the ventral part of the eye in the male, but not in the female. In the male in the dorsal part of the eye the visual pigment has an isosbestic point at 513 nm; in the ventral part this value is 490 nm. The latter value is found in the female in both parts of the eye. Prolonged pupillary responses were studied in the male Syrphus and appeared to be most marked in the ventral part of the eye. In both hoverfly and blowfly prolonged pupillary responses are induced by short wavelength light only; i.e., by light which excessively can convert rhodopsin into metarhodopsin. By contrast, in butterflies red light (and a long dark adaptation time) is necessary to evoke a prolonged pupillary response. It was demonstrated in both hoverfly and blowfly that long wavelength light, which reconverts metarhodopsin into rhodopsin, inhibits a prolonged pupillary response; or, accelerates pupil opening. PMID:22730591

  2. Effects of Age and Sex on Values Obtained by RAPDx® Pupillometer, and Determined the Standard Values for Detecting Relative Afferent Pupillary Defect

    PubMed Central

    Satou, Tsukasa; Goseki, Toshiaki; Asakawa, Ken; Ishikawa, Hitoshi; Shimizu, Kimiya

    2016-01-01

    Purpose To determine the effects of age and sex on the amplitude and latency scores obtained by the RAPDx® pupillometer, and to determine the standard values for detecting relative afferent pupillary defect (RAPD) in healthy subjects. Methods The study was conducted on 84 healthy subjects (52 males, 32 females), who had no ophthalmic diseases other than refractive errors with a mean age of 32 years. The amplitude and latency scores of the males were compared to that of females and also among the different age groups. The correlations between the amplitude and latency scores and age were determined. The standard values with the 90%, 95%, and 99% prediction intervals of the measured values were also calculated. Results The differences in the amplitude and latency scores between the sexes were not significant. In addition, both scores were not significantly related with age. The mean amplitude score for all subjects with prediction intervals of 90%, 95%, and 99% was 0.02 (−0.26 to 0.30, −0.32 to 0.35, and −0.42 to 0.46, respectively); the latency score was −0.02 (−0.24 to 0.20, −0.28 to 0.25, and −0.37 to 0.33, respectively). Conclusions RAPD is not present when the absolute values of the amplitude score and latency scores, measured by the RAPDx® pupillometer, are ≤ 0.2 log units. RAPD is present when either of the values are ≥ 0.5 log units. Translational Relevance Results of this study can be used for detection of RAPD in the clinic and it will be the basic data of RAPDx® pupillometer for future research. PMID:27152248

  3. Response properties of pigeon otolith afferents to linear acceleration

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    In the present study, the sensitivity to sinusoidal linear accelerations in the plane of the utricular macula was tested in afferents. The head orientation relative to the translation axis was varied in order to determine the head position that elicited the maximal and minimal responses for each afferent. The response gain and phase values obtained to 0.5-Hz and 2-Hz linear acceleration stimuli were then plotted as a function of head orientation and a modified cosine function was fit to the data. From the best-fit cosine function, the predicted head orientations that would produce the maximal and minimal response gains were estimated. The estimated maximum response gains to linear acceleration in the utricular plane for the afferents varied between 75 and 1420 spikes s-1 g-1. The mean maximal gains for all afferents to 0.5-Hz and 2-Hz sinusoidal linear acceleration stimuli were 282 and 367 spikes s-1 g-1, respectively. The minimal response gains were essentially zero for most units. The response phases always led linear acceleration and remained constant for each afferent, regardless of head orientation. These response characteristics indicate that otolith afferents are cosine tuned and behave as one-dimensional linear accelerometers. The directions of maximal sensitivity to linear acceleration for the afferents varied throughout the plane of the utricle; however, most vectors were directed out of the opposite ear near the interaural axis. The response dynamics of the afferents were tested using stimulus frequencies ranging between 0.25 Hz and 10 Hz (0.1 g peak acceleration). Across stimulus frequencies, most afferents had increasing gains and constant phase values. These dynamic properties for individual afferents were fit with a simple transfer function that included three parameters: a mechanical time constant, a gain constant, and a fractional order distributed adaptation operator.

  4. The pupillary light response reflects exogenous attention and inhibition of return.

    PubMed

    Mathôt, Sebastiaan; Dalmaijer, Edwin; Grainger, Jonathan; Van der Stigchel, Stefan

    2014-01-01

    Here we show that the pupillary light response reflects exogenous (involuntary) shifts of attention and inhibition of return. Participants fixated in the center of a display that was divided into a bright and a dark half. An exogenous cue attracted attention to the bright or dark side of the display. Initially, the pupil constricted when the bright, as compared to the dark, side of the display was cued, reflecting a shift of attention toward the exogenous cue. Crucially, this pattern reversed about 1 s after cue presentation. This later-occurring, relative dilation (when the bright side was cued) reflected disengagement from the previously attended location, analogous to the behavioral phenomenon of inhibition of return. Indeed, we observed a reliable correlation between "pupillary inhibition" and behavioral inhibition of return. Our results support the view that inhibition of return results from habituation to (or short-term depression of) visual input. We conclude that the pupillary light response is a complex eye movement that reflects how we selectively parse and interpret visual input. PMID:25761284

  5. The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors

    PubMed Central

    Murphy, Peter R.; van Moort, Marianne L.; Nieuwenhuis, Sander

    2016-01-01

    Reaction time (RT) is commonly observed to slow down after an error. This post-error slowing (PES) has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES. PMID:27010472

  6. Novelty and emotion: Pupillary and cortical responses during viewing of natural scenes.

    PubMed

    Ferrari, Vera; De Cesarei, Andrea; Mastria, Serena; Lugli, Luisa; Baroni, Giulia; Nicoletti, Roberto; Codispoti, Maurizio

    2016-01-01

    Given the remarkable similarities in the antecedent conditions-stimulus motivational relevance and novelty (i.e., probability of occurrence)-that elicit amplitude modulation of the late positive potential (LPP) and the pupillary dilation response, the present study examines whether these two indexes of orienting response reflect common processes that are responsible for modulatory patterns in motivationally relevant contexts. In the present study, the LPP and the pupillary dilation response were co-registered in a free-picture viewing context in which stimulus novelty was manipulated through repeated presentation of the same picture exemplar. More specifically, pictures depicting both emotional and neutral contents could be novel, that is never seen before in the course of the study, or repeated 4-8 times in a row (i.e., massed repetition). Results showed that, despite massed repetitions, the late positive potential amplitude continued to be highly modulated by picture content, whereas affective modulation of pupil dilation decreased with picture repetition. These findings indicate that, although the LPP and pupil dilation are similarly affected by motivational relevance during the viewing of novel pictures, they differ when pictures are highly familiar, possibly reflecting different functional meanings in the context of the orienting response. PMID:26631353

  7. Video-Oculography To Obtain Pupillary Responses In the Visible Spectrum

    NASA Astrophysics Data System (ADS)

    Rodríguez, Dolores; Zúñiga, Arturo; Suaste, Ernesto

    2004-09-01

    Pupillary response (PR) of 20 healthy subjects (3 women and 17 men), was assessed using a chromatic stimulus in a visible spectrum (400-650 nm). The method consists in displaying two chromatics normalized software on a PC monitor under photopic conditions. The luminance of the PC monitor is calibrated with a photometer. This PC monitor was placed at 30 cm from the eye of the subject, while the subject watches it, the consensual reflex is recorded with a video-oculography system (VOG). This system is based on a video camera operated in night shoot function. The first software displays during 6 seconds a stimulus of a specific wavelength of the continuous range of spectral colors (the visible spectrum), spaced of 10 by 10 nm, beginning at 410 and ending at 660 nm. The second test, displays the same wavelength, but beginning at 400 and ending at 650, and present a black stimulus of 12 seconds of duration, between color stimulus. Once obtained the PR to each specific wavelength, we process the images and we obtain graphics that shows: a) the variations of the pupillary area, b) the percentage of dilatation, and c) the transitory response (TR) of the pupil of the subjects. We conclude that the second software (6s color stimulus — 12s black stimulus) is better to observe the changes of the PR due to each wavelength, because it allows the TR of the pupil: obtaining this way the characteristic curves of pupil responses to a light stimulus.

  8. Evaluation of pupillary response to light in patients with glaucoma: a study using computerized pupillometry.

    PubMed

    Martucci, Alessio; Cesareo, Massimo; Napoli, Domenico; Sorge, Roberto Pietro; Ricci, Federico; Mancino, Raffaele; Nucci, Carlo

    2014-12-01

    The aim of this study was to evaluate pupillary response to light stimulation in patients with different stages of glaucoma using computerized pupillometry. We conducted a retrospective study on a group of 44 glaucoma patients who had undergone complete ophthalmological examination, visual field test (Humphrey SITA Standard 24-2) and monocular dynamic pupillometry (MonCV3 Metrovision). Eyes were classified into stages of glaucoma according to visual field damage using the Glaucoma Staging System 2. A group of 18 healthy subjects, homogeneous for age and sex with glaucoma patients, was used as a control. The following parameters were considered-latency and duration of contraction and dilatation; initial, minimum, maximum, and mean pupil diameter; amplitude of contraction; contraction and dilatation speed; and percent pupil contraction (PPC). PPC and pupil contraction speed and minimum diameter showed covariate correlation with the stages of glaucoma. The control group significantly differed from the stage 3 group in terms of PPC and from the stage 4 group in terms of minimum diameter. There were significant differences between the stage 5 group and stage 1, 2, 3 and control groups. Ordinal logistic regression showed a correlation between pupil contraction speed, minimum diameter, PPC, initial diameter and the stage of glaucoma. The study showed that glaucoma damage is associated with altered values of pupillary response to light. This event may be the consequence of the progressive loss of retinal ganglion cells and their axons induced by glaucoma. PMID:24550056

  9. 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.

  10. Pupillary responses reveal infants' discrimination of facial emotions independent of conscious perception.

    PubMed

    Jessen, Sarah; Altvater-Mackensen, Nicole; Grossmann, Tobias

    2016-05-01

    Sensitive responding to others' emotions is essential during social interactions among humans. There is evidence for the existence of subcortically mediated emotion discrimination processes that occur independent of conscious perception in adults. However, only recently work has begun to examine the development of automatic emotion processing systems during infancy. In particular, it is unclear whether emotional expressions impact infants' autonomic nervous system regardless of conscious perception. We examined this question by measuring pupillary responses while subliminally and supraliminally presenting 7-month-old infants with happy and fearful faces. Our results show greater pupil dilation, indexing enhanced autonomic arousal, in response to happy compared to fearful faces regardless of conscious perception. Our findings suggest that, early in ontogeny, emotion discrimination occurs independent of conscious perception and is associated with differential autonomic responses. This provides evidence for the view that automatic emotion processing systems are an early-developing building block of human social functioning. PMID:26896901

  11. Human Pupillary Dilation Response to Deviant Auditory Stimuli: Effects of Stimulus Properties and Voluntary Attention

    PubMed Central

    Liao, Hsin-I; Yoneya, Makoto; Kidani, Shunsuke; Kashino, Makio; Furukawa, Shigeto

    2016-01-01

    A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR) that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants' pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention. PMID:26924959

  12. Melanopsin and rod-cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans.

    PubMed

    Gooley, Joshua J; Ho Mien, Ivan; St Hilaire, Melissa A; Yeo, Sing-Chen; Chua, Eric Chern-Pin; van Reen, Eliza; Hanley, Catherine J; Hull, Joseph T; Czeisler, Charles A; Lockley, Steven W

    2012-10-10

    In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally sighted individuals (n = 24) with a blind individual lacking rod-cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod-cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 min during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1-4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared with exposure to continuous green light. Our findings demonstrate nonredundant roles for rod-cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance nonvisual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans. PMID:23055493

  13. Pupillary responses of chromatic stimulus in the visible spectrum 400 nm of 650 nm, in the stable state

    NASA Astrophysics Data System (ADS)

    Guzman, D. R.; Lopez, A. Z.; Gomez, E. S.

    2005-08-01

    an instrumental methodology was implemented to analyze the pupillary responses in the dilation and contraction process elicited by chromatic stimulus. Chromatic stimuli were employed in the visible spectrum from 400 nm to 650 nm. Three different stimulation software was developed and used in order to obtain a contrasted pupillary response PG0, PG12 and PG20. This test was applied to 39 subjects (29 male, 9 female and I child, 22-52 years and 6 years), 10 of them were stimulated with PG0, 21 were stimulated with PG12 and 16 with PG20. 6 subjects participate at least in 2 tests. Ishihara plates were exhibited to the Subjects before the stimulation, 37 of the present a normal vision color, I present deuteranopy.

  14. Classical Photoreceptors Are Primarily Responsible for the Pupillary Light Reflex in Mouse

    PubMed Central

    Jain, Varsha; Srivastava, Ipsit; Palchaudhuri, Shriya; Goel, Manvi; Sinha-Mahapatra, Sumit K.; Dhingra, Narender K.

    2016-01-01

    Pupillary light reflex (PLR) is an important clinical tool to assess the integrity of visual pathways. The available evidence suggests that melanopsin-expressing retinal ganglion cells (mRGCs) mediate PLR—driven by the classical photoreceptors (rods and cones) at low irradiances and by melanopsin activation at high irradiances. However, genetic or pharmacological elimination of melanopsin does not completely abolish PLR at high irradiances, raising the possibility that classical photoreceptors may have a role even at high irradiances. Using an inducible mouse model of photoreceptor degeneration, we asked whether classical photoreceptors are responsible for PLR at all irradiances, and found that the PLR was severely attenuated at all irradiances. Using multiple approaches, we show that the residual PLR at high irradiances in this mouse was primarily from the remnant rods and cones, with a minor contribution from melanopsin activation. In contrast, in rd1 mouse where classical photoreceptor degeneration occurs during development, the PLR was absent at low irradiances but intact at high irradiances, as reported previously. Since mRGCs receive inputs from classical photoreceptors, we also asked whether developmental loss of classical photoreceptors as in rd1 mouse leads to compensatory takeover of the high-irradiance PLR by mRGCs. Specifically, we looked at a distinct subpopulation of mRGCs that express Brn3b transcription factor, which has been shown to mediate PLR. We found that rd1 mouse had a significantly higher proportion of Brn3b-expressing M1 type of mRGCs than in the inducible model. Interestingly, inducing classical photoreceptor degeneration during development also resulted in a higher proportion of Brn3b-expressing M1 cells and partially rescued PLR at high irradiances. These results suggest that classical photoreceptors are primarily responsible for PLR at all irradiances, while melanopsin activation makes a minor contribution at very high irradiances

  15. Frequency analysis of a task-evoked pupillary response: Luminance-independent measure of mental effort.

    PubMed

    Peysakhovich, Vsevolod; Causse, Mickaël; Scannella, Sébastien; Dehais, Frédéric

    2015-07-01

    Pupil diameter is a widely-studied cognitive load measure, which, despite its convenience for non-intrusive operator state monitoring in complex environments, is still not available for in situ measurements because of numerous methodological limitations. The most important of these limitations is the influence of pupillary light reflex. Hence, there is the need of providing a pupil-based cognitive load measure that is independent of light conditions. In this paper, we present a promising technique of pupillary signal analysis resulting in luminance-independent measure of mental effort that could be used in real-time without a priori on luminous conditions. Twenty-two participants performed a short-term memory task under different screen luminance conditions. Our results showed that the amplitude of pupillary dilation due to load on memory was luminance-dependent with higher amplitude corresponding to lower-luminance condition. Furthermore, our experimentation showed that load on memory and luminance factors express themselves differently according to frequency. Therefore, as our statistical analysis revealed, the ratio between low (0-1.6 Hz) and high frequency (1.6-4 Hz) bands (LF/HF ratio) of power spectral densities of pupillary signal is sensitive to the cognitive load but not to luminance. Our results are promising for the measurement of load on memory in ecological settings. PMID:25941013

  16. 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.

  17. Enhancing Diagnostic Accuracy of aMCI in the Elderly: Combination of Olfactory Test, Pupillary Response Test, BDNF Plasma Level, and APOE Genotype

    PubMed Central

    Ranakusuma, Teguh Asaat S.; Purba, Jan Sudir; Amir, Nurmiati; Ahmad, Siti Airiza; Machfoed, Moh. Hasan; Handayani, Yvonne Suzy; Asmarinah; Waspadji, Sarwono

    2014-01-01

    Background. Amnestic Mild Cognitive Impairment (aMCI) often progresses to Alzheimer's disease. There are clinical markers and biomarkers to identify the degenerative process in the brain. Objectives. To obtain the diagnostic values of olfactory test, pupillary response to tropicamide 0.01%, BDNF plasma level, and APOE ε4 in diagnosing aMCI. Methods. Cross-sectional, comparative analysis. Results. There were 109 subjects enrolled (aMCI: 51, normal cognition: 58) with age 64 ± 5.54 years. For diagnosing aMCI, cut-off point for the olfactory score was <7 out of 10 and >22% for pupil dilatation response. Low BDNF plasma level was related significantly with olfactory deficits and aMCI (P < 0.05). Four of five subjects with homozygote e4 presented with multiple-domain aMCI. This group displayed the lowest means of olfactory score and the highest means of pupillary hypersensitivity response (P < 0.0001). Combination of olfactory deficit and pupillary hypersensitivity response in detection of aMCI was beneficial with Sp 91% and PPV 87%. In conjunction with clinical markers, BDNF plasma level and presence of APOE e4+ improved Sp and PPV. Conclusions. Combination of olfactory test and pupillary response test was useful as diagnostic tool in aMCI. In conjunction with clinical markers, low level of BDNF plasma and presence of APOE e4 improved the diagnostic value. PMID:24639912

  18. Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

    PubMed Central

    Macefield, G; Gandevia, S C; Burke, D

    1990-01-01

    1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the

  19. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish.

    PubMed

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander; Liao, James C

    2015-01-15

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  20. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish

    PubMed Central

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander

    2014-01-01

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  1. Response properties of gerbil otolith afferents to small angle pitch and roll tilts

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    The responses from isolated single otolith afferent fibers were obtained to small angle sinusoidal pitch and roll tilts in anesthetized gerbils. The stimulus directions that produced the maximum (response vector) and minimum response sensitivities were determined for each otolith afferent, with response vectors for the units being spread throughout the horizontal plane, similar to those reported for other species. A breadth of tuning measure was derived, with narrowly tuned neurons responding maximally to stimulation in one direction and minimally along an orthogonal ('null') direction. Most (approximately 80%) otolith afferents are narrowly tuned, however, some fibers were broadly tuned responding significantly to stimulations in any direction in the horizontal plane. The number of broadly tuned otolith afferents (approximately 20%) differs significantly from the more substantial number of broadly tuned vestibular nuclei neurons (88%) recently reported in rats.

  2. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    PubMed

    Reijntjes, Daniël O J; Pyott, Sonja J

    2016-06-01

    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  3. Activation of guanylate cyclase-C attenuates stretch responses and sensitization of mouse colorectal afferents

    PubMed Central

    Feng, Bin; Kiyatkin, Michael E.; La, Jun-Ho; Ge, Pei; Solinga, Robert; Silos-Santiago, Inmaculada; Gebhart, G.F.

    2013-01-01

    Irritable bowel syndrome (IBS) is characterized by altered bowel habits, persistent pain and discomfort, and typically colorectal hypersensitivity. Linaclotide, a peripherally-restricted 14-amino acid peptide approved for the treatment of IBS with constipation, relieves constipation and reduces IBS-associated pain in these patients presumably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic guanosine monophosphate (cGMP) from intestinal epithelial cells. We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primary downstream effector of that activation, cGMP, directly modulates responses and sensitization of mechanosensitive colorectal primary afferents. The distal 2 cm of mouse colorectum with attached pelvic nerve was harvested, pinned flat mucosal side up for in vitro single-fiber recordings and the encoding properties of mechanosensitive afferents (serosal, mucosal, muscular and muscular-mucosal) to probing and circumferential stretch studied. Both cGMP (10–300μM) and uroguanylin (1–1000nM) applied directly to colorectal receptive endings significantly reduced responses of muscular and muscular-mucosal afferents to stretch; serosal and mucosal afferents were not affected. Sensitized responses (i.e., increased responses to stretch) of muscular and muscular-mucosal afferents were reversed by cGMP, returning responses to stretch to control. Blocking the transport of cGMP from colorectal epithelia by probenecid, a mechanism validated by studies in cultured intestinal T84 cells, abolished the inhibitory effect of uroguanylin on muscular-mucosal afferents. These results suggest that GC-C agonists like linaclotide alleviate colorectal pain and hypersensitivity by dampening stretch-sensitive afferent mechanosensitivity and normalizing afferent sensitization. PMID:23739979

  4. Blockade of B2 receptors attenuates the responses of group III afferents to static contraction.

    PubMed

    Leal, Anna K; Stone, Audrey J; Yamauchi, Katsuya; McCord, Jennifer L; Kaufman, Marc P

    2013-10-25

    Recent evidence has been presented demonstrating that group III mechanoreceptors comprise an important part of the sensory arm of the exercise pressor reflex, which in turn functions to increase arterial blood flow to contracting skeletal muscles. Although group III afferents are stimulated by mechanical distortion of their receptive fields, they are also stimulated by bradykinin, which is produced by skeletal muscle when it contracts. Moreover, blockade of B (bradykinin)2 receptors has been shown to decrease the magnitude of the exercise pressor reflex. Nevertheless, the effect of blockade of B2 receptors on responses of group III afferents to contraction is not known. We therefore determined the effect of B2 receptor blockade with HOE 140 (40μg/kg) on the responses to both static and intermittent contraction of group III afferents with endings in the triceps surae muscle of decerebrated unanesthetized cats. We found that HOE 140 significantly attenuated (P=0.04) the responses of 14 group III afferents to static contraction, but did not significantly attenuate (P=0.16) the responses of 16 group III afferents to intermittent contraction. The attenuation induced by HOE 140 was present throughout the static contraction period, and led us to speculate that blockade of B2 receptors on the endings of group III afferents decreased their sensitivity to mechanical events occurring in the working muscles. PMID:24036460

  5. Efferent Control of Hair Cell and Afferent Responses in the Semicircular Canals

    PubMed Central

    Boyle, Richard; Rabbitt, Richard D.; Highstein, Stephen M.

    2009-01-01

    The sensations of sound and motion generated by the inner ear are controlled by the brain through extensive centripetal innervation originating within the brain stem. In the semicircular canals, brain stem efferent neurons make synaptic contacts with mechanosensory hair cells and with the dendrites of afferent neurons. Here, we examine the relative contributions of efferent action on hair cells and afferents. Experiments were performed in vivo in the oyster toadfish, Opsanus tau. The efferent system was activated via electrical pulses to the brain stem and sensory responses to motion stimuli were quantified by simultaneous voltage recording from afferents and intracellular current- and/or voltage-clamp recordings from hair cells. Results showed synaptic inputs to both afferents and hair cells leading to relatively long-latency intracellular signaling responses: excitatory in afferents and inhibitory in hair cells. Generally, the net effect of efferent action was an increase in afferent background discharge and a simultaneous decrease in gain to angular motion stimuli. Inhibition of hair cells was likely the result of a ligand-gated opening of a major basolateral conductance. The reversal potential of the efferent-evoked current was just below the hair cell resting potential, thus resulting in a small hyperpolarization. The onset latency averaged about 90 ms and latency to peak response was 150–400 ms. Hair cell inhibition often outlasted afferent excitation and, in some cases, latched hair cells in the “off” condition for >1 s following cessation of stimulus. These features endow the animal with a powerful means to adjust the sensitivity and dynamic range of motion sensation. PMID:19571186

  6. The innate response to peanut extract in ovine afferent lymph and its correlation with allergen sensitisation.

    PubMed

    Van Gramberg, Jenna L; Bischof, Robert J; O'Hehir, Robyn E; de Veer, Michael J; Meeusen, Els N

    2015-07-01

    The innate response generated after initial allergen exposure is crucial for polarising adaptive immunity, but little is known about how it drives an atopic or type-2 immune response. The present study characterises the response of skin-draining afferent lymph in sheep following injection with peanut (PN) extract in the presence or absence of aluminium hydroxide (AlOH) adjuvant. Lymph was collected and innate cell populations characterised over an 84 h time period. The innate response to PN extract in afferent lymph displayed an early increase in neutrophils and monocytes without any changes in the dendritic cell (DC) population. PN antigen was transported by neutrophils and monocytes for the first 36 h, after which time DCs were the major antigen trafficking cells. AlOH adjuvant gradually increased antigen uptake by DCs at the later time points. Following lymphatic characterisation, sheep were sensitised with PN extract by three subcutaneous injections of PN in AlOH, and the level of PN-specific immunoglobulin E (IgE) was determined. Sheep with higher levels of steady-state DCs in afferent lymph showed increased monocytic recruitment in afferent lymph and reduced PN-specific IgE following sensitisation. In addition, DCs from afferent lymph that had ingested PN antigen increased the expression of monocyte chemoattractant mRNA. The results of this study show that the innate response to PN extract involves a dynamic change in cell populations in the afferent lymph over time. In addition, DCs may determine the strength of the initial inflammatory cell response, which in turn may determine the nature of the antigen-specific adaptive response. PMID:25666095

  7. Purinergic 2 receptor blockade prevents the responses of group IV afferents to post-contraction circulatory occlusion

    PubMed Central

    Kindig, Angela E; Hayes, Shawn G; Kaufman, Marc P

    2007-01-01

    ATP, by activating purinergic 2 (P2) receptors on group III and IV afferents, is thought to evoke the metabolic component of the exercise pressor reflex. Previously we have shown that injection of PPADS, a P2 receptor antagonist, into the arterial supply of skeletal muscle of decerebrated cats attenuated the responses of group III and IV afferents to static contraction while the muscles were freely perfused. We have now tested the hypothesis that injection of PPADS (10 mg kg−1) attenuated the responses of group III (n = 13) and group IV afferents (n = 9) to post-contraction circulatory occlusion. In the present study, we found that PPADS attenuated the group III afferent responses to static contraction during circulatory occlusion (P < 0.05). Likewise, PPADS abolished the group IV afferent responses to static contraction during occlusion (P = 0.001). During a 1 minute period of post-contraction circulatory occlusion, four of the 13 group III afferents and eight of the nine group IV afferents maintained their increased discharge. A Fischer's exact probability test revealed that more group IV afferents than group III afferents were stimulated by post-contraction circulatory occlusion (P < 0.02). In addition, the nine group IV afferents increased their mean discharge rate over baseline levels during the post-contraction circulatory occlusion period, whereas the 13 group III afferents did not (P < 0.05). PPADS abolished this post-contraction increase in discharge by the group IV afferents (P < 0.05). Our findings suggest that P2 receptors on group IV afferents play a role in evoking the metabolic component of the exercise pressor reflex. PMID:17038431

  8. The pupillary light reflex in normal subjects.

    PubMed Central

    Ellis, C J

    1981-01-01

    In 19 normal subjects the pupillary reflex to light was studied over a range of stimulus intensities by infrared electronic pupillography and analysed by a computer technique. Increasing stimulus intensity was associated with an increase in direct light reflex amplitude and maximum rate of constriction and redilatation. Latency from stimulus to onset of response-decreased with increasing stimulus intensity. The normal range for each of these parameters is given and the significance of these results in clinical pupillary assessment discussed. PMID:7326222

  9. Pharmacological Isolation of Cognitive Components Influencing the Pupillary Light Reflex.

    PubMed

    Steinhauer, Stuart R; Condray, Ruth; Pless, Misha L

    2015-01-01

    Cognitive operations can be detected by reduction of the pupillary light response. Neurophysiological pathways mediating this reduction have not been distinguished. We utilized selective blockade of pupillary sphincter or dilator muscles to isolate parasympathetic or sympathetic activity during cognition, without modifying central processes. Pupil diameter was measured during the light reaction in 29 normal adults under three processing levels: No Task, during an easy task (Add 1), or a difficult task (Subtract 7). At three separate sessions, the pupil was treated with placebo, tropicamide (blocking the muscarinic sphincter receptor), or dapiprazole (blocking the adrenergic dilator receptor). With placebo, pupil diameter increased with increasing task difficulty. The light reaction was reduced only in the Subtract 7 condition. Dapiprazole (which decreased overall diameter) showed similar task-related changes in diameter and light reflex as for placebo. Following tropicamide (which increased overall diameter), there was a further increase in diameter only in the difficult task. Findings suggest two separate inhibitory components at the parasympathetic oculomotor center. Changes in baseline diameter are likely related to reticular activation. Inhibition of the light reaction in the difficult task is likely associated with cortical afferents. Sustained sympathetic activity also was present during the difficult task. PMID:26090217

  10. Full-Field Pupillary Light Responses, Luminance Thresholds, and Light Discomfort Thresholds in CEP290 Leber Congenital Amaurosis Patients

    PubMed Central

    Collison, Frederick T.; Park, Jason C.; Fishman, Gerald A.; McAnany, J. Jason; Stone, Edwin M.

    2015-01-01

    Purpose To investigate visual function in patients with CEP290 Leber congenital amaurosis (LCA-CEP290), using three full-field tests that can be performed by patients with poor fixation. Methods Six patients (age range, 9–39 years) with LCA-CEP290 participated in the study. Stimuli for all three tests (full-field stimulus test [FST], pupillometry, and light discomfort threshold [LDT] testing) were generated by the Diagnosys ColorDome ganzfeld, by using achromatic stimuli as well as long- and short-wavelength stimuli to target rod and cone photoreceptors with all three tests and, in the latter two tests, melanopsin photoreceptors. Results Dark-adapted FST thresholds in LCA-CEP290 patients were cone mediated and elevated between 4.8 and 6.2 log units above the normal achromatic threshold. The FST threshold was not measurable in one patient. The rod-mediated transient pupillary light reflex (PLR) was absent in all but the youngest patient, where unreliable responses precluded PLR quantification. Cone-mediated transient PLRs were subnormal in five patients, and absent in another. Sustained melanopsin-mediated PLRs were measurable in all patients. Full-field LDT thresholds were elevated compared to normal controls, and were lower for short-wavelengh than for long-wavelength stimuli. Conclusions The FST thresholds and transient PLRs were cone mediated in our cohort LCA-CEP290 patients. Rod-mediated PLRs were undetectable, whereas melanopsin-mediated sustained responses were detected in all patients, suggesting a relative preservation of inner-retina function. The LDT elevations for the patients are somewhat paradoxical, given their subjective perception of photoaversion. Relative aversion to short-wavelength light suggests influence from melanopsin on LDTs in these patients. PMID:26529047

  11. The effects of a selective 5-HT2 receptor antagonist (ICI 170,809) on platelet aggregation and pupillary responses in healthy volunteers.

    PubMed Central

    Millson, D S; Jessup, C L; Swaisland, A; Haworth, S; Rushton, A; Harry, J D

    1992-01-01

    1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to the pupillary light constrictor response in eight healthy male volunteers. 3. Pupillary dark adapted responses to a 0.5 s light stimulus were measured using a portable infrared pupillometer, for up to 24 h after dosing. 4. The in vitro platelet 5-HT aggregation response was reduced by ICI 170,809, with depression of the dose-response curve to 5-HT at all concentrations of 5-HT and with no evidence for a parallel shift. 5. The ex vivo platelet 5-HT response demonstrated a dose related significant (P less than 0.02) decrease in aggregation reaching a maximum at 2 h after dosing with the effect persisting for at least 8 h after dosing with the 7 and 15 mg doses. 6. Resting pupil diameter (RPD), and light induced pupillary responses in the dark adapted pupil, showed a significant (P less than 0.01) dose related reduction with significant (P less than 0.05) effects still present with the 15 and 30 mg doses at 8 h after dosing. 7. We conclude that, changes in both ex vivo platelet aggregation to 5-HT and dark adapted pupil size, are significantly correlated (P less than 0.0001) with log plasma concentrations (ng ml-1) of ICI 170,809, enabling the assessment of 5-HT2-receptor antagonism in man. PMID:1576048

  12. Pupillary Stroop effects

    PubMed Central

    Ørbo, Marte; Holmlund, Terje; Miozzo, Michele

    2010-01-01

    We recorded the pupil diameters of participants performing the words’ color-naming Stroop task (i.e., naming the color of a word that names a color). Non-color words were used as baseline to firmly establish the effects of semantic relatedness induced by color word distractors. We replicated the classic Stroop effects of color congruency and color incongruency with pupillary diameter recordings: relative to non-color words, pupil diameters increased for color distractors that differed from color responses, while they reduced for color distractors that were identical to color responses. Analyses of the time courses of pupil responses revealed further differences between color-congruent and color-incongruent distractors, with the latter inducing a steep increase of pupil size and the former a relatively lower increase. Consistent with previous findings that have demonstrated that pupil size increases as task demands rise, the present results indicate that pupillometry is a robust measure of Stroop interference, and it represents a valuable addition to the cognitive scientist’s toolbox. PMID:20865297

  13. Afferent lymphatic cannulation as a model system to study innate immune responses to infection and vaccination.

    PubMed

    Neeland, Melanie R; Meeusen, Els N T; de Veer, Michael J

    2014-03-15

    The afferent lymphatics consist of the cells and immunomodulatory signals that are involved in the early response to peripheral stimuli. Examination of this compartment in both homeostatic and stimulatory conditions permits the analysis of the innate biological pathways responsible for the generation of an adaptive immune response in the lymph node. Afferent lymphatic cannulation is therefore an ideal model system to study cellular migration and antigen dispersal kinetics during infection and vaccination. Utilisation of these lymphatic cannulation models has demonstrated the ability to both increase current understanding of infectious diseases, vaccine delivery systems and has the potential to target effector cells and molecules that may be used as novel therapeutic or vaccine targets. PMID:23369582

  14. The pupillary response discriminates between subjective and objective familiarity and novelty

    PubMed Central

    Montaldi, Daniela

    2015-01-01

    Abstract The pupil response discriminates between old and new stimuli, with old stimuli characterized by larger pupil dilation patterns than new stimuli. We sought to explore the cause of the pupil old/new effect and discount the effect of targetness, effort, recollection retrieval, and complexity of the recognition decision. Two experiments are reported in which the pupil response and the eye fixation patterns were measured, while participants identified novel and familiar object stimuli, in two separate tasks, emphasizing either novelty or familiarity detection. In Experiment 1, familiarity and novelty decisions were taken using a rating scale, while in Experiment 2 a simpler yes/no decision was used. In both experiments, we found that detection of target familiar stimuli resulted in greater pupil dilation than the detection of target novel stimuli, while the duration of the first fixation discriminated between familiar and novel stimuli as early as within 320 ms after stimulus onset. Importantly, the pupil response distinguished between the objective (during an earlier temporal component) and the subjective (during a later temporal component) status of the stimulus for misses and false alarms. In the light of previous findings, we suggest that the pupil and fixation old/new effects reflect the distinct neural and cognitive mechanisms involved in the familiarity and novelty decisions. The findings also have important implications for the use of pupil dilation and eye movement patterns to explore explicit and implicit memory processes. PMID:26174940

  15. Responses in muscle afferent fibres of slow conduction velocity to contractions and ischaemia in the cat.

    PubMed Central

    Mense, S; Stahnke, M

    1983-01-01

    The aim of the study was to find out to what extent muscle receptors with slowly conducting afferent fibres (group III and IV) are activated by muscular contractions of moderate force, and what kind of muscle afferents could mediate the pain of ischaemic exercise. In chloralose-anaesthetized cats, the impulse activity of single afferent units from the triceps surae muscle was recorded from dorsal root filaments during muscular contractions with intact blood supply and after occlusion of the muscle artery. Two types of responses were observed to contractions without muscular ischaemia. One was characterized by sudden onset and a graded response amplitude to contractions of increasing force. In most cases stretching the muscle was also an effective stimulus. Units showing this response behaviour were labelled c.s.m (contraction-sensitive with mechanical mechanism of activation). The other response type had a more delayed onset and often outlasted the exercise period; because of the unknown mechanism of activation, units of this kind were labelled c.s.x. The proportion of c.s.m receptors was significantly higher amongst group III than amongst group IV units. During ischaemic contractions of comparable force the c.s.m and c.s.x receptors exhibited an unchanged or a decreased response amplitude. Under these conditions another receptor type (N, for nociceptive) was activated which did not respond to contractions with intact blood supply. Vigorous activations during ischaemic work were only observed in group IV receptors. The majority of the 131 group III and IV units tested did not respond to contractions at all. These contraction-insensitive (c.i.) endings probably comprised different receptor populations (nociceptors, thermoreceptors, low-threshold mechanoreceptors). It is concluded that the various central nervous effects of muscular exercise without ischaemia which are known to be due to raised activity in thin muscle afferents (e.g. cardiopulmonary adjustments

  16. 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

  17. 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.

  18. Characterization and modeling of P-type electrosensory afferent responses to amplitude modulations in a wave-type electric fish.

    PubMed

    Nelson, M E; Xu, Z; Payne, J R

    1997-11-01

    The first stage of information processing in the electrosensory system involves the encoding of local changes in transdermal potential into trains of action potentials in primary electrosensory afferent nerve fibers. To develop a quantitative model of this encoding process for P-type (probability-coding) afferent fibers in the weakly electric fish Apteronotus leptorhynchus, we recorded single unit activity from electrosensory afferent axons in the posterior branch of the anterior lateral line nerve and analyzed responses to electronically generated sinusoidal amplitude modulations of the local transdermal potential. Over a range of AM frequencies from 0.1 to 200 Hz, the modulation transfer function of P-type afferents is high-pass in character, with a gain that increases monotonically up to AM frequencies of 100 Hz where it begins to roll off, and a phase advance with a range of 15-60 degrees. Based on quantitative analysis of the observed gain and phase characteristics, we present a computationally efficient model of P-type afferent response dynamics which accurately characterizes changes in afferent firing rate in response to amplitude modulations of the fish's own electric organ discharge over a wide range of AM frequencies relevant to active electrolocation. PMID:9373958

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

    SciTech Connect

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    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 often 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 prostaglandin

  20. Cortical Responses to Aδ-Fiber Stimulation: Magnetoencephalographic Recordings in a Subject Lacking Large Myelinated Afferents

    PubMed Central

    Olausson, Håkan; Cole, Jonathan; Jousmäki, Veikko; Hari, Riitta

    2010-01-01

    Controversy persists over the role of the primary somatosensory cortex (SI) in processing small-fiber peripheral afferent input. We therefore examined subject I.W, who, due to sensory neuronopathy syndrome, has no large-fiber afferents below C3 level. Cortical evoked responses were recorded with a whole-scalp neuromagnetometer to high-intensity electrical stimulation of the distal right radial, median, and tibial nerves and skin over the forearm and mechanical stimulation of (neurologically intact) lip. The responses to electrical stimulation in the Aβ-denervated limbs peaked at 110–140 ms in contralateral SI and at 140–220 ms in contralateral secondary somatosensory cortex (SII), consistent with Aδ-mediated input. I.W. was able to localize pin-prick stimuli with 4 cm accuracy. Responses to laser stimuli on the radial dorsum of the hand peaked in contralateral SII cortex at 215 ms, also compatible with Aδ-mediated input. These results support the role of the SI cortex in processing the sensory discriminative aspects of Aδ-mediated input. PMID:19959562

  1. Possible role of afferent autonomic signals in abdominal organs in anorexic and cardiovascular responses to nicotine injection in rats.

    PubMed

    Yagi, Shintaro; Tanida, Mamoru; Satomi, Jun

    2015-05-27

    Smoking generally causes an increase in nicotine levels in the blood, affecting the brain components, such as the hypothalamus (feeding-related area) or the brain stem (cardiovascular control area). In terms of nicotine transmission to the brain, a new insight that the afferent vagal nerve in the liver is important for sensing increased nicotine levels in the blood and informing the brain was reported in an experiment with rats. However, it has not been clarified whether the afferent autonomic nerve system is implicated in feeding and cardiovascular responses to nicotine. Here, we examined the possible role of afferent autonomic nerve transmission in rats in regulating feeding behavior and cardiovascular functions by nicotine. An intravenous injection of nicotine dose dependently increased the blood pressure (BP) in urethane-anesthetized rats; high nicotine doses also led to an increase in BP in conscious rats. Further, an intravenous injection of nicotine for 3 days reduced food intake and body weight gain in rats. The weight-reducing action of intravenous nicotine was abolished by blocking the afferent sympathetic signals in the abdominal organs, but not the vagal nerve signals. Moreover, the hypertensive action of nicotine was not abolished either by afferent sympathectomy or by vagotomy. Thus, these data suggest that nicotine injected into the vein acts on the afferent sympathetic nerve in the abdominal organs and transmits signals to the brain for reducing body weight, but not for suppressing appetite or increasing BP. PMID:25875474

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

    PubMed

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho

    2015-01-01

    Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 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 PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 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 PGE2 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 prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis. PMID:25446121

  3. Pupillary correlates of lapses of sustained attention.

    PubMed

    Unsworth, Nash; Robison, Matthew K

    2016-08-01

    The current study examined the extent to which pupillary responses (both pretrial baseline and phasic responses) would accurately track lapses of attention as predicted by theories of locus coeruleus norepinephrine (LC-NE) functioning. Participants performed a sustained attention task while pupil responses were continuously recorded. Periodically during the task, participants were presented with thought probes to determine if they were on or off task. The results suggested the pupillary responses accurately distinguished on from off-task states. Importantly, pretrial baseline pupil responses distinguished different types of lapses of attention, with inattentive and mind-wandering states being associated with small pretrial baseline pupil diameters on average and distracted states being associated with larger pretrial baseline pupil diameters on average compared to focused states. These results support the notion that pupil diameter is sensitive to different types of lapses of attention which may be associated with different LC-NE modes. PMID:27038165

  4. Determinants of renal microvascular response to ACh: afferent and efferent arteriolar actions of EDHF.

    PubMed

    Wang, Xuemei; Loutzenhiser, Rodger

    2002-01-01

    The renal microvascular actions of ACh were investigated using the in vitro perfused hydronephrotic rat kidney. ACh reversed ANG II-induced vasoconstriction in the afferent and efferent arteriole by 106 +/- 2 and 75 +/- 5%, respectively. Inhibition of nitric oxide synthase [NOS; 100 micromol/l N(G)-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (COX; 10 micromol/l ibuprofen) prevented the sustained response of the afferent arteriole but did not reduce the magnitude of the initial dilation (97 +/- 7%). However, NOS/COX inhibition abolished the response of the efferent arteriole. The underlying mechanisms mediating this endothelium-derived hyperpolarizing factor (EDHF)-like response were characterized using K channel blockers. Ba (100 micromol/l), tetraethylammonium (1 mmol/l), and ouabain (3 mmol/l) had no effect, arguing against a role of an inward rectifier K channel, large-conductance Ca-activated K channel, or Na,K-ATPase. Charybdotoxin (10 nmol/l) and apamin (1.0micromol/l) attenuated the response when administered alone (63 +/- 7% and 37 +/- 5%, respectively) and abolished the response when coadministered (0.1 +/- 1.0%). These findings indicate that, as in other vascular beds, the renal EDHF-like response to ACh involves K channels that are sensitive to a combination of apamin and charybdotoxin. Our finding that EDHF modulates preglomerular, but not postglomerular, tone is consistent with the evolving concept that vasomotor mechanisms in cortical efferent arterioles do not involve voltage-gated Ca entry. PMID:11739120

  5. Integrated phrenic responses to carotid afferent stimulation in adult rats following perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1997-01-01

    1. Hypoxic ventilatory responses are greatly attenuated in adult rats exposed to moderate hyperoxia (60% O2) during the first month of life (perinatal treated rats). The present study was designed to test the hypothesis that perinatal hyperoxia impairs central integration of carotid chemoreceptor afferent inputs, thereby diminishing the hypoxic ventilatory response. 2. Time-dependent phrenic nerve responses to electrical stimulation of the carotid sinus nerve (CSN) and steady-state relationships between CSN stimulation frequency and phrenic nerve output were compared in control and perinatal treated rats. The rats were urethane anaesthetized, vagotomized, paralysed and artificially ventilated. End-tidal CO2 was monitored and maintained at isocapnic levels; arterial blood gases were determined. 3. Two stimulation protocols were used: (1) three 2 min episodes of CSN stimulation (20 Hz, 0.2 ms duration, 3 x threshold), separated by 5 min intervals; and (2) nine 45 s episodes of CSN stimulation with stimulus frequencies ranging from 0.5 to 20 Hz (0.2 ms duration, 3 x threshold), separated by 4 min intervals. 4. The mean threshold currents to elicit phrenic responses were similar between groups. Burst frequency (f, burst min-1), peak amplitude of integrated phrenic activity (integral of Phr), and minute phrenic activity (integral of Phr x f) during and after CSN stimulation were not distinguishable between groups in either protocol at any time or at any stimulus intensity (P > 0.05). 5. Perinatal hyperoxia does not alter temporal or steady-state phrenic responses to CSN stimulation, suggesting that the central integration of carotid chemoreceptor afferent inputs is not impaired in perinatal treated rats. It is speculated that carotid chemoreceptors per se are impaired in perinatal treated rats. PMID:9161991

  6. Pupillary responses during a joint attention task are associated with nonverbal cognitive abilities and sub-clinical symptoms of autism

    PubMed Central

    Erstenyuk, Valentyna; Swanson, Meghan R.; Siller, Michael

    2015-01-01

    Measures of pupillary dilation provide a temporally sensitive, quantitative indicator of cognitive resource allocation. The current study included 39 typically developing children between 3 and 9 years of age. Children completed a free-viewing task designed to elicit gaze following, a core deficit of Autism Spectrum Disorders (ASD). Results revealed a negative association between children's pupil dilation and a standardized measure of nonverbal intelligence, suggesting that children with lower intelligence allocated more cognitive resources than children with higher intelligence. In addition, the results revealed a negative association between pupil dilation and a parent-report measure of sub-clinical symptoms of ASD, suggesting that children with fewer ASD-related symptoms allocated more cognitive resources than children who showed more sub-clinical symptoms of ASD. Both associations were independent of each other and could not be explained by variation in chronological age. These findings extend previous research demonstrating associations between basic aspects of visual processing and intelligence. In addition, these findings comport with recent theories of ASD that emphasize reduced sensitivity to the reward value of social situations. When confronted with social ambiguity, children with more ASD-related symptoms allocated fewer cognitive resources to resolving this ambiguity than children who showed fewer sub-clinical symptoms of ASD. PMID:25821516

  7. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion

    PubMed Central

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2015-01-01

    Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia. PMID:26441669

  8. Calcium dynamics underlying the myogenic response of the renal afferent arteriole

    PubMed Central

    Edwards, Aurélie

    2013-01-01

    The renal afferent arteriole reacts to an elevation in blood pressure with an increase in muscle tone and a decrease in luminal diameter. This effect, known as the myogenic response, is believed to stabilize glomerular filtration and to protect the glomerulus from systolic blood pressure increases, especially in hypertension. To study the mechanisms underlying the myogenic response, we developed a mathematical model of intracellular Ca2+ signaling in an afferent arteriole smooth muscle cell. The model represents detailed transmembrane ionic transport, intracellular Ca2+ dynamics, the kinetics of myosin light chain phosphorylation, and the mechanical behavior of the cell. It assumes that the myogenic response is initiated by pressure-induced changes in the activity of nonselective cation channels. Our model predicts spontaneous vasomotion at physiological luminal pressures and KCl- and diltiazem-induced diameter changes comparable to experimental findings. The time-periodic oscillations stem from the dynamic exchange of Ca2+ between the cytosol and the sarcoplasmic reticulum, coupled to the stimulation of Ca2+-activated potassium (KCa) and chloride (ClCa) channels, and the modulation of voltage-activated L-type channels; blocking sarco/endoplasmic reticulum Ca2+ pumps, ryanodine receptors (RyR), KCa, ClCa, or L-type channels abolishes these oscillations. Our results indicate that the profile of the myogenic response is also strongly dependent on the conductance of ClCa and L-type channels, as well as the activity of plasmalemmal Ca2+ pumps. Furthermore, inhibition of KCa is not necessary to induce myogenic contraction. Lastly, our model suggests that the kinetic behavior of L-type channels results in myogenic kinetics that are substantially faster during constriction than during dilation, consistent with in vitro observations (Loutzenhiser R, Bidani A, Chilton L. Circ. Res. 90: 1316–1324, 2002). PMID:24173354

  9. The responses of primary spindle afferents to fusimotor stimulation at constant and abruptly changing rates.

    PubMed Central

    Hulliger, M

    1979-01-01

    1. Single fusimotor fibres to de-efferented soleus of the cat were stimulated to investigate the size and time course of the responses elicited in single primary spindle afferents. The muscle was kept at constant length close to the physiological maximum. Constant and alternating rates of fusimotor stimulation were used: (a) repetitive stimulation at constant rate (maintained stimulation); (b) modulated stimulation with the rate of activation alternating between two constant levels at repeat frequencies between 0.09 and 2 Hz (rectangular stimulation). The responses were averaged and displayed as post-stimulus time (pst) histograms (a) or as cycle histograms (b). 2. During static fusimotor stimulation the pst histograms could be clearly modulated over a range of rates of stimulation. However, histogram modulation was not a prerequisite of static action since with different fibres the degree of modulation could range from deeply modulated to completely non-modulated to completely non-modulated. 3. Dynamic fusimotor stimulation was almost always accompanied by non-modulated pst histograms. 4. Primary spindle afferents responded to rectangular stimulation of either kind of fusimotor fibre with an approximately rectangular modulation of the rate of discharge. At the repeat frequencies studied the size of the responses was appreciably larger with static than with dynamic activation. It was assessed as 'fusimotor rate-sensitivity during alternating stimulation' by the response/stimulus ratio which is defined as change in firing/change in alternating rate of stimulation, in impulses/stimuli. The mean values of rate-sensitivity were 1.35 impulses/stimuli (statics) and 0.29 (dynamics), with a static/dynamic ratio of 4.7. 5. The afferents' 'fusimotor rate-sensitivity during steady stimulation' (change in firing/change in maintained rate of stimulation( was also determined. The mean values were 0.78 (static) and 0.37 (dynamics), with a static/dynamic ratio of 2.1. 6. The time

  10. Endogenously produced 20-HETE modulates myogenic and TGF response in microperfused afferent arterioles.

    PubMed

    Ge, Ying; Murphy, Sydney R; Lu, Yan; Falck, John; Liu, Ruisheng; Roman, Richard J

    2013-01-01

    Previous studies have indicated that 20-hydroxyeicosatetraeonic acid (20-HETE) modulates vascular tone in large cerebral and renal arteries through inhibition of the large conductance, calcium sensitive potassium (BK) channel activity. However, the role of 20-HETE in modulating tubuloglomerular feedback (TGF) and the myogenic response in the afferent arteriole (Af-Art) is unknown. The present study examined the effects of inhibitors of the synthesis and action of 20-HETE on the myogenic and TGF responses of isolated rabbit and mouse Af-Arts. Luminal diameter decreased by 9.2±0.5% in mice and 8.9±1.3% in rabbit Af-Art when the perfusion pressure was increased from 60 to 120 mmHg. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), or a selective 20-HETE antagonist, 6, 15-20-hydroxyeicosadienoic acid (6, 15-20-HEDE, 10 μM) completely blocked the myogenic response of both rabbit and mouse Af-Art, while addition of 5, 14-20-HEDE (10 μM), a 20-HETE agonist, restored the myogenic response in vessels treated with HET0016. Increases in NaCl concentration from 10 to 80 mM of the solution perfusing the macula densa constricted the Af-Art of rabbits by 6.0±1.4 μm (n=5). Addition of a 20-HETE agonist to the tubular perfusate potentiated the TGF-mediated vasoconstrictor response. This response was blocked by addition of a 20-HETE antagonist (6, 15-20-HEDE, 10 μM) to the vascular perfusate. These studies indicate that locally produced 20-HETE plays an important role in modulating the myogenic and TGF responsiveness of the Af-Art and may help explain how deficiencies in the renal formation of 20-HETE could promote the development of hypertension induced glomerular injury. PMID:23500064

  11. The effects of a 5-HT2 receptor antagonist (ICI 169,369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers.

    PubMed Central

    Millson, D S; Haworth, S J; Rushton, A; Wilkinson, D; Hobson, S; Harry, J

    1991-01-01

    1. ICI 169,369 (2-(2-dimethylamino ethylthio)-3-phenyl quinoline) is a potent selective competitive antagonist of the 5-HT2 receptor in animal models. Effects of ICI 169,369 as single oral doses (80 and 120 mg) separated by 1 week, on the power spectrum of waking EEG, dark adapted pupil responses and sedation score, were studied in a double-blind, placebo controlled, randomised cross over within subject comparison, in six healthy male volunteers. 2. Pupillary responses were measured using a portable infrared pupillometer following 15 min dark adaptation, assessing resting vertical pupil diameter (RPD), light constricted diameter (MPD) and recovered final diameter (FPD) at the end of a 3 s measurement cycle. 3. Both doses of ICI 169,369 produced a mean 36% (range 10-54%) decrease in log 10 power of the waking EEG alpha activity with eyes closed (P less than 0.02), and mean 38% (range 2-86%) increase in theta activity at 2 h compared with placebo. 4. Both 80 and 120 mg doses of ICI 169,369 reduced RPD by approximately 30% from a predose value of 6.25 mm (+/- 0.87; 95% CI) and from placebo values 6.41 mm (+/- 1.06) and 7.48 mm (+/- 1.49) at 3 and 5 h after dosing. MPD was reduced by 50% with the 120 mg dose at 5 h after dosing (placebo 5.2 mm; ICI 169,369 2.7 mm; P less than 0.05). FPD was significantly reduced (P less than 0.01) by both doses at 3 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1958438

  12. 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

  13. Responses of the frog primary vestibular afferents to direct vibration of the semicircular canal

    NASA Technical Reports Server (NTRS)

    Orlov, I. V.

    1980-01-01

    Responses of primary afferents (PA) of lateral semicircular canal to sinusoidal vibration of the canal wall within the range 0.05-200 Hz (mean amplitudes 5-15 microns) in immobilized frogs were studied. Dynamic characteristics (gain, phase) of relative linear velocity of the vibrator (micron X/s) were examined. At 0.2 Hz, the gain was 5.35 + or - 3.19 imp X/s /micron X/s (mean; S.D.; n=14) and linearly decreased if the frequency rose. Phase lag of relative velocity at 0.05 Hz was 49.8 deg + or - 16.5 deg (n=13) and at 1 Hz 97 deg + or - 9.4 deg (n=22). At 100 Hz phase lag was about 240 deg. Three groups of PA are described: wide range PA reacting in the range from 0.05 up to 60-180 Hz; high frequency PA responding in the range from 20-40 up to 100-150 Hz; and low frequency PA responding in the range from 0.05 up to 2-20 Hz.

  14. Bilateral persistent pupillary membranes associated with cataract

    PubMed Central

    Ahmad, Syed Shoeb; Binson, Caroline; Lung, Chong Ka; Ghani, Shuaibah Abdul

    2011-01-01

    Summary Exuberant persistent pupillary membranes (PPM) are rare in adult eyes. We report the case of a 53-year-old man diagnosed with bilateral, profuse, persistent pupillary membranes and unilateral cataract. PMID:23362401

  15. Intrasaccadic perception triggers pupillary constriction.

    PubMed

    Mathôt, Sebastiaan; Melmi, Jean-Baptiste; Castet, Eric

    2015-01-01

    It is commonly believed that vision is impaired during saccadic eye movements. However, here we report that some visual stimuli are clearly visible during saccades, and trigger a constriction of the eye's pupil. Participants viewed sinusoid gratings that changed polarity 150 times per second (every 6.67 ms). At this rate of flicker, the gratings were perceived as homogeneous surfaces while participants fixated. However, the flickering gratings contained ambiguous motion: rightward and leftward motion for vertical gratings; upward and downward motion for horizontal gratings. When participants made a saccade perpendicular to the gratings' orientation (e.g., a leftward saccade for a vertical grating), the eye's peak velocity matched the gratings' motion. As a result, the retinal image was approximately stable for a brief moment during the saccade, and this gave rise to an intrasaccadic percept: A normally invisible stimulus became visible when eye velocity was maximal. Our results confirm and extend previous studies by demonstrating intrasaccadic perception using a reflexive measure (pupillometry) that does not rely on subjective report. Our results further show that intrasaccadic perception affects all stages of visual processing, from the pupillary response to visual awareness. PMID:26339536

  16. Pseudophakic pupillary-block glaucoma.

    PubMed Central

    Werner, D.; Kaback, M.

    1977-01-01

    Four cases of iris-supported pseudophakic pupillary-block glaucoma were presented. Pupillary-block glaucoma is the first postoperative complication seen following the implantation of an intraocular lens, and in our series occurred at an incidence of 3-8%. A short review was made of pupillary-block glaucoma with all types of intraocular lenses, with emphasis on the iris-supported lens. The role of inflammation, haemorrhage, and vitreous and lens material in obstructing aqueous flow at the pupil and peripheral iridectomy site was emphasised. Pitfalls in the diagnosis and management of this condition were reviewed. Methods of prevention and treatment were reviewed with emphasis on early mydriasis, along with carbonic anhydrase inhibitors and hyperosmotic agents as a primary medical treatment. Iridectomy, laser iridotomy, or transfixation of the iris was mentioned as a surgical treatment. PMID:871462

  17. Cooling reduces the cutaneous afferent firing response to vibratory stimuli in glabrous skin of the human foot sole.

    PubMed

    Lowrey, Catherine R; Strzalkowski, Nicholas D J; Bent, Leah R

    2013-02-01

    Skin on the foot sole plays an important role in postural control. Cooling the skin of the foot is often used to induce anesthesia to determine the role of skin in motor and balance control. The effect of cooling on the four classes of mechanoreceptor in the skin is largely unknown, and thus the aim of the present study was to characterize the effects of cooling on individual skin receptors in the foot sole. Such insight will better isolate individual receptor contributions to balance control. Using microneurography, we recorded 39 single nerve afferents innervating mechanoreceptors in the skin of the foot sole in humans. Afferents were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration was compared before and after cooling of the receptive field (2-20 min). Overall, firing response was abolished in 30% of all receptors, and this was equally distributed across receptor type (P = 0.69). Longer cooling times were more likely to reduce firing response below 50% of baseline; however, some afferent responses were abolished with shorter cooling times (2-5 min). Skin temperature was not a reliable indicator of the level of receptor activation and often became uncoupled from receptor response levels, suggesting caution in the use of this parameter as an indicator of anesthesia. When cooled, receptors preferentially coded lower frequencies in response to vibration. In response to a sustained indentation, SA receptors responded more like FA receptors, primarily coding "on-off" events. PMID:23155170

  18. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep.

    PubMed Central

    Giussani, D A; Spencer, J A; Moore, P J; Bennet, L; Hanson, M A

    1993-01-01

    afferent limb of this reflex. The bradycardia is mediated through a muscarinic pathway, as it is blocked by atropine. The femoral vasoconstriction is mediated through an alpha-adrenergic mechanism, mediated both neurally by a carotid chemoreflex and via catecholamines released directly from the adrenal medulla. Both these components are blocked by phentolamine. 7. The differences in survival between intact and denervated fetuses during hypoxia after phentolamine suggest that the carotid chemoreflex response to hypoxia involves mechanisms in addition to vagal efferents to the heart and alpha-adrenergic actions at peripheral blood vessels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8350271

  19. On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

    PubMed Central

    Amann, Markus; Runnels, Sean; Morgan, David E; Trinity, Joel D; Fjeldstad, Anette S; Wray, D Walter; Reese, Van R; Richardson, Russell S

    2011-01-01

    Abstract We investigated the role of skeletal muscle afferent feedback in circulatory control during rhythmic exercise in humans. Nine healthy males performed single leg knee-extensor exercise (15/30/45 watts, 3 min each) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. Cardiac output and femoral blood flow were determined, and femoral arterial/venous blood samples were collected during the final minute of each workload. To rule out cephalad migration of fentanyl to the brainstem, we documented unchanged resting ventilatory responses to different levels of hypercapnia. There were no haemodynamic differences between conditions at rest. However, during exercise cardiac output was ∼20% lower with fentanyl blockade compared to control (P < 0.05), secondary to a 6% and 13% reduction in heart rate and stroke volume, respectively. Throughout exercise mean arterial pressure (MAP) was reduced by 7% (P < 0.01) which is likely to have contributed to the 15% fall in femoral blood flow. However, MAP was not completely responsible for this peripheral haemodynamic change as vascular conductance was also attenuated (∼9%). Evidence of increasing noradrenaline spillover (P = 0.09) implicated an elevation in sympathetic outflow in this response. The attenuated femoral blood flow during exercise with fentanyl was associated with a 17% reduction in leg O2 delivery (P < 0.01) and a concomitant rise in the arteriovenous O2 difference (4–9%), but leg O2 consumption remained 7–13% lower than control (P < 0.05). Our findings reveal an essential contribution of continuous muscle afferent feedback to ensure the appropriate haemodynamic and ultimately metabolic response to rhythmic exercise in humans. PMID:21646407

  20. Ventromedial hypothalamic expression of Bdnf is required to establish normal patterns of afferent GABAergic connectivity and responses to hypoglycemia

    PubMed Central

    Kamitakahara, Anna; Xu, Baoji; Simerly, Richard

    2015-01-01

    Objective The ventromedial nucleus of the hypothalamus (VMH) controls energy and glucose homeostasis through direct connections to a distributed network of nuclei in the hypothalamus, midbrain, and hindbrain. Structural changes in VMH circuit morphology have the potential to alter VMH function throughout life, however, molecular signals responsible for specifying its neural connections are not fully defined. The VMH contains a high density of neurons that express brain-derived neurotrophic factor (BDNF), a potent neurodevelopmental effector known to regulate neuronal survival, growth, differentiation, and connectivity in a number of neural systems. In the current study, we examined whether BDNF impacts the afferent and efferent connections of the VMH, as well as energy homeostatic function. Methods To determine if BDNF is required for VMH circuit formation, a transgenic mouse model was used to conditionally delete Bdnf from steroidogenic factor 1 (SF1) expressing neurons of the VMH prior to the onset of establishing neural connections with other regions. Projections of SF1 expressing neurons were visualized with a genetically targeted fluorescent label and immunofluorescence was used to measure the density of afferents to SF1 neurons in the absence of BDNF. Physiological changes in body weight and circulating blood glucose were also evaluated in the mutant mice. Results Our findings suggest that BDNF is required to establish normal densities of GABAergic afferents onto SF1 neurons located in the ventrolateral part of the VMH. Furthermore, loss of BDNF from VMH SF1 neurons results in impaired physiological responses to insulin-induced hypoglycemia. Conclusion The results of this study indicate that BDNF is required for formation and/or maintenance of inhibitory inputs to SF1 neurons, with enduring effects on glycemic control. PMID:26909317

  1. Determinants of renal afferent arteriolar actions of bradykinin: evidence that multiple pathways mediate responses attributed to EDHF.

    PubMed

    Wang, Xuemei; Trottier, Greg; Loutzenhiser, Rodger

    2003-09-01

    The determinants of bradykinin (BK)-induced afferent arteriolar vasodilation were investigated in the in vitro perfused hydronephrotic rat kidney. BK elicited a concentration-dependent vasodilation of afferent arterioles that had been preconstricted with ANG II (0.1 nmol/l), but this dilation was transient in character. Pretreatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (100 micromol/l) and the cyclooxygenase inhibitor ibuprofen (10 micromol/l) did not prevent this dilation when tone was established by ANG II but fully blocked the response when tone was established by elevated extracellular KCl, which suggests roles for both NO and endothelium-derived hyperpolarizing factor (EDHF). We had previously shown that the EDHF-like response of the afferent arteriole evoked by ACh was fully abolished by a combination of charybdotoxin (ChTX;10 nmol/l) and apamin (AP; 1 micromol/l). However, in the current study, treatment with ChTX plus AP only reduced the EDHF-like component of the BK response from 98 +/- 5 to 53 +/- 6% dilation. Tetraethylammonium (TEA; 1 mmol/l), which had no effect on the EDHF-induced vasodilation associated with ACh, reduced the EDHF-like response to BK to 88 +/- 3% dilation. However, the combination of TEA plus ChTX plus AP abolished the response (0.3 +/- 1% dilation). Similarly, 17-octadecynoic acid (17-ODYA) did not prevent the dilation when it was administered alone (77 +/- 9% dilation) but fully abolished the EDHF-like response when added in combination with ChTX plus AP (-0.5 +/- 4% dilation). These findings suggest that BK acts via multiple EDHFs: one that is similar to that evoked by ACh in that it is blocked by ChTX plus AP, and a second that is blocked by either TEA or 17-ODYA. Our finding that a component of the BK response is sensitive to TEA and 17-ODYA is consistent with previous suggestions that the EDHF released by BK is an epoxyeicosatrienoic acid. PMID:12734100

  2. Assessment of pupillary light reflex using a smartphone application

    PubMed Central

    Shin, Young Duck; Bae, Jin Ho; Kwon, Eun Jung; Kim, Hyeon Tae; Lee, Tae-Soo; Choi, Young Jin

    2016-01-01

    In unconscious patients, pupillary light reflex is an indicator of brain damage. In the current study, a smartphone application was developed for the purpose of measuring pupillary light reflex with an aim to determine the agreement between pupillary light reflex measurements using a smartphone application (APP) and a penlight (PEN). The APP acquires five sequential photographs using the camera flash in order to stimulate the pupil. The initial image is captured prior to the flash, and the subsequent image is obtained while the flash is on. The remaining three images are captured whilst the flash is off. Pupillary right reflex was assessed in 30 healthy subjects using a PEN. After 10 min, the examiners inspected the images of light reflex acquired from the same subjects using the APP, and completed the corresponding questionnaire containing details of pupil size and degree of response. Agreement between the two assessment methods was determined by calculating bias, limits of agreement, and the intraclass correlation (ICC) coefficient. A statistically significant difference was not observed between the two methods regarding pupil size and degree of response. Bias was 0.1 mm and limits of agreement were ±1.5 mm, as compared with PEN. ICC was 0.93 (95% confidence interval, 0.89–0.96). Therefore, it may be concluded that the results of pupillary light reflex assessed by PEN and APP display no significant difference. Furthermore, the APP provides advantages such as portability, objectivity and the possibility of being used as objective medical evidence. PMID:27446266

  3. Signal transmission from motor axons to group Ia muscle spindle afferents: frequency responses and second-order non-linearities.

    PubMed

    Windhorst, U; Kokkoroyiannis, T; Laouris, Y; Meyer-Lohmann, J

    1994-03-01

    Spinal recurrent inhibition via Renshaw cells and proprioceptive feedback via skeletal muscle and muscle spindle afferents have been hypothesized to constitute a compound feedback system [Windhorst (1989) Afferent Control of Posture and Locomotion; Windhorst (1993) Robots and Biological Systems--Towards a New Bionics]. To assess their detailed functions, it is necessary to know their dynamic characteristics. Previously we have extensively described the properties of signal transmission from motor axons to Renshaw cells using random motor axon stimulation and data analysis methods based thereupon. Using the same methods, we here compare these properties, in the cat, with those between motor axons and group Ia muscle spindle afferents in terms of frequency responses and nonlinear features. The frequency responses depend on the mean rate (carrier rate) of activation of motor axons and on the strength of coupling between motor units and spindles. In general, they are those of a second-order low-pass system with a cut-off at fairly low frequencies. This contrasts with the dynamics of motor axon-Renshaw cell couplings which are those of a much broader band-pass with its peak in the range of c. 2-15 Hz [Christakos (1987) Neuroscience 23, 613-623]. The second-order non-linearities in motor unit-muscle spindle signal lines are much more diverse than those in motor axon-Renshaw cell couplings. Although the average strength of response declines with mean stimulus rate in both subsystems, there is no systematic relationship between the amount of non-linearity and the average response in the former, whilst there is in the latter. The qualitative appearance of motor unit-muscle spindle non-linearities was complicated as was the average response to motor unit twitches. Thus, whilst Renshaw cells appear to dynamically reflect motor output rather faithfully, muscle spindles seem to signal local muscle fibre length changes and their dynamics. This would be consistent with the

  4. The effect of deep tissue incision on pH responses of afferent fibers and dorsal root ganglia innervating muscle

    PubMed Central

    Kido, Kanta; Gautam, Mamta; Benson, Christopher J.; Gu, He; Brennan, Timothy J.

    2014-01-01

    Background Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis (FDB) muscle-nerve preparation and patch-clamp recordings from cultured dorsal root ganglia (DRG) neurons innervating incised and unincised muscle, we investigated responses to various pH changes. Methods Incision including the plantar FDB muscle or sham operation was made in the rat hindpaw. On postoperative day one, in vitro single fiber recording was undertaken. Based on previous studies, we recorded from at least 40 fibers per group. Also Di-I labeled DRG innervating muscle from rats undergoing incision and a sham operation were cultured and tested for acid responses using whole cell patch-clamp recordings. Results The prevalence of responsive group IV afferents to lactic acid pH 6.5 in the incision group (15 of 67, 22.3%) was greater than that in the control group (2 of 35, 5.7%, p=0.022). In DRG neurons innervating muscle, incision increased mean current amplitudes of acid-evoked currents; the acid-sensing ion channel blocker, amiloride 300 μM, inhibited more than 75% of the acid-evoked current, whereas the transient receptor vanilloid receptor 1 blocker (AMG9810 1 μM) did not cause significant inhibition. Conclusion Our experiments demonstrated that incision increases the responses of FDB muscle afferent fibers to weak acid solutions, and increased acid-evoked currents in DRG innervating muscle. Our data suggest that upregulation of acid-sensing ion channels might underlie this increased chemosensitivity caused by surgery. PMID:23732174

  5. Attention to bright surfaces enhances the pupillary light reflex.

    PubMed

    Binda, Paola; Pereverzeva, Maria; Murray, Scott O

    2013-01-30

    One longstanding question is how early in the visual system attention exerts its influence. Here we show that an effect of attention can be measured at the earliest possible stage of visual information processing, as a change in the optics of the eye. We tested human subjects and found that covertly attending to bright surfaces results in an enhanced pupillary light reflex (PLR)-the pupillary constriction that occurs in response to light increments. The PLR optimizes the optical quality of the retinal image across illumination conditions, increasing sensitivity by modulating retinal illumination, and improving acuity by reducing spherical aberrations. The attentional modulation of the PLR that we describe constitutes a new mechanism through which vision is affected by attention; we discuss three alternatives for the neural substrates of this effect, including the possibility that attention might act indirectly, via its well established effects in early visual cortex. PMID:23365255

  6. Pupillary dynamics reveal computational cost in sentence planning.

    PubMed

    Sevilla, Yamila; Maldonado, Mora; Shalóm, Diego E

    2014-01-01

    This study investigated the computational cost associated with grammatical planning in sentence production. We measured people's pupillary responses as they produced spoken descriptions of depicted events. We manipulated the syntactic structure of the target by training subjects to use different types of sentences following a colour cue. The results showed higher increase in pupil size for the production of passive and object dislocated sentences than for active canonical subject-verb-object sentences, indicating that more cognitive effort is associated with more complex noncanonical thematic order. We also manipulated the time at which the cue that triggered structure-building processes was presented. Differential increase in pupil diameter for more complex sentences was shown to rise earlier as the colour cue was presented earlier, suggesting that the observed pupillary changes are due to differential demands in relatively independent structure-building processes during grammatical planning. Task-evoked pupillary responses provide a reliable measure to study the cognitive processes involved in sentence production. PMID:24712982

  7. Flow modulates myogenic responses in isolated microperfused rabbit afferent arterioles via endothelium-derived nitric oxide.

    PubMed Central

    Juncos, L A; Garvin, J; Carretero, O A; Ito, S

    1995-01-01

    Flow may be a physiological stimulus of the endothelial release of nitric oxide (NO) and prostaglandins (PGs). We tested the hypothesis that pressure-induced constriction of the glomerular afferent arteriole (Af-Art) is modulated by luminal flow via endothelial production of NO. We microdissected the terminal segment of an interlobular artery together with two Af-Arts, their glomeruli (GL) and efferent arterioles (Ef-Art). The two Af-Arts were perfused simultaneously from the interlobular artery, while one Ef-Art was occluded. Since the arteriolar perfusate contained 5% albumin, oncotic pressure built up in the glomerulus with the occluded Ef-Art and opposed the force of filtration, resulting in little or no flow through the corresponding Af-Art. Thus this preparation allowed us to observe free-flow and no-flow Af-Arts simultaneously during stepwise 30-mmHg increases in intraluminal pressure (from 30 to 120 mmHg). Pressure-induced constriction was weaker in free-flow than no-flow Af-Arts, with the luminal diameter decreasing by 11.1 +/- 1.7 and 25.6 +/- 2.3% (n = 30), respectively, at 120 mmHg. To examine whether flow modulates myogenic constriction through endothelium-derived NO and/or PGs, we examined pressure-induced constriction before and after (a) disruption of the endothelium, (b) inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME), or (c) inhibition of cyclooxygenase with indomethacin. Both endothelial disruption and L-NAME augmented pressure-induced constriction in free-flow but not no-flow Af-Arts, abolishing the differences between the two. However, indomethacin had no effect in either free-flow or no-flow Af-Arts. These results suggest that intraluminal flow attenuates pressure-induced constriction in Af-Arts via endothelium-derived NO. Thus flow-stimulated NO release may be important in the fine control of glomerular hemodynamics. Images PMID:7769114

  8. The Pupillary Light Reflex in Idiopathic Intracranial Hypertension

    PubMed Central

    Park, Jason C.; Moss, Heather E.; McAnany, J. Jason

    2016-01-01

    Purpose To evaluate the effects of idiopathic intracranial hypertension (IIH) on rod-, cone-, and melanopsin-mediated pupillary light reflexes (PLRs). Methods Pupillary light reflexes elicited by full-field, brief-flash stimuli were recorded in 13 IIH patients and 13 normal controls. Subjects were dark-adapted for 10 minutes and the PLR was recorded in response to short-wavelength flashes (0.001 cd/m2: rod condition; 450 cd/m2: melanopsin condition). Subjects were then exposed to a rod-suppressing field and 10 cd/m2 long-wavelength flashes were presented (cone condition). Pupillary light reflexes were quantified as the maximum transient constriction (rod and cone conditions) and the post-illumination pupil constriction (melanopsin condition), relative to the baseline pupil size. Diagnostic power was evaluated using receiver operating characteristic (ROC) analysis. Results The IIH patients had significantly smaller PLRs under the melanopsin (P < 0.001) and rod (P = 0.04) paradigms; a trend for reduced cone-mediated PLRs was also found (P = 0.08). Receiver operating characteristic analysis indicated areas under the curves (AUC) of 0.83 (melanopsin-meditated; P = 0.001), 0.71 (rod-mediated; P = 0.07), and 0.77 (cone-mediated; P = 0.02). The AUC (0.90, P < 0.001), sensitivity (85%), and specificity (85%) were high for ROC analysis performed on the mean of the rod, cone, and melanopsin PLRs. Conclusions Pupillary light reflex reductions in IIH patients indicate compromised RGC function. PLR measurement, particularly under rod- and melanopsin-mediated conditions, may be a useful adjunct to standard clinical measures of visual function in IIH. PMID:26746015

  9. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

    PubMed

    Xiao, Bo; Zanoun, Rami R; Carvell, George E; Simons, Daniel J; Washington, Kia M

    2016-03-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. PMID:26792886

  10. Laser-evoked cortical responses in freely-moving rats reflect the activation of C-fibre afferent pathways.

    PubMed

    Xia, X L; Peng, W W; Iannetti, G D; Hu, L

    2016-03-01

    The limited success of translating basic animal findings into effective clinical treatments of pain can be partly ascribed to the use of sub-optimal models. Murine models of pain often consist in recording (1) threshold responses (like the tail-flick reflex) elicited by (2) non-nociceptive specific inputs in (3) anaesthetized animals. The direct cortical recording of laser-evoked potentials (LEPs) elicited by stimuli of graded energies in freely-moving rodents avoids these three important pitfalls, and has thus the potential of improving such translation. Murine LEPs are classically reported to consist of two distinct components, reflecting the activity of Aδ- and C-fibre afferent pathways. However, we have recently demonstrated that the so-called "Aδ-LEPs" in fact reflect the activation of the auditory system by laser-generated ultrasounds. Here we used ongoing white noise to avoid the confound represented by the early auditory response, and thereby comprehensively characterized the physiological properties of C-fibre LEPs recorded directly from the exposed surface of the rat brain. Stimulus-response functions indicated that response amplitude is positively related to the stimulus energy, as well as to nocifensive behavioral score. When displayed using average reference, murine LEPs consist of three distinct deflections, whose polarity, order, and topography are surprisingly similar to human LEPs. The scalp topography of the early N1 wave is somatotopically-organized, likely reflecting the activity of the primary somatosensory cortex, while topographies of the later N2 and P2 waves are more centrally distributed. These results indicate that recording LEPs in freely-moving rats is a valid model to improve the translation of animal results to human physiology and pathophysiology. PMID:26747747

  11. Laser-evoked cortical responses in freely-moving rats reflect the activation of C-fibre afferent pathways

    PubMed Central

    Xia, X.L.; Peng, W.W.; Iannetti, G.D.; Hu, L.

    2016-01-01

    The limited success of translating basic animal findings into effective clinical treatments of pain can be partly ascribed to the use of sub-optimal models. Murine models of pain often consist in recording (1) threshold responses (like the tail-flick reflex) elicited by (2) non-nociceptive specific inputs in (3) anaesthetized animals. The direct cortical recording of laser-evoked potentials (LEPs) elicited by stimuli of graded energies in freely-moving rodents avoids these three important pitfalls, and has thus the potential of improving such translation. Murine LEPs are classically reported to consist of two distinct components, reflecting the activity of Aδ- and C-fibre afferent pathways. However, we have recently demonstrated that the so-called “Aδ-LEPs” in fact reflect the activation of the auditory system by laser-generated ultrasounds. Here we used ongoing white noise to avoid the confound represented by the early auditory response, and thereby comprehensively characterized the physiological properties of C-fibre LEPs recorded directly from the exposed surface of the rat brain. Stimulus–response functions indicated that response amplitude is positively related to the stimulus energy, as well as to nocifensive behavioral score. When displayed using average reference, murine LEPs consist of three distinct deflections, whose polarity, order, and topography are surprisingly similar to human LEPs. The scalp topography of the early N1 wave is somatotopically-organized, likely reflecting the activity of the primary somatosensory cortex, while topographies of the later N2 and P2 waves are more centrally distributed. These results indicate that recording LEPs in freely-moving rats is a valid model to improve the translation of animal results to human physiology and pathophysiology. PMID:26747747

  12. Deletion of the murine ATP/UTP receptor P2Y2 alters mechanical and thermal response properties in polymodal cutaneous afferents.

    PubMed

    Molliver, Derek C; Rau, Kristofer K; Jankowski, Michael P; Soneji, Deepak J; Baumbauer, Kyle M; Koerber, H Richard

    2016-09-22

    P2Y2 is a member of the P2Y family of G protein-coupled nucleotide receptors that is widely co-expressed with TRPV1 in peripheral sensory neurons of the dorsal root ganglia. To characterize P2Y2 function in cutaneous afferents, intracellular recordings from mouse sensory neurons were made using an ex vivo preparation in which hindlimb skin, saphenous nerve, dorsal root ganglia and spinal cord are dissected intact. The peripheral response properties of individual cutaneous C-fibers were analyzed using digitally controlled mechanical and thermal stimuli in male P2Y2(+/+) and P2Y2(-/-) mice. Selected sensory neurons were labeled with Neurobiotin and further characterized by immunohistochemistry. In wildtype preparations, C-fibers responding to both mechanical and thermal stimuli (CMH or CMHC) preferentially bound the lectin marker IB4 and were always immunonegative for TRPV1. Conversely, cells that fired robustly to noxious heat, but were insensitive to mechanical stimuli, were TRPV1-positive and IB4-negative. P2Y2 gene deletion resulted in reduced firing by TRPV1-negative CMH fibers to a range of heat stimuli. However, we also identified an atypical population of IB4-negative, TRPV1-positive CMH fibers. Compared to wildtype CMH fibers, these TRPV1-positive neurons exhibited lower firing rates in response to mechanical stimulation, but had increased firing to noxious heat (43-51°C). Collectively, these results demonstrate that P2Y2 contributes to response properties of cutaneous afferents, as P2Y2 deletion reduces responsiveness of conventional unmyelinated polymodal afferents to heat and appears to result in the acquisition of mechanical responsiveness in a subset of TRPV1-expressing afferents. PMID:27393251

  13. Pupillary block after intraocular lens implantation.

    PubMed

    Van Buskirk, E M

    1983-01-01

    Seventeen patients, ranging in age from 40 to 86 years, developed pupillary block detected one week to three years after intraocular lens implantation. Sixteen of the implants were anterior chamber intraocular lenses and one was a posterior chamber intraocular lens. Despite iris bombé that closed the anterior chamber angle, many cases were asymptomatic and were discovered fortuitously during routine postoperative examinations. Laser iridotomy or iridectomy eliminated the pupillary block in all 17 cases, but permanent synechial closure of a portion of the anterior chamber angle persisted in most cases and sometimes required medication or further surgery. One eye eventually lost all light perception. PMID:6849369

  14. Similar nociceptive afferents mediate psychophysical and electrophysiological responses to heat stimulation of glabrous and hairy skin in humans

    PubMed Central

    Iannetti, G D; Zambreanu, L; Tracey, I

    2006-01-01

    The ability to perceive and withdraw rapidly from noxious environmental stimuli is crucial for survival. When heat stimuli are applied to primate hairy skin, first pain sensation is mediated by type-II A-fibre nociceptors (II-AMHs). In contrast, the reported absence of first pain and II-AMH microneurographical responses when heat stimuli are applied to the hand palm has led to the notion that II-AMHs are lacking in this primate glabrous skin. The aim of this study was to assess the effect of hairy and glabrous skin stimulation on neural transmission of nociceptive inputs elicited by different kinds of thermal heating. We recorded psychophysical and EEG brain responses to radiant (laser-evoked potentials, LEPs) and contact heat stimuli (contact heat-evoked potentials, CHEPs) delivered to the dorsum and the palm of the hand in normal volunteers. Brain responses were analysed at a single-trial level, using an automated approach based on multiple linear regression. Laser stimulation of hairy and glabrous skin at the same energy elicited remarkably similar psychophysical ratings and LEPs. This finding provides strong evidence that first pain to heat does exist in glabrous skin, and suggests that similar nociceptive afferents, with the physiological properties of II-AMHs, mediate first pain to heat stimulation of glabrous and hairy skin in humans. In contrast, when contact heat stimuli were employed, a significantly higher nominal temperature had to be applied to glabrous skin in order to achieve psychophysical ratings similar to those obtained following hairy skin stimulation, and CHEPs following glabrous skin stimulation had significantly longer latencies (N2 wave, +25%; P2 wave, +24%) and smaller amplitudes (N2 wave, −40%; P2 wave, −44%) than CHEPs following hairy skin stimulation. Irrespective of the stimulated territory, CHEPs always had significantly longer latencies (hairy skin N2 wave, +75%; P2 wave, +56%) and smaller amplitudes (hairy skin N2 wave, −42%; P

  15. Pupillary block glaucoma following intraocular lens implantation.

    PubMed

    Kielar, R A; Stambaugh, J L

    1982-08-01

    Seven cases of pupillary block granuloma occurred in a series of 665 consecutive cases of cataract extraction with insertion of an iris supported intraocular lens, an overall incidence of 1%. The incidence with an iris plane lens was 1.7%, and for all other styles used the incidence was 0.3%. Common factors noted were iris plane intraocular lens and early postoperative complications predisposing to pupillary block. In four of the seven cases, there was a period of normal intraocular pressure followed by elevated intraocular tension with a deep central anterior chamber two weeks to fifteen months following cataract extraction, with subsequent development of corneal edema and typical shallowing of the anterior chamber with iris bombe. Five of seven cases ultimately regained control of intraocular pressure although extensive peripheral anterior synechia were present. No patient ultimately had a visual acuity better than 20/50. PMID:7133608

  16. Validating a Population Model of Tactile Mechanotransduction of Slowly Adapting Type I Afferents at Levels of Skin Mechanics, Single-unit Response and Psychophysics

    PubMed Central

    Gerling, Gregory J.; Rivest, Isabelle I.; Lesniak, Daine R.; Scanlon, Jacob R.; Wan, Lingtian

    2015-01-01

    Previous models of touch have linked skin mechanics to neural firing rate, neural dynamics to action potential elicitation, and mechanoreceptor populations to psychophysical discrimination. However, no one model spans all levels. The objective of work herein is to build a multi-level, computational model of tactile neurons embedded in cutaneous skin, and then validate its predictions of skin surface deflection, single-afferent firing to indenter shift, and population response for sphere discrimination. The model includes a 3D finite element representation of the distal phalange with hyper- and visco-elastic mechanics. Distributed over its surface, a population of receptor models is comprised of bi-phasic functions to represent Merkel cells’ transformation of stress/strain to membrane current and a leaky integrate-and-fire neuronal models to generate the timing of action potentials. After including neuronal noise, the predictions of two population encoding strategies (Gradient Sum and Euclidean Distance) are compared to psychophysical discrimination of spheres. Results indicate that predicted skin surface deflection matches Srinivasan's observations for 50 micron and 3.17 mm diameter cylinders and single-afferent responses achieve R2=0.81 when compared to Johnson’s recordings. Discrimination results correlate with Goodwin’s experiments, whereby 287 and 365 m−1 spheres are more discriminable than 287 and 296 m−1. PMID:24960553

  17. Validating a population model of tactile mechanotransduction of slowly adapting type I afferents at levels of skin mechanics, single-unit response and psychophysics.

    PubMed

    Gerling, Gregory J; Rivest, Isabelle I; Lesniak, Daine R; Scanlon, Jacob R; Wan, Lingtian

    2014-01-01

    Previous models of touch have linked skin mechanics to neural firing rate, neural dynamics to action potential elicitation, and mechanoreceptor populations to psychophysical discrimination. However, no one model spans all levels. The objective of work herein is to build a multi-level, computational model of tactile neurons embedded in cutaneous skin, and then validate its predictions of skin surface deflection, single-afferent firing to indenter shift, and population response for sphere discrimination. The model includes a 3D finite element representation of the distal phalange with hyper- and visco-elastic mechanics. Distributed over its surface, a population of receptor models is comprised of bi-phasic functions to represent Merkel cells' transformation of stress/strain to membrane current and a leaky integrate-and-fire neuronal models to generate the timing of action potentials. After including neuronal noise, the predictions of two population encoding strategies (gradient sum and euclidean distance) are compared to psychophysical discrimination of spheres. Results indicate that predicted skin surface deflection matches Srinivasan's observations for 50 micron and 3.17 mm diameter cylinders and single-afferent responses achieve R(2) = 0.81 when compared to Johnson's recordings. Discrimination results correlate with Goodwin's experiments, whereby 287 and 365 m(-1) spheres are more discriminable than 287 and 296 m(-1). PMID:24960553

  18. Pupillary escape quantification with an image-processing system in clinical perimetry

    NASA Astrophysics Data System (ADS)

    Suaste-Gomez, Ernesto; Rivera-Arzola, Palmira; Salazar-Rodarte, Victor

    1996-05-01

    We present a new technique to quantify the pupillary escape with an image-processing system during visual field examination in routine ophthalmological practice. Visual field evaluation is important in the detection, diagnosis and assessment of ophthalmologic and neurologic dysfunction. With the conditions during the perimetric study: an initially large pupil and a small step light stimuli, it presents the pupillary escape where the pupil responds with a very fast constriction and then redilates almost back to its original level. In order to measure this response, we obtain automatic and objective determinations for each spot of light in peripheric and central zones. The automatic perimeter is based on the physical dimensions of Goldmann perimeter and the index projector is based on fiber optics target. The pupillary escape and the pupillary response are captured by means of an infrared-sensitive camera and recorded in a VCR to analyze off line with an image processing system. This system consists of a computer equipped with a frame grabber DT2853 and eye movements detector for monitoring the initial position of the eye, during the examination. The algorithms to detect and analyze are: mensuration (area, perimeter, latencies) and matching template based on the stochastic sign change criterion.

  19. Cortisol, Chromogranin A, and Pupillary Responses Evoked by Speech Recognition Tasks in Normally Hearing and Hard-of-Hearing Listeners: A Pilot Study.

    PubMed

    Kramer, Sophia E; Teunissen, Charlotte E; Zekveld, Adriana A

    2016-01-01

    Pupillometry is one method that has been used to measure processing load expended during speech understanding. Notably, speech perception (in noise) tasks can evoke a pupil response. It is not known if there is concurrent activation of the sympathetic nervous system as indexed by salivary cortisol and chromogranin A (CgA) and whether such activation differs between normally hearing (NH) and hard-of-hearing (HH) adults. Ten NH and 10 adults with mild-to-moderate hearing loss (mean age 52 years) participated. Two speech perception tests were administered in random order: one in quiet targeting 100% correct performance and one in noise targeting 50% correct performance. Pupil responses and salivary samples for cortisol and CgA analyses were collected four times: before testing, after the two speech perception tests, and at the end of the session. Participants rated their perceived accuracy, effort, and motivation. Effects were examined using repeated-measures analyses of variance. Correlations between outcomes were calculated. HH listeners had smaller peak pupil dilations (PPDs) than NH listeners in the speech in noise condition only. No group or condition effects were observed for the cortisol data, but HH listeners tended to have higher cortisol levels across conditions. CgA levels were larger at the pretesting time than at the three other test times. Hearing impairment did not affect CgA. Self-rated motivation correlated most often with cortisol or PPD values. The three physiological indicators of cognitive load and stress (PPD, cortisol, and CgA) are not equally affected by speech testing or hearing impairment. Each of them seem to capture a different dimension of sympathetic nervous system activity. PMID:27355762

  20. Age-dependent pupillary light reflex parameters in children.

    PubMed

    Daluwatte, Chathuri; Miles, Judith H; Christ, Shawn E; Beversdorf, David Q; Lofgreen, Andrew; Berliner, Nathan; Yao, Gang

    2012-01-01

    Pupillary light reflex (PLR) refers to the phenomenon where pupil size changes in response to stimulation with a flash of light. It is a simple functional test that can reveal dysfunctions associated with the PLR pathway. Although abnormal PLR responses have been reported in many neurological disorders, few studies investigated neurodevelopmental effects on PLR parameters. We studied the effect of age on PLR in a group of 6 to 17 year old children with typical development. A significant and consistent age effect was found on PLR latency in children younger than 10 years old. Age effects were also observed in resting pupil diameter and constriction amplitude. However such age related trends were not observed in children with neurodevelopment disorders. These results suggest that PLR has the potential to be used as a simple noninvasive tool for monitoring neurodevelopment in children. PMID:23366750

  1. Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat.

    PubMed

    Casals-Díaz, Laura; Vivó, Meritxell; Navarro, Xavier

    2009-05-01

    Peripheral nerve injuries induce plastic changes on primary afferent fibers and on the spinal circuitry, which are related to the emergence of neuropathic pain. In this study we compared three models of sciatic nerve injury in the rat with different degrees of damage and impact on regeneration capability: crush nerve injury, chronic constriction injury (CCI) and spared nerve injury (SNI). All three models were characterized by means of nerve histology, in order to describe the degenerative and regenerative process of injured axons. Nociceptive responses were evaluated by mechanical and thermal algesimetry tests. Crush animals displayed higher withdrawal thresholds on the ipsilateral paw compared to the contralateral during the time of denervation, while CCI and SNI animals showed mechanical and thermal hyperalgesia. Central plasticity was evaluated by immunohistochemical labeling of non-peptidergic (IB4-positive) and peptidergic (substance P-positive) nociceptive C-fibers on L4-L6 spinal cord sections. After crush nerve injury and SNI, we observed progressive and sustained reduction of IB4 and SP immunolabeling at the sciatic projection territory in the superficial laminae of the dorsal horn, which affected only the tibial and peroneal nerves projection areas in the case of SNI. After CCI, changes on SP-immunoreactivity were not observed, and IB4-immunoreactive area decreased initially but recovered to normal levels on the second week post-injury. Thus, nociceptive responses depend on the type of injury, and the immunoreactivity pattern of afferent fibers at the spinal cord display changes less pronounced after partial than complete sciatic nerve injury. Although signs of neuropathic pain appear in all three lesion models, nociceptive responses and central plasticity patterns differ between them. PMID:19416675

  2. Pupillary light reflex to light inside the natural blind spot.

    PubMed

    Miyamoto, Kentaro; Murakami, Ikuya

    2015-01-01

    When a light stimulus covers the human natural blind spot (BS), perceptual filling-in corrects for the missing information inside the BS. Here, we examined whether a filled-in surface of light perceived inside the BS affects the size of the short-latency pupillary light reflex (PLR), a pupil response mediated by a subcortical pathway for unconscious vision. The PLR was not induced by a red surface that was physically absent but perceptually filled-in inside the BS in the presence of a red ring surrounding it. However, a white large disk covering the BS unexpectedly induced a larger PLR than a white ring surrounding the BS border did, even though these two stimuli must be equivalent for the visual system, and trial-by-trial percepts did not predict PLR size. These results suggest that some physiological mechanism, presumably the retinal cells containing the photopigment melanopsin, receives the light projected inside the BS and enhances PLR. PMID:26115182

  3. Nonlinear analysis of pupillary dynamics.

    PubMed

    Onorati, Francesco; Mainardi, Luca Tommaso; Sirca, Fabiola; Russo, Vincenzo; Barbieri, Riccardo

    2016-02-01

    Pupil size reflects autonomic response to different environmental and behavioral stimuli, and its dynamics have been linked to other autonomic correlates such as cardiac and respiratory rhythms. The aim of this study is to assess the nonlinear characteristics of pupil size of 25 normal subjects who participated in a psychophysiological experimental protocol with four experimental conditions, namely “baseline”, “anger”, “joy”, and “sadness”. Nonlinear measures, such as sample entropy, correlation dimension, and largest Lyapunov exponent, were computed on reconstructed signals of spontaneous fluctuations of pupil dilation. Nonparametric statistical tests were performed on surrogate data to verify that the nonlinear measures are an intrinsic characteristic of the signals. We then developed and applied a piecewise linear regression model to detrended fluctuation analysis (DFA). Two joinpoints and three scaling intervals were identified: slope α0, at slow time scales, represents a persistent nonstationary long-range correlation, whereas α1 and α2, at middle and fast time scales, respectively, represent long-range power-law correlations, similarly to DFA applied to heart rate variability signals. Of the computed complexity measures, α0 showed statistically significant differences among experimental conditions (p<0.001). Our results suggest that (a) pupil size at constant light condition is characterized by nonlinear dynamics, (b) three well-defined and distinct long-memory processes exist at different time scales, and (c) autonomic stimulation is partially reflected in nonlinear dynamics. PMID:26351899

  4. Unilateral pupillary dilatation following septoplasty: cause for concern?

    PubMed

    Shakeel, Muhammad; Trinidade, Aaron; Khan, Imran; Johnston, Graham; Hussain, Akhtar

    2013-07-01

    We report and explain unilateral pupillary dilatation following routine septoplasty and trimming of inferior turbinates. The unilateral pupillary dilatation was caused by inadvertent instillation of sympathomimetic, (xylometazoline hydrochloride) in the eye during preparation for nasal surgery. The effect was short-lived and the patient made a full recovery. Unilateral pupillary dilatation after sinonasal surgery can be alarming due to the possibility of injury to the globe and intracranial haemorrhage but can also be explained by the mydriatic effect of the sympathomimetic nasal drops and sprays used to decongest the nose. Such possibility should be borne in mind and would help to explain and reduce the anxiety and avoid unnecessary investigations. PMID:23823962

  5. High frequency ultrasound imaging in pupillary block glaucoma.

    PubMed Central

    Aslanides, I M; Libre, P E; Silverman, R H; Reinstein, D Z; Lazzaro, D R; Rondeau, M J; Harmon, G K; Coleman, D J

    1995-01-01

    BACKGROUND--The diagnosis of pupillary block glaucoma requires sufficient clarity of the ocular media. This is particularly important for assessment of both the presence and patency of an iridotomy, and the determination of central anterior chamber depth. METHODS--High frequency ultrasonography was used in three patients with suspected pupillary block to determine iris configuration, posterior chamber volume, and ciliary body conformation. RESULTS--All patients demonstrated high frequency ultrasonographic findings consistent with pupillary block: iris bombé, a formed posterior chamber, and a lack of anterior rotation of the ciliary processes. CONCLUSION--High frequency ultrasound imaging appears to be a valuable adjunct in making or corroborating the diagnosis of pupillary block glaucoma. Images PMID:8534666

  6. Whisker-related afferents in superior colliculus.

    PubMed

    Castro-Alamancos, Manuel A; Favero, Morgana

    2016-05-01

    Rodents use their whiskers to explore the environment, and the superior colliculus is part of the neural circuits that process this sensorimotor information. Cells in the intermediate layers of the superior colliculus integrate trigeminotectal afferents from trigeminal complex and corticotectal afferents from barrel cortex. Using histological methods in mice, we found that trigeminotectal and corticotectal synapses overlap somewhat as they innervate the lower and upper portions of the intermediate granular layer, respectively. Using electrophysiological recordings and optogenetics in anesthetized mice in vivo, we showed that, similar to rats, whisker deflections produce two successive responses that are driven by trigeminotectal and corticotectal afferents. We then employed in vivo and slice experiments to characterize the response properties of these afferents. In vivo, corticotectal responses triggered by electrical stimulation of the barrel cortex evoke activity in the superior colliculus that increases with stimulus intensity and depresses with increasing frequency. In slices from adult mice, optogenetic activation of channelrhodopsin-expressing trigeminotectal and corticotectal fibers revealed that cells in the intermediate layers receive more efficacious trigeminotectal, than corticotectal, synaptic inputs. Moreover, the efficacy of trigeminotectal inputs depresses more strongly with increasing frequency than that of corticotectal inputs. The intermediate layers of superior colliculus appear to be tuned to process strong but infrequent trigeminal inputs and weak but more persistent cortical inputs, which explains features of sensory responsiveness, such as the robust rapid sensory adaptation of whisker responses in the superior colliculus. PMID:26864754

  7. Pupillary behavior in relation to wavelength and age.

    PubMed

    Lobato-Rincón, Luis-Lucio; Cabanillas-Campos, Maria Del Carmen; Bonnin-Arias, Cristina; Chamorro-Gutiérrez, Eva; Murciano-Cespedosa, Antonio; Sánchez-Ramos Roda, Celia

    2014-01-01

    Pupil light reflex can be used as a non-invasive ocular predictor of cephalic autonomic nervous system integrity. Spectral sensitivity of the pupil's response to light has, for some time, been an interesting issue. It has generally, however, only been investigated with the use of white light and studies with monochromatic wavelengths are scarce. This study investigates the effects of wavelength and age within three parameters of the pupil light reflex (amplitude of response, latency, and velocity of constriction) in a large sample of younger and older adults (N = 97), in mesopic conditions. Subjects were exposed to a single light stimulus at four different wavelengths: white (5600°K), blue (450 nm), green (510 nm), and red (600 nm). Data was analyzed appropriately, and, when applicable, using the General Linear Model (GLM), Randomized Complete Block Design (RCBD), Student's t-test and/or ANCOVA. Across all subjects, pupillary response to light had the greatest amplitude and shortest latency in white and green light conditions. In regards to age, older subjects (46-78 years) showed an increased latency in white light and decreased velocity of constriction in green light compared to younger subjects (18-45 years old). This study provides data patterns on parameters of wavelength-dependent pupil reflexes to light in adults and it contributes to the large body of pupillometric research. It is hoped that this study will add to the overall evaluation of cephalic autonomic nervous system integrity. PMID:24795595

  8. Pupillary behavior in relation to wavelength and age

    PubMed Central

    Lobato-Rincón, Luis-Lucio; Cabanillas-Campos, Maria del Carmen; Bonnin-Arias, Cristina; Chamorro-Gutiérrez, Eva; Murciano-Cespedosa, Antonio; Sánchez-Ramos Roda, Celia

    2014-01-01

    Pupil light reflex can be used as a non-invasive ocular predictor of cephalic autonomic nervous system integrity. Spectral sensitivity of the pupil's response to light has, for some time, been an interesting issue. It has generally, however, only been investigated with the use of white light and studies with monochromatic wavelengths are scarce. This study investigates the effects of wavelength and age within three parameters of the pupil light reflex (amplitude of response, latency, and velocity of constriction) in a large sample of younger and older adults (N = 97), in mesopic conditions. Subjects were exposed to a single light stimulus at four different wavelengths: white (5600°K), blue (450 nm), green (510 nm), and red (600 nm). Data was analyzed appropriately, and, when applicable, using the General Linear Model (GLM), Randomized Complete Block Design (RCBD), Student's t-test and/or ANCOVA. Across all subjects, pupillary response to light had the greatest amplitude and shortest latency in white and green light conditions. In regards to age, older subjects (46–78 years) showed an increased latency in white light and decreased velocity of constriction in green light compared to younger subjects (18–45 years old). This study provides data patterns on parameters of wavelength-dependent pupil reflexes to light in adults and it contributes to the large body of pupillometric research. It is hoped that this study will add to the overall evaluation of cephalic autonomic nervous system integrity. PMID:24795595

  9. Involvement of a CCK-dependent capsaicin-sensitive afferent pathway in the inhibitory effect of pinaverium bromide on the colonic motor response to eating in rats.

    PubMed

    Fioramonti, J; Christen, M O; Dupre, I; Bueno, L

    1997-01-01

    The effects of pinaverium bromide on the stimulation of colonic motility induced by meal and cholecystokinin (CCK) were investigated in rats chronically fitted with intraparietal electrodes on the proximal colon and previously treated or not by capsaicin. Pinaverium bromide inhibited in a dose-related manner (2-50 mg/kg, per os) the increase in colonic spike burst frequency induced by a 3 g meal or CCK-8 (2 micrograms/kg, i.v.). The CCK-A and CCK-B antagonists, devazepide and L 365260 (100 micrograms/kg, i.p.), respectively, inhibited the postprandial colonic motor response while only L 365260 reduced the CCK-induced stimulation. The effects of pinaverium bromide and CCK antagonists were not observed in capsaicin-treated animals. Moreover, CCK-8 (2 micrograms/kg, i.v.) did not stimulate colonic motility after capsaicin treatment. The inhibition of postprandial colonic motility by pinaverium bromide, given orally at therapeutic doses, involves a CCK-dependent pathway which requires the integrity of capsaicin-sensitive afferents. PMID:9243254

  10. Contractile properties of afferent and efferent arterioles.

    PubMed

    Ito, S; Abe, K

    1997-07-01

    1. The balance of vascular tone of the afferent and efferent arteriole is a crucial determinant of glomerular haemodynamics. Despite their intimate anatomical relationship in the juxtaglomerular apparatus, the mechanisms that regulate afferent and efferent arteriolar tone are different. 2. In the afferent arteriole, two intrinsic mechanisms, the myogenic response and macula densa-mediated tubuloglomerular feedback (TGF) play a dominant role, maintaining the glomerular filtration rate (GFR) at a constant level over a wide range of renal perfusion pressure. Studies have shown that these two mechanisms are modulated by nitric oxide (NO). In addition, an interaction between TGF and angiotensin II (AngII) seems to be essential to maintaining GFR despite large variations in daily intake of salt and water. 3. In the efferent arteriole, neither myogenic response nor TGF seems to be important, while AngII is one major factor involved in the control of vascular resistance. In addition, recent studies have provided evidence that NO and prostaglandins produced by the glomerulus may control resistance of the downstream efferent arteriole. 4. As the early segment of the efferent arteriole resides within the glomerulus, various autacoid hormones produced by the glomerulus may reach and directly act on this segment, thereby controlling the glomerular capillary pressure. Thus, it would be important to understand the differences in the mechanisms operating at the afferent and efferent arteriole, as well as their alterations in various physiological and pathological conditions. PMID:9248673

  11. PERSISTENT PUPILLARY MEMBRANE OR ACCESSORY IRIS MEMBRANE?.

    PubMed

    Gavriş, Monica; Horge, Ioan; Avram, Elena; Belicioiu, Roxana; Olteanu, Ioana Alexandra; Kedves, Hanga

    2015-01-01

    Frequently, in literature and curent practice, accessory iris membrane (AIM) and persistant pupillary membrane (PPM) are confused. Both AIM and PPM are congenital iris anomalies in which fine or thick iris strands arrise form the collarette and obscure the pupil. AIM, which is also called iris duplication, closely resembles the normal iris tissue in color and thickness and presents a virtual second pseudopupil aperture in the centre while PPM even in its extreme forms presents as a translucent or opaque membranous structure that extends across the pupil and has no pseudopupil. Mydriatiscs, laser treatment or surgery is used to clear the visual axis and optimize visual development. Surgical intervention is reserved for large, dense AIMs and PPMs. Our patient, a 29 year old male, has come with bilateral dense AIM, bilateral compound hyperopic astigmatism, BCVA OD = 0.6, BCVA OS = 0.4, IOP OU = 17 mmHg. To improve the visual acuity of the patient we decided to do a bilateral membranectomy, restoring in this way transparency of the visual axis. After surgery, the visual acuity improved to BCVA OD= 0.8, BCVA OS=0.8. PMID:26978889

  12. Unmyelinated type II afferent neurons report cochlear damage

    PubMed Central

    Liu, Chang; Glowatzki, Elisabeth; Fuchs, Paul Albert

    2015-01-01

    In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term “noxacusis” to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage. Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear. PMID:26553995

  13. Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

    PubMed Central

    Bird, Alex D.; Richardson, Magnus J. E.

    2014-01-01

    Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modified during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony set by the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture. PMID:24523691

  14. Pupillary Contagion in Infancy: Evidence for Spontaneous Transfer of Arousal.

    PubMed

    Fawcett, Christine; Wesevich, Victoria; Gredebäck, Gustaf

    2016-07-01

    Pupillary contagion-responding to pupil size observed in other people with changes in one's own pupil-has been found in adults and suggests that arousal and other internal states could be transferred across individuals using a subtle physiological cue. Examining this phenomenon developmentally gives insight into its origins and underlying mechanisms, such as whether it is an automatic adaptation already present in infancy. In the current study, 6- and 9-month-olds viewed schematic depictions of eyes with smaller and larger pupils-pairs of concentric circles with smaller and larger black centers-while their own pupil sizes were recorded. Control stimuli were comparable squares. For both age groups, infants' pupil size was greater when they viewed large-center circles than when they viewed small-center circles, and no differences were found for large-center compared with small-center squares. The findings suggest that infants are sensitive and responsive to subtle cues to other people's internal states, a mechanism that would be beneficial for early social development. PMID:27207876

  15. Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin.

    PubMed

    Hogan, Dale; Baker, Alyssa L; Morón, Jose A; Carlton, Susan M

    2013-11-01

    Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity-hyperalgesia and/or allodynia. We hypothesized that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and tested this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected intraperitoneally with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 hours for 48 hours and killed approximately 12 hours after the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2-minute period and during 5-minute periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in saline-treated mice. Resting background activity was elevated in C-fibers from morphine-treated mice. Both C- and Aδ-fibers had afterdischarge in response to mechanical, heat, and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain and could contribute to opioid-induced hyperalgesia. PMID:23711478

  16. A patient with bilateral persistent pupillary membrane: a conservative approach.

    PubMed

    Kurt, Emin

    2009-01-01

    The author describes the case of a girl with bilateral persistent pupillary membranes and good visual acuity. An otherwise healthy 10-year-old girl presented with persistent pupillary membranes in both eyes since childhood. The patient had ametropic amblyopia, which was treated with spectacles and part-time occlusion therapy, with the patient responding conventionally. After therapy, her best-corrected visual acuity was 20/25 in both eyes. She had stereopsis of 50 seconds of arc, orthophoria, and normal extraocular movements. The remainder of the examination was normal. Patients with bilateral persistent pupillary membranes may not require surgery if there is adequate opening. The author suggests a trial of refractive correction and occlusion therapy before deciding on surgical and laser intervention, even if it seems an absolute requirement. PMID:19791728

  17. Uveitis and pupillary block glaucoma in an aphakic dog.

    PubMed

    Strubbe, Todd

    2002-03-01

    Unilateral uveitis with pupillary occlusion and secondary glaucoma was treated with neodymium:YAG laser iridotomy and iridencleisis in an aphakic 2-year-old male Miniature Schnuauzer. The dog presented 4 months after bilateral phacoemulsification with a complaint of blepharospasm of the left eye. Examination revealed anterior uveitis with pupillary occlusion and iris bombé. A slit-lamp mounted Q-switched Nd:YAG laser was used to create a central iridotomy to deepen the anterior chamber and an iridencleisis was performed to recreate a pupil. The eye remained visual and normotensive over a 6-month follow-up period. PMID:11940241

  18. Identification and properties of parietal pleural afferents in rabbits

    PubMed Central

    Jammes, Yves; Trousse, Delphine; Delpierre, Stéphane

    2005-01-01

    Although pain and dyspnoea are common symptoms in pleural diseases, there are few studies on the sensory innervation of the pleura. Using rabbits, after removal of all muscles in the intercostal space to be studied, we investigated the afferents of the internal intercostal nerve by applying to the internal thoracic wall pieces of gauze soaked in warmed (37°C), buffered saline (mechanical stimulation) or solutions containing lactic acid, inflammatory mediators or capsaicin (chemical stimulation). The afferent conduction velocity ranged from 0.5 to 14 m s−1. Most units (97%) were activated by mechanical stimulation of the pleura (local positive pressure range = 4.5–8.5 cmH2O) and we found a linear relationship between the discharge rate of afferents and the force applied to the thoracic wall. The majority of mechanosensitive units (70%) also responded to one or several chemical agents. Thus, the afferents were activated by lactic acid (49%) and/or a mixture of inflammatory mediators (50%). Local application of capsaicin elicited an initial increased or decreased background afferent activity in 57% of the afferents, a delayed decrease in firing rate being noted in some units initially activated by capsaicin. Capsaicin blocked the afferent response to a further application of inflammatory mediators but did not affect the mechanosensitive units. Thus, sensory endings connected with thin myelinated and unmyelinated fibres in the internal intercostal nerve detect the mechanical and chemical events of pleural diseases. PMID:15975985

  19. Pupillary Motility: Bringing Neuroscience to the Psychiatry Clinic of the Future

    PubMed Central

    Graur, Simona

    2013-01-01

    Modern pupillometry has expanded the study and utility of pupil responses in many new domains including psychiatry, particularly for understanding aspects of cognitive and emotional information processing. Here, we review the applications of pupillometry in psychiatry for understanding patients’ information processing styles, predicting treatment, and augmenting function. In the past year pupillometry has been shown to be useful in specifying cognitive/affective occurrences during experimental tasks and informing clinical diagnoses. Such studies demonstrate the potential of pupillary motility to be used in clinical psychiatry much as it has been in neurology for the past century. PMID:23780801

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

    PubMed

    Mazzone, Stuart B; Undem, Bradley J

    2016-07-01

    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

  1. [Pupillary diameter and pupillary reactions in heroin dependent patients and in patients participating in a methadone and morphine replacement program].

    PubMed

    Linzmayer, L; Fischer, G; Grünberger, J

    1997-01-01

    The computer-assisted static and dynamic light evoked pupillometry (TV-pupillometer 1050, Whittaker Corp.) had been proved to be a sensitive procedure for assessment of the effect of psychoactive drugs. Therefore, this method was used in 26 heroin dependent patients (mean age 24.42 years), 20 methadone substituted patients (mean age 29.75), and 20 morphine-substituted patients (mean age 30.65 years) to answer the question whether there were no differences within the patient groups but significant differences between the patients and healthy normals. Indeed, pupillary diameter (vegetative activation) as well as relative change (pupillary reagibility) showed no significant differences between the heroin dependents, the methadone substitution group and the morphine substitution group. However concerning pupillary diameter and relative change the patient groups differed significantly from the healthy controls. Onset latency revealed no differences within the patient groups and between patient groups and healthy controls respectively. Thus the variable pupillary diameter and relative change could be used to assess the additional application of opiates in patients participating in a substitution program. PMID:9173676

  2. Semicircular Canal Geometry, Afferent Sensitivity And Animal Behavior

    PubMed Central

    Hullar, Timothy A.

    2008-01-01

    The geometry of the semicircular canals has been used in evolutionary studies to predict the behaviors of extinct animals. These predictions have relied on an assumption that the responses of the canals can be determined from their dimensions, and that an organism’s behavior can be determined from these responses. However, the relationship between a canal’s sensitivity and its size is not well known. An intraspecies comparison among canal responses in each of three species (cat, squirrel monkey, and pigeon) was undertaken to evaluate various models of canal function and determine how their dimensions may be related to afferent physiology. All models predicted the responses of the cat afferents, but the models performed less well for squirrel monkey and pigeon. Possible causes for this discrepancy include incorrectly assuming that afferent responses accurately represent canal function, or errors in current biophysical models of the canals. These findings leave open the question as to how reliably canal anatomy can be used to estimate afferent responses and how closely afferent responses are related to behavior. Other labyrinthine features—such as orientation of the horizontal canal, which is reliably held near earth-horizontal across many species—may be better to use when extrapolating the posture and related behavior of extinct animals from labyrinthine morphology. PMID:16550591

  3. Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

    PubMed Central

    Brumovsky, Pablo R.; Gebhart, Gerald F.

    2010-01-01

    Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding characteristics of colorectal afferents. The colorectum with PN attached was dissected, opened longitudinally, and pinned flat in a Sylgard-lined chamber. Action potentials of afferent fibers evoked by circumferential stretch (servo-controlled force actuator) were recorded from the PN. Stretch-sensitive fibers were categorized into the following four groups: colonic muscular, colonic muscular/mucosal, rectal muscular, and rectal muscular/mucosal. Seventy-nine stretch-sensitive PN afferents evenly distributed into the above four groups were studied. Rectal muscular afferents had significantly greater stretch-responses than the other three groups. Virtually all rectal afferents (98%) had low thresholds for response and encoded stimulus intensity into the noxious range without obvious saturation. Most colonic afferents (72%) also had low thresholds (<14 mmHg), but a significant proportion (28%) had high thresholds (>18 mmHg) for response. These high-threshold colonic afferents were sensitized to stretch by inflammatory soup; response threshold was significantly reduced (from 23 to 12 mmHg), and response magnitude significantly increased. These results suggest that the encoding of mechanosensory information differs between colonic and rectal stretch-sensitive PN afferents. Rectal afferents have a wide response range to stretch, whereas high-threshold colonic afferents likely contribute to visceral nociception. PMID:20075141

  4. Characterization of Mouse Lumbar Splanchnic and Pelvic Nerve Urinary Bladder Mechanosensory Afferents

    PubMed Central

    Xu, Linjing; Gebhart, G. F.

    2009-01-01

    Sensory information from the urinary bladder is conveyed via lumbar splanchnic (LSN) and sacral pelvic (PN) nerves to the spinal cord. In the present report we compared the mechanosensitive properties of single afferent fibers in these two pathways using an in vitro mouse bladder preparation. Mechanosensitive primary afferents were recorded from the LSN or PN and distinguished based on their response to receptive field stimulation with different mechanical stimuli: probing (160 mg to 2 g), stretch (1–25 g), and stroking of the urothelium (10–1,000 mg). Four different classes of afferent were recorded from the LSN and PN: serosal, muscular, muscular/urothielial, and urothelial. The LSN contained principally serosal and muscular afferents (97% of the total sample), whereas all four afferent classes of afferent were present in the PN (63% of which were muscular afferents). In addition, the respective proportions and receptive field distributions differed between the two pathways. Both low- and high-threshold stretch-sensitive muscular afferents were present in both pathways, and muscular afferents in the PN were shown to sensitize after exposure to an inflammatory soup cocktail. The LSN and PN pathways contain different populations of mechanosensitive afferents capable of detecting a range of mechanical stimuli and individually tuned to detect the type, magnitude, and duration of the stimulus. This knowledge broadens our understanding of the potential roles these two pathways play in conveying mechanical information from the bladder to the spinal cord. PMID:18003875

  5. Directional sensitivity of human periodontal mechanoreceptive afferents to forces applied to the teeth.

    PubMed Central

    Trulsson, M; Johansson, R S; Olsson, K A

    1992-01-01

    1. Single-unit impulse activity from thirty-eight mechanoreceptive afferent fibres was recorded in the human inferior alveolar nerve using tungsten microelectrodes. All afferents responded to mechanical stimulation of the teeth and most likely supplied periodontal mechanoreceptors. 2. All afferents showed their highest sensitivity to forces applied to a particular tooth (the lower incisors, the canine or the first premolar). Forces with 'ramp-and-hold' shaped profiles of similar magnitudes were applied to that tooth in the following six directions: lingual, labial, mesial and distal in the horizontal plane, and up and down in the axial direction of the tooth. Both static and dynamic response components were analysed. 3. All afferents were 'slowly adapting' since they discharged continuously in response to static forces in at least one stimulation direction. Twenty-five afferents (66%) were spontaneously active in the sense that they showed an on-going discharge in the absence of external stimulation. 4. Diverse receptive fields were observed. Most afferents (74%) responded to static forces in two or three of the four horizontal directions. Likewise, all units showed excitatory responses to axial loading with a majority (74%) responding in one of the two axial directions and the remainder in both axial directions. Spontaneously active afferents generally decreased their discharge rate when stimulated in directions opposite to the directions exciting the afferent. With regard to population responses, approximately half of the afferents showed excitatory responses to each stimulus direction except for downwards, in which 86% responded. 5. Twenty-three afferents (61%) exhibited the strongest response to forces in one of the horizontal directions. Of those, a majority were most responsive to the lingual direction (52%) and some to the labial direction (30%). Accordingly, the discharge rates during force application averaged over the whole afferent sample were highest in

  6. Pubertal changes in emotional information processing: pupillary, behavioral, and subjective evidence during emotional word identification.

    PubMed

    Silk, Jennifer S; Siegle, Greg J; Whalen, Diana J; Ostapenko, Laura J; Ladouceur, Cecile D; Dahl, Ronald E

    2009-01-01

    This study investigated pupillary and behavioral responses to an emotional word valence identification paradigm among 32 pre-/early pubertal and 34 mid-/late pubertal typically developing children and adolescents. Participants were asked to identify the valence of positive, negative, and neutral words while pupil dilation was assessed using an eyetracker. Mid-/late pubertal children showed greater peak pupillary reactivity to words presented during the emotional word identification task than pre-/early pubertal children, regardless of word valence. Mid-/late pubertal children also showed smaller sustained pupil dilation than pre-/early pubertal children after the word was no longer on screen. These findings were replicated controlling for participants' age. In addition, mid-/late pubertal children had faster reaction times to all words, and rated themselves as more emotional during their laboratory visit compared to pre-/early pubertal children. Greater recall of emotional words following the task was associated with mid-/late pubertal status, and greater recall of emotional words was also associated with higher peak pupil dilation. These results provide physiological, behavioral, and subjective evidence consistent with a model of puberty-specific changes in neurobehavioral systems underpinning emotional reactivity. PMID:19144220

  7. Asymmetric wavefront aberrations and pupillary shapes induced by electrical stimulation of ciliary nerve in cats measured with compact wavefront aberrometer.

    PubMed

    Miyagawa, Suguru; Mihashi, Toshifumi; Kanda, Hiroyuki; Hirohara, Yoko; Endo, Takao; Morimoto, Takeshi; Miyoshi, Tomomitsu; Fujikado, Takashi

    2014-01-01

    To investigate the changes in the wavefront aberrations and pupillary shape in response to electrical stimulation of the branches of the ciliary nerves in cats. Seven eyes of seven cats were studied under general anesthesia. Trains of monophasic pulses (current, 0.1 to 1.0 mA; duration, 0.5 ms/phase; frequency, 5 to 40 Hz) were applied to the lateral or medial branch of the short ciliary nerve near the posterior pole of the eye. A pair of electrodes was hooked onto one or both branch of the short ciliary nerve. The electrodes were placed about 5 mm from the scleral surface. The wavefront aberrations were recorded continuously for 2 seconds before, 8 seconds during, and for 20 seconds after the electrical stimulation. The pupillary images were simultaneously recorded during the stimulation period. Both the wavefront aberrations and the pupillary images were obtained 10 times/sec with a custom-built wavefront aberrometer. The maximum accommodative amplitude was 1.19 diopters (D) produced by electrical stimulation of the short ciliary nerves. The latency of the accommodative changes was very short, and the accommodative level gradually increased up to 4 seconds and reached a plateau. When only one branch of the ciliary nerve was stimulated, the pupil dilated asymmetrically, and the oblique astigmatism and one of the asymmetrical wavefront terms was also altered. Our results showed that the wavefront aberrations and pupillary dilations can be measured simultaneously and serially with a compact wavefront aberrometer. The asymmetric pupil dilation and asymmetric changes of the wavefront aberrations suggest that each branch of the ciliary nerve innervates specific segments of the ciliary muscle and dilator muscle of the pupil. PMID:25144536

  8. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    PubMed Central

    La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity. PMID:22268098

  9. In vitro Functional Characterization of Mouse Colorectal Afferent Endings

    PubMed Central

    Feng, Bin; Gebhart, G.F.

    2015-01-01

    This video demonstrates in detail an in vitro single-fiber electrophysiological recording protocol using a mouse colorectum-nerve preparation. The approach allows unbiased identification and functional characterization of individual colorectal afferents. Extracellular recordings of propagated action potentials (APs) that originate from one or a few afferent (i.e., single-fiber) receptive fields (RFs) in the colorectum are made from teased nerve fiber fascicles. The colorectum is removed with either the pelvic (PN) or lumbar splanchnic (LSN) nerve attached and opened longitudinally. The tissue is placed in a recording chamber, pinned flat and perfused with oxygenated Krebs solution. Focal electrical stimulation is used to locate the colorectal afferent endings, which are further tested by three distinct mechanical stimuli (blunt probing, mucosal stroking and circumferential stretch) to functionally categorize the afferents into five mechanosensitive classes. Endings responding to none of these mechanical stimuli are categorized as mechanically-insensitive afferents (MIAs). Both mechanosensitive and MIAs can be assessed for sensitization (i.e., enhanced response, reduced threshold, and/or acquisition of mechanosensitivity) by localized exposure of RFs to chemicals (e.g., inflammatory soup (IS), capsaicin, adenosine triphosphate (ATP)). We describe the equipment and colorectum–nerve recording preparation, harvest of colorectum with attached PN or LSN, identification of RFs in the colorectum, single-fiber recording from nerve fascicles, and localized application of chemicals to the RF. In addition, challenges of the preparation and application of standardized mechanical stimulation are also discussed. PMID:25651300

  10. Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats.

    PubMed

    Yang, Jian; Zhao, Jingbo; Chen, Pengmin; Nakaguchi, Toshiya; Grundy, David; Gregersen, Hans

    2016-03-15

    Partial intestinal obstruction causes smooth muscle hypertrophy, enteric neuronal plasticity, motility disorders, and biomechanical remodeling. In this study we characterized the stimulus-response function of afferent fibers innervating the partially obstructed jejunum. A key question is whether changes in afferent firing arise from remodeled mechanical tissue properties or from adaptive afferent processes. Partial obstruction was created by placing a polyethylene ring for 2 wk in jejunum of seven rats. Sham obstruction was made in six rats and seven rats served as normal controls. Firing from mesenteric afferent nerve bundles was recorded during mechanical ramp, relaxation, and creep tests. Stress-strain, spike rate increase ratio (SRIR), and firing rate in single units were assessed for evaluation of interdependency of the mechanical stimulations, histomorphometry data, and afferent nerve discharge. Partial intestinal obstruction resulted in hypertrophy and jejunal stiffening proximal to the obstruction site. Low SRIR at low strains during fast distension and at high stresses during slow distension was found in the obstructed rats. Single unit analysis showed increased proportion of mechanosensitive units but absent high-threshold (HT) units during slow stimulation, decreased number of HT units during fast stimulation, and shift from HT sensitivity towards low threshold sensitivity in the obstructed jejunum. Biomechanical remodeling and altered afferent response to mechanical stimulations were found in the obstructed jejunum. Afferents from obstructed jejunum preserved their function in encoding ongoing mechanical stimulation but showed changes in their responsiveness. The findings support that mechanical factors rather than adaption are important for afferent remodeling. PMID:26585414

  11. On the necessity of correcting peripheral target luminance for pupillary area

    SciTech Connect

    Bedell, H.E.; Katz, L.M.

    1982-10-01

    Despite the decrease in pupillary area for peripheral targets, retinal illuminance remains fairly constant to about 80 deg visual angle. Constant illuminance is maintained in the retinal periphery because the light that enters the pupil is concentrated into smaller retinal images. The correction of the peripheral target luminances for pupillary area is therefore unnecessary except under certain conditions.

  12. Abnormal pupillary light reflex with chromatic pupillometry in Gaucher disease.

    PubMed

    Narita, Aya; Shirai, Kentarou; Kubota, Norika; Takayama, Rumiko; Takahashi, Yukitoshi; Onuki, Takanori; Numakura, Chikahiko; Kato, Mitsuhiro; Hamada, Yusuke; Sakai, Norio; Ohno, Atsuko; Asami, Maya; Matsushita, Shoko; Hayashi, Anri; Kumada, Tomohiro; Fujii, Tatsuya; Horino, Asako; Inoue, Takeshi; Kuki, Ichiro; Asakawa, Ken; Ishikawa, Hitoshi; Ohno, Koyo; Nishimura, Yoko; Tamasaki, Akiko; Maegaki, Yoshihiro; Ohno, Kousaku

    2014-02-01

    The hallmark of neuronopathic Gaucher disease (GD) is oculomotor abnormalities, but ophthalmological assessment is difficult in uncooperative patients. Chromatic pupillometry is a quantitative method to assess the pupillary light reflex (PLR) with minimal patient cooperation. Thus, we investigated whether chromatic pupillometry could be useful for neurological evaluations in GD. In our neuronopathic GD patients, red light-induced PLR was markedly impaired, whereas blue light-induced PLR was relatively spared. In addition, patients with non-neuronopathic GD showed no abnormalities. These novel findings show that chromatic pupillometry is a convenient method to detect neurological signs and monitor the course of disease in neuronopathic GD. PMID:25356393

  13. Abnormal pupillary light reflex with chromatic pupillometry in Gaucher disease

    PubMed Central

    Narita, Aya; Shirai, Kentarou; Kubota, Norika; Takayama, Rumiko; Takahashi, Yukitoshi; Onuki, Takanori; Numakura, Chikahiko; Kato, Mitsuhiro; Hamada, Yusuke; Sakai, Norio; Ohno, Atsuko; Asami, Maya; Matsushita, Shoko; Hayashi, Anri; Kumada, Tomohiro; Fujii, Tatsuya; Horino, Asako; Inoue, Takeshi; Kuki, Ichiro; Asakawa, Ken; Ishikawa, Hitoshi; Ohno, Koyo; Nishimura, Yoko; Tamasaki, Akiko; Maegaki, Yoshihiro; Ohno, Kousaku

    2014-01-01

    The hallmark of neuronopathic Gaucher disease (GD) is oculomotor abnormalities, but ophthalmological assessment is difficult in uncooperative patients. Chromatic pupillometry is a quantitative method to assess the pupillary light reflex (PLR) with minimal patient cooperation. Thus, we investigated whether chromatic pupillometry could be useful for neurological evaluations in GD. In our neuronopathic GD patients, red light-induced PLR was markedly impaired, whereas blue light-induced PLR was relatively spared. In addition, patients with non-neuronopathic GD showed no abnormalities. These novel findings show that chromatic pupillometry is a convenient method to detect neurological signs and monitor the course of disease in neuronopathic GD. PMID:25356393

  14. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    PubMed

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  15. Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

    PubMed Central

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J.

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm−2 s−1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light. PMID:24797245

  16. Utricular afferents: morphology of peripheral terminals

    PubMed Central

    Huwe, J. A.; Logan, G. J.; Williams, B.; Rowe, M. H.

    2015-01-01

    The utricle provides critical information about spatiotemporal properties of head movement. It comprises multiple subdivisions whose functional roles are poorly understood. We previously identified four subdivisions in turtle utricle, based on hair bundle structure and mechanics, otoconial membrane structure and hair bundle coupling, and immunoreactivity to calcium-binding proteins. Here we ask whether these macular subdivisions are innervated by distinctive populations of afferents to help us understand the role each subdivision plays in signaling head movements. We quantified the morphology of 173 afferents and identified six afferent classes, which differ in structure and macular locus. Calyceal and dimorphic afferents innervate one striolar band. Bouton afferents innervate a second striolar band; they have elongated terminals and the thickest processes and axons of all bouton units. Bouton afferents in lateral (LES) and medial (MES) extrastriolae have small-diameter axons but differ in collecting area, bouton number, and hair cell contacts (LES >> MES). A fourth, distinctive population of bouton afferents supplies the juxtastriola. These results, combined with our earlier findings on utricular hair cells and the otoconial membrane, suggest the hypotheses that MES and calyceal afferents encode head movement direction with high spatial resolution and that MES afferents are well suited to signal three-dimensional head orientation and striolar afferents to signal head movement onset. PMID:25632074

  17. 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

  18. 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

  19. Determinants of Spatial and Temporal Coding by Semicircular Canal Afferents

    PubMed Central

    Highstein, Stephen M.; Rabbitt, Richard D.; Holstein, Gay R.; Boyle, Richard D.

    2010-01-01

    The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components—one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below. PMID:15845995

  20. A novel role for TRPM8 in visceral afferent function.

    PubMed

    Harrington, Andrea M; Hughes, Patrick A; Martin, Christopher M; Yang, Jing; Castro, Joel; Isaacs, Nicole J; Blackshaw, L Ashley; Brierley, Stuart M

    2011-07-01

    Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n=58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 μmol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P<.0001; n=37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 μmol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions. PMID:21489690

  1. Circadian variation in gastric vagal afferent mechanosensitivity.

    PubMed

    Kentish, Stephen J; Frisby, Claudine L; Kennaway, David J; Wittert, Gary A; Page, Amanda J

    2013-12-01

    Food intake is coordinated to cellular metabolism by clock gene expression with a master clock in the suprachiasmatic nucleus synchronized by light exposure. Gastric vagal afferents play a role in regulating food intake, but it is unknown whether they exhibit circadian variation in their mechanosensitivity. We aimed to determine whether gastric vagal afferents express clock genes and whether their response to mechanical stimuli oscillates throughout the light/dark cycle. Nodose ganglia were collected from 8-week-old female C57BL/6 mice every 3 h starting at lights off (1800 h) to quantify Bmal1, Per1, Per2, and Nr1d1 mRNA by qRT-PCR. Additionally in vitro single-fiber recordings of gastric vagal mechanoreceptors were taken at all time points. Per1, Per2, Bmal1, and Nr1d1 mRNA is expressed in the nodose ganglia and levels oscillated over a 24 h period. In mice fed ad libitum, gastric content was 3 times higher at 0000 h and 0300 h than 1200 h. The response of tension receptors to 3 g stretch was reduced by up to 70% at 2100 h, 0000 h, and 0300 h compared with 1200 h. Gastric mucosal receptor response to stroking with a 50 mg von Frey hair was 3 times greater at 1200 h and 1500 h than the response at 0000 h. Similar findings were obtained in mice fasted for 6 h or maintained in darkness for 3 d before study. Therefore, these changes do not result from food intake or the light/dark cycle. Thus, gastric vagal mechanoreceptors display circadian rhythm, which may act to control food intake differentially at different times of the day. PMID:24305819

  2. Fentanyl, an agonist at the mu opioid receptor, depresses pupillary unrest.

    PubMed

    Bokoch, Michael P; Behrends, Matthias; Neice, Andrew; Larson, Merlin D

    2015-05-01

    Pupillary unrest is a chaotic fluctuation in pupil size that is observed in darkness with the onset of drowsiness, and in ambient light. The mechanism of pupillary unrest in darkness as well as in ambient light is unknown but studies suggest that it is caused by fluctuating activity in the Edinger-Westphal (E.W.) nucleus. Neurons in the periaqueductal gray with oscillating firing patterns that are inhibitory to the E.W. nucleus have been described in the cat. We theorized that such oscillating neurons produce pupillary unrest in light and would be depressed by agents, such as opioids, known to depress inhibitory pathways in the midbrain. An infrared pupillometer was used to measure the effect of light on pupillary unrest in eight volunteer subjects, and on 20 patients scheduled for knee arthroscopy who received fentanyl as premedication. Pupillary unrest was quantified through spectral analysis of fast Fourier transforms. Sixteen-second measurements of pupil size at 33 Hz were filtered to eliminate blink artifacts and baseline drift. Pupillary unrest was augmented by excitation of the E.W. nucleus by light and was depressed by 40 ± 20% after the administration of the moderate dose of 1 mcg/kg of fentanyl. Recovery from the drug effect was observed. Based upon the data from this study we propose that pupillary unrest in light originates within oscillating inhibitory neurons that intermittently depress the E. W. nucleus. PMID:25737234

  3. Interleukin-1β sensitizes abdominal visceral afferents of cats to ischaemia and histamine

    PubMed Central

    Fu, Liang-Wu; Longhurst, John C

    1999-01-01

    Activation of abdominal splanchnic visceral afferents during mesenteric ischaemia induces visceral pain and evokes excitatory cardiovascular responses. Previous studies have shown that interleukin-1β (IL-1β) concentration is increased locally in tissues during ischaemia and reperfusion. Local administration of IL-1β sensitizes somatic afferents to mechanical, thermal and chemical stimulation. Therefore, we hypothesized that IL-1β stimulates or sensitizes splanchnic visceral afferents to ischaemia and to the action of chemical stimuli such as histamine. The concentration of IL-1β in mesenteric lymph and portal venous plasma in anaesthetized cats was measured with an enzyme-linked immunosorbent assay before, during and after 10 min of abdominal ischaemia. The level of IL-1β was significantly increased during ischaemia in lymph, but not in plasma. Discharge activity of single-unit abdominal visceral C fibre afferents was measured from the right thoracic sympathetic chain. Ischaemically sensitive C fibre afferents were identified according to their response to 5–10 min of abdominal ischaemia. Intra-arterial (i.a.) injection of a high dose of IL-1β (500 ng kg−1), but not of a lower dose (i.e. 15, 50 or 150 ng kg−1), stimulated most (six of seven) abdominal visceral afferents. IL-1β (15 ng kg−1, i.a.) significantly enhanced the increased activity of 11 of 13 C fibre afferents during 10 min of ischaemia. Conversely, an IL-1 type I receptor antagonist (IL-1ra, 1·5 μg kg−1, i.a.) significantly attenuated the increased activity in six of seven other C fibre afferents during ischaemia. IL-1β (15 ng kg−1, i.a.) significantly augmented the responses of 13 of 16 ischaemically sensitive abdominal afferents to histamine (5–10 μg kg−1, i.a.). Conversely, IL-1ra (1·5 μg kg−1, i.a.) significantly attenuated the responses of five of six other C fibre afferents to histamine. These data strongly suggest that stimulation of IL-1 type I receptors by IL-1

  4. Electrophysiological Properties of Dural Afferents in the Absence and Presence of Inflammatory Mediators

    PubMed Central

    Harriott, Andrea M.; Gold, Michael S.

    2009-01-01

    Migraine is a debilitating condition characterized by recurrent severe head pain. Although mechanisms underlying a migraine attack remain controversial, one proposal is that inflammatory mediator (IM)–induced activation and sensitization of dural afferents contribute to the initiation of migraine pain. We and others have shown that the electrophysiological properties of afferents, both in the absence and the presence of IM, vary as a function of target of innervation. These differences may account for unique aspects of pain syndromes associated with specific body regions. Therefore the purpose of the present study was to test the hypothesis that the electrophysiological properties of dural afferents differ from those innervating the temporalis muscle (TM), a structure in close proximity to the dura but that is not associated with pain syndromes at all similar to migraine. Acutely dissociated retrograde labeled primary afferents innervating the dura and TM were examined with whole cell current-clamp recordings. Passive and active electrophysiological properties were determined before and after the application of IM: (in μM) prostaglandin E2 (1), bradykinin (10), and histamine (1). In the absence of IM, there were significant differences between the two populations, particularly with respect to the response to suprathreshold stimulation where dural afferents were more excitable than TM afferents. Importantly, although both populations of afferents were sensitized by IM, the pattern of passive and active electrophysiological changes associated with IM-induced sensitization of these two populations of afferents suggested that there were both similarities and marked differences between the two with respect to underlying mechanisms of sensitization. If the differences between dural and TM afferents are due to a differential pattern of ion channel expression rather than differences in the relative density/biophysical properties of the same ion channels, it may be

  5. 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. PMID:21925651

  6. 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.

  7. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin

    PubMed Central

    Foss, Jason D.; Wainford, Richard D.; Engeland, William C.; Fink, Gregory D.

    2014-01-01

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats. PMID:25411365

  8. Functional specializations of primary auditory afferents on the Mauthner cells: interactions between membrane and synaptic properties.

    PubMed

    Curti, Sebastian; Pereda, Alberto E

    2010-01-01

    Primary auditory afferents are usually perceived as passive, timing-preserving, lines of communication. Contrasting this view, a special class of auditory afferents to teleost Mauthner cells, a command neuron that organizes tail-flip escape responses, undergoes potentiation of their mixed (electrical and chemical) synapses in response to high frequency cellular activity. This property is likely to represent a mechanism of input sensitization as these neurons provide the Mauthner cell with essential information for the initiation of an escape response. We review here the anatomical and physiological specializations of these identifiable auditory afferents. In particular, we discuss how their membrane and synaptic properties act in concert to more efficaciously activate the Mauthner cells. The striking functional specializations of these neurons suggest that primary auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized. PMID:19941953

  9. A role for the ciliary marginal zone in the melanopsin-dependent intrinsic pupillary light reflex.

    PubMed

    Semo, Ma'ayan; Gias, Carlos; Ahmado, Ahmad; Vugler, Anthony

    2014-02-01

    Maintenance of pupillary constriction in light-adapted rodents has traditionally been thought to involve a reflex between retina, brain and iris, with recent work identifying the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) as the major conduits for retinal input to the brain. There is also a less well-understood phenomenon whereby the iris of some mammals, including mice, will constrict to light when either the eye, or the iris itself is physically isolated from the brain. The intrinsic pupillary light reflex (iPLR) is the term given to pupil constriction in the absence of retinal input to the brain. Here, using an intraocular axotomy approach, we show that the iPLR in conscious mice spans a dynamic range over 3 log units of irradiance. This iPLR response is absent in melanopsin knockout (MKO) mice and can be significantly inhibited by atropine. Immunohistochemistry for cfos and melanopsin, in combination with light exposure revealed a population of small ipRGCs in the retinal ciliary marginal zone (CMZ), which remain responsive to light in axotomised mice. We report that damage to the CMZ in a novel in vitro preparation removes a significant component of the iPLR response, while a detailed immunohistochemical analysis of the CMZ in wildtype mice revealed a melanopsin-rich plexus, which was consistently most intense in nasal retina. There were clear examples of melanopsin-positive, direct retino-ciliary projections, which appear to emanate from Brn3b negative, M1 type ipRGCs. These cells are clustered along the melanopsin-rich plexus nasally and may channel ipRGC signals from retina into the iris via ciliary body. Comparison between wildtype and MKO mice reveals that the ciliary body is also weakly stained for melanopsin. Our results show that the full extent of iPLR in mice requires cholinergic neurotransmission and intact signalling at the CMZ/ciliary body. This response may be mediated to some extent by ipRGCs, which send

  10. Neck muscle afferents influence oromotor and cardiorespiratory brainstem neural circuits.

    PubMed

    Edwards, I J; Lall, V K; Paton, J F; Yanagawa, Y; Szabo, G; Deuchars, S A; Deuchars, J

    2015-01-01

    Sensory information arising from the upper neck is important in the reflex control of posture and eye position. It has also been linked to the autonomic control of the cardiovascular and respiratory systems. Whiplash associated disorders (WAD) and cervical dystonia, which involve disturbance to the neck region, can often present with abnormalities to the oromotor, respiratory and cardiovascular systems. We investigated the potential neural pathways underlying such symptoms. Simulating neck afferent activity by electrical stimulation of the second cervical nerve in a working heart brainstem preparation (WHBP) altered the pattern of central respiratory drive and increased perfusion pressure. Tracing central targets of these sensory afferents revealed projections to the intermedius nucleus of the medulla (InM). These anterogradely labelled afferents co-localised with parvalbumin and vesicular glutamate transporter 1 indicating that they are proprioceptive. Anterograde tracing from the InM identified projections to brain regions involved in respiratory, cardiovascular, postural and oro-facial behaviours--the neighbouring hypoglossal nucleus, facial and motor trigeminal nuclei, parabrachial nuclei, rostral and caudal ventrolateral medulla and nucleus ambiguus. In brain slices, electrical stimulation of afferent fibre tracts lateral to the cuneate nucleus monosynaptically excited InM neurones. Direct stimulation of the InM in the WHBP mimicked the response of second cervical nerve stimulation. These results provide evidence of pathways linking upper cervical sensory afferents with CNS areas involved in autonomic and oromotor control, via the InM. Disruption of these neuronal pathways could, therefore, explain the dysphagic and cardiorespiratory abnormalities which may accompany cervical dystonia and WAD. PMID:24595534

  11. Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut.

    PubMed

    Riley, T P; Neal-McKinney, J M; Buelow, D R; Konkel, M E; Simasko, S M

    2013-04-15

    Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first determined if selective lesions of capsaicin-sensitive vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) after mice were inoculated with either Campylobacter jejuni or Salmonella typhimurium. Our results demonstrate that the activation of nTS neurons by intraluminal pathogenic bacteria is dependent on intact, capsaicin sensitive vagal afferents. We next determined if inflammatory mediators could cause the observed increase in c-Fos expression in the nTS by a direct action on vagal afferents. This was tested by the use of single-cell calcium measurements in cultured vagal afferent neurons. We found that tumor necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) directly activate cultured vagal afferent neurons and that almost all TNFα and LPS responsive neurons were sensitive to capsaicin. We conclude that activation of the afferent arm of the parasympathetic neuroimmune reflex by pathogenic bacteria in the gut is dependent on capsaicin sensitive vagal afferent neurons and that the release of inflammatory mediators into intestinal tissue can be directly sensed by these neurons. PMID:23481698

  12. Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut

    PubMed Central

    Riley, T.P.; Neal-McKinney, J.M.; Buelow, D.R.; Konkel, M.E.; Simasko, S.M.

    2014-01-01

    Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first determined if selective lesions of capsaicin-sensitive vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) after mice were inoculated with either Campylobacter jejuni or Salmonella typhimurium. Our results demonstrate that the activation of nTS neurons by intraluminal pathogenic bacteria is dependent on intact, capsaicin sensitive vagal afferents. We next determined if inflammatory mediators could cause the observed increase in c-Fos expression in the nTS by a direct action on vagal afferents. This was tested by the use of single-cell calcium measurements in cultured vagal afferent neurons. We found that tumor necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) directly activate cultured vagal afferent neurons and that almost all TNFα and LPS responsive neurons were sensitive to capsaicin. We conclude that activation of the afferent arm of the parasympathetic neuroimmune reflex by pathogenic bacteria in the gut is dependent on capsaicin sensitive vagal afferent neurons and that the release of inflammatory mediators into intestinal tissue can be directly sensed by these neurons. PMID:23481698

  13. Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin.

    PubMed

    Peters, James H; Simasko, Steven M; Ritter, Robert C

    2006-11-30

    The gut-peptide, cholecystokinin (CCK), reduces food intake by acting at CCK-1 receptors on vagal afferent neurons, whereas the feeding effects of the adipokine hormone, leptin, are associated primarily with its action on receptors (ObRb) in the hypothalamus. Recently, however, ObRb mRNA has been reported in vagal afferent neurons, some of which also express CCK-1 receptor, suggesting that leptin, alone or in cooperation with CCK, might activate vagal afferent neurons, and influence food intake via a vagal route. To evaluate these possibilities we have been examining the cellular and behavioral effects of leptin and CCK on vagal afferent neurons. In cultured vagal afferent neurons leptin and CCK evoked short latency, transient depolarizations, often leading to action potentials, and increases in cytosolic calcium. There was a much higher prevalence of CCK and leptin sensitivity amongst cultured vagal afferent neurons that innervate stomach or duodenum than there was in the overall vagal afferent population. Furthermore, almost all leptin-responsive gastric and duodenal vagal afferents also were sensitive to CCK. Leptin, infused into the upper GI tract arterial supply, reduced meal size, and enhanced satiation evoked by CCK. These results indicate that vagal afferent neurons are activated by leptin, and that this activation is likely to participate in meal termination, perhaps by enhancing vagal sensitivity to CCK. Our findings are consistent with the view that leptin and CCK exert their influence on food intake by accessing multiple neural systems (viscerosensory, motivational, affective and motor) at multiple points along the neuroaxis. PMID:16872644

  14. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    PubMed

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  15. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

    PubMed Central

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-01-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  16. Neck afferent involvement in cardiovascular control during movement

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Ray, C. A.

    2000-01-01

    It is well established that labyrinth and neck afferent information contributes to the regulation of somatomotor function during movement and changes in posture. There is also convincing evidence that the vestibular system participates in the modulation of sympathetic outflow and cardiovascular function during changes in posture, presumably to prevent orthostatic hypotension. However, the labyrinth organs do not provide any signals concerning body movements with respect to the head. In contrast, the neck receptors, particularly muscle spindles, are well located and suited to provide information about changes in body position with respect to the head and vestibular signals. Studies in the cat suggest that neck afferent information may modulate the vestibulosympathetic reflex responses to head-neck movements. There is some evidence in the cat to suggest involvement of low threshold mechanoreceptors. However, human studies do not indicate that low threshold mechanoreceptors in the neck modulate cardiovascular responses. The human studies are consistent with the studies in the cat in that they demonstrate the importance of otolith activation in mediating cardiovascular and sympathetic responses to changes in posture. This paper briefly reviews the current experimental evidence concerning the involvement of neck afferent information in the modulation of cardiovascular control during movement and changes in posture.

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

    PubMed Central

    Rowe, Michael H.; Neiman, Alexander B.

    2011-01-01

    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; 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. PMID:21890114

  18. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse.

    PubMed

    Daly, Donna M; Park, Sung Jin; Valinsky, William C; Beyak, Michael J

    2011-06-01

    Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity. PMID:21486762

  19. Measurements of Pupillary Diameter and Wavefront Aberrations in Pregnant Women

    PubMed Central

    Altay, Mehmet Metin; Demirok, Gulizar; Balta, Ozgur; Bolu, Hulya

    2016-01-01

    Purpose. To show whether pregnancy affects the measurements of pupillary diameter and wavefront (WF) aberrations. Methods. This was a case-control study including 34 healthy pregnant women in the third trimester and age-matched 34 nonpregnant women. Only women who had no ocular abnormalities and no refractive error were included. We measured photopic and mesopic pupil diameter and WF aberrations at the third trimester and at the second postpartum month. Measurements of the right eyes were used in this study. The differences between groups were analysed by paired t-test and t-test. Results. Pregnant women's mean photopic pupil size in the third trimester was significantly higher than in postpartum period and in control group (3.74 ± 0.77, 3.45 ± 0.53, and 3.49 ± 0.15 mm, p < 0.05, resp.). Mesopic pupil size in the third trimester was also higher than in postpartum period and in control group (6.77 ± 0.52, 6.42 ± 0.55, and 6.38 ± 0.21 mm, p < 0.05, resp.). RMS-3 and RMS-5 values were higher in pregnancy but these differences were not statistically significant. Conclusion. Pregnancy increased photopic and mesopic pupil size significantly but did not increase wavefront aberrations notably. Increased pupil size may be due to increased sympathetic activity during pregnancy. And this activity can be noninvasively determined by measuring pupil size. PMID:26998383

  20. Visual acuity and pupillary reactions after peribulbar anaesthesia.

    PubMed Central

    Talks, S J; Chong, N H; Gibson, J M; Francis, I R

    1994-01-01

    The effect of peribulbar anaesthesia on optic nerve function in 20 patients, before and after cataract surgery, was measured. All the patients had decreased visual acuity. Five (25%) had no perception of light. Seventeen (85%) developed a relative afferent pupil defect (RAPD). No patients saw the operating instruments. Seven (35%) had improved visual acuity immediately postoperatively. Patients should be warned that they may lose vision completely on being given a peribulbar anaesthetic; however their vision will improve, but not necessarily immediately, postoperatively. Examination for an RAPD is a good method of providing reassurance that the operating instruments will not be seen. PMID:8110698

  1. 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. PMID:27040776

  2. Inflammation-induced plasticity of the afferent innervation of the airways.

    PubMed Central

    Carr, M J; Undem, B J

    2001-01-01

    The activation of primary afferent neurons that innervate the airways leads to homeostatic and defensive reflexes. The anatomic and physiologic characteristics of these afferent fibers do not appear to be static properties but rather appear to change rapidly in response to inflammation. The threshold for activation of airway afferent neurons to various stimuli, for example, is not fixed; these fibers can be become sensitized during inflammation. A subset of nociceptive-like (C-fibers) airway afferent neurons not only participates in centrally mediated reflexes but is also thought to release neuropeptides at their peripheral terminals, leading to neurogenic inflammation. An increase in the content of tachykinins is commonly seen in inflamed tissues, and there is accumulating evidence that irritation and inflammation of the airways is associated with the induction of tachykinin synthesis in non-nociceptive airway afferent fibers that under normal conditions do not contain neuropeptides. The release of neurokinins from the peripheral terminals in the airways and their central terminals in the brain stem may contribute to the symptoms of inflammatory airway diseases. Elevated release of neurokinins from peripheral terminals may promote local inflammatory responses, and the release of neurokinins in the brainstem, together with inflammation-induced increases in the excitability of afferent fibers, may culminate in altered visceral autonomic reflex activity, changes in breathing pattern, and cough. PMID:11544165

  3. Tram-Track Suture Technique for Pupillary Capture of a Scleral Fixated Intraocular Lens

    PubMed Central

    Kim, Sung In; Kim, Kiseok

    2016-01-01

    Purpose To report a new technique using tram-track suture for pupillary capture of a scleral fixated posterior chamber intraocular lens (PC-IOL) to reposition the tilted IOL. Methods In this prospective interventional case series, we describe a tram-track suture for pupillary capture of a scleral fixated PC-IOL. A long straight needle with double-armed 10-0 polypropylene is passed behind the iris and just above the optic portion (tilted forward) of the IOL. The other straight needle with double-armed 10-0 polypropylene is passed just below the optic portion (tilted backward) of the IOL. After the IOL is repositioned properly, the polypropylene sutures are gently pulled and tied. Results Four eyes of 4 patients underwent tram-track suture for pupillary capture of a scleral fixated PC-IOL. No intra- or postoperative complications were noted, and no pupillary captures were detected during the follow-up period. Conclusions The tram-track suture technique provides good centration and stability of a PC-IOL. This technique is an easy and effective way to reposition pupillary capture of an IOL. Further, it is also minimally invasive as it maintains a closed system. PMID:27462257

  4. Central pupillary light reflex circuits in the cat: II. Morphology, ultrastructure, and inputs of preganglionic motoneurons.

    PubMed

    Sun, Wensi; May, Paul J

    2014-12-15

    Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal, and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure, and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting that their activity may be modified by a variety of inputs. Furthermore, there were differences in the synaptic populations contacting the rostral vs. caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population, indicating that these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural, and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, whereas more caudal elements control the lens. PMID:24706263

  5. Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

    PubMed

    Halperin, Anthony; Pajuelo, Monica; Tornheim, Jeffrey A; Vu, Nancy; Carnero, Andrés M; Galdos-Cardenas, Gerson; Ferrufino, Lisbeth; Camacho, Marilyn; Justiniano, Juan; Colanzi, Rony; Bowman, Natalie M; Morris, Tiffany; MacDougall, Hamish; Bern, Caryn; Moore, Steven T; Gilman, Robert H

    2016-06-01

    Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients. PMID:27044564

  6. Central Pupillary Light Reflex Circuits in the Cat: II. Morphology, Ultrastructure and Inputs of Preganglionic Motoneurons

    PubMed Central

    Sun, Wensi; May, Paul J.

    2014-01-01

    Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting their activity may be modified by a variety of inputs. Furthermore, there were differences between the synaptic populations contacting the rostral and caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population indicating these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, while more caudal elements control the lens. PMID:24706263

  7. Vagal afferents, diaphragm fatigue, and inspiratory resistance in anesthetized dogs.

    PubMed

    Adams, J M; Farkas, G A; Rochester, D F

    1988-06-01

    This study tests three hypotheses regarding mechanisms that produce rapid shallow breathing during a severe inspiratory resistive load (IRL): 1) an intact vagal afferent pathway is necessary; 2) diaphragm fatigue contributes to tachypnea; and 3) hypoxia may alter the pattern of respiration. We imposed a severe IRL on pentobarbital sodium-anesthetized dogs, followed by bilateral vagotomy, then by supplemental O2. IRL alone produced rapid shallow breathing associated with hypercapnia and hypoxia. After the vagotomy, the breathing pattern became slow and deep, restoring arterial PCO2 but not arterial PO2 toward the control values. Relief of hypoxia had no effect, and at no time was there any evidence of fatigue of the diaphragm as measured by the response to phrenic nerve stimulation. We conclude that an intact afferent vagal pathway is necessary for the tachypnea resulting from a severe IRL, neither hypoxia nor diaphragm fatigue played a role, and, although we cannot rule out stimulation of vagal afferents, the simplest explanation for the increased frequency in our experiments is increased respiratory drive due to hypercapnia. PMID:3136122

  8. 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. PMID:2719524

  9. Acid-sensing by airway afferent nerves

    PubMed Central

    Lee, Lu-Yuan; Gu, Qihai; Xu, Fadi; Hong, Ju-Lun

    2013-01-01

    Inhalation of acid aerosol or aspiration of acid solution evokes a stimulatory effect on airway C-fiber and Aδ afferents, which in turn causes airway irritation and triggers an array of defense reflex responses (e.g., cough, reflex bronchoconstriction, etc.). Tissue acidosis can also occur locally in the respiratory tract as a result of ischemia or inflammation, such as in the airways of asthmatic patients during exacerbation. The action of proton on the airway sensory neurons is generated by activation of two different current species: a transient (rapidly activating and inactivating) current mediated through the acid-sensing ion channels, and a slowly activating and sustained current mediated through the transient receptor potential vanilloid type 1 (TRPV1) receptor. In view of the recent findings that the expression and/or sensitivity of TRPV1 are up-regulated in the airway sensory nerves during chronic inflammatory reaction, the proton-evoked irritant effects on these nerves may play an important part in the manifestation of various symptoms associated with airway inflammatory diseases. PMID:23524016

  10. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice

    PubMed Central

    Kentish, Stephen J.; Frisby, Claudine L.; Kritas, Stamatiki; Li, Hui; Hatzinikolas, George; O’Donnell, Tracey A.; Wittert, Gary A.; Page, Amanda J.

    2015-01-01

    Aim Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice. Methods TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined. Results Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet. Conclusion TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity. PMID:26285043

  11. Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons.

    PubMed

    Wu, Shaw-Wen; Lindberg, Jonathan E M; Peters, James H

    2016-05-01

    Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3(-/-1) mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID:26843581

  12. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1.

    PubMed

    Hofmann, Mackenzie E; Largent-Milnes, Tally M; Fawley, Jessica A; Andresen, Michael C

    2014-12-01

    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1- ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1- inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents. PMID:25185814

  13. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice

    PubMed Central

    La, Jun-Ho; Tanaka, Takahiro; Schwartz, Erica S.; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15–60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14–28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14–28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs. PMID:22859364

  14. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1

    PubMed Central

    Largent-Milnes, Tally M.; Fawley, Jessica A.; Andresen, Michael C.

    2014-01-01

    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1− ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1− inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents. PMID:25185814

  15. Pseudophacomorphic Glaucoma along with Pupillary Block after Visian™ Implantable Collamer Lens Implantation for High Myopia

    PubMed Central

    McCaughey, Michael V.; Mifflin, Thomas; Fenzl, Carlton R.; Goldsmith, Jason; Moshirfar, Majid

    2014-01-01

    Purpose To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL, STAAR Surgical) insertion. Methods A 44 year-old female with high myopia underwent bilateral ICL implantation of MICL12.6 after sulcus diameter measurements were performed by Pentacam. Results Pseudophacomorphic glaucoma-related angle closure occurred due to lens oversizing in the right eye. The mechanism was relieved via ICL explantation. In the left eye, pupillary block developed in a subacute manner after closure of the peripheral iridotomy (PI). The attack was ameliorated by reestablishing patency of the iridotomy. Conclusions ICL-related glaucomatous attacks may result from improper sizing as well as from placement of a single PI. Identification of the proper mechanism is vital as treatments differ significantly. In pseudophacomorphic glaucoma, explantation is needed. In pupillary block glaucoma, treatment involves establishment of a patent PI. PMID:25485179

  16. Enhancing the Early Differential Diagnosis of Plateau Iris and Pupillary Block Using A-Scan Ultrasonography

    PubMed Central

    Chen, Yu-Yen; Chu, Dachen; Chou, Pesus

    2015-01-01

    Purpose To distinguish the frequently misdiagnosed plateau iris eyes from pupillary block group and normal group, we compared the ocular biometrical parameters of them by A-scan ultrasongraphy. Methods In total, we retrospectively reviewed general characteristics and ocular findings including ocular biometric measurements of 71 normal, 39 plateau iris, and 83 pupillary block eyes. Results The normal controls, plateau iris group and pupillary block group were significantly different in age, but not in gender. The anterior chamber depth tended to decrease and the lens thickness tended to increase from normal to plateau iris to pupillary block eyes. Compared to those of plateau iris group, the pupillary block group had significantly shallower anterior chamber depth (2.90mm vs. 2.33mm; p<0.001), thicker lens (4.77mm vs. 5.11mm; p<0.001), shorter axial length (23.16mm vs. 22.63mm; p<0.001), smaller relative lens position (2.28 vs. 2.16; p<0.001) and larger lens/axial length factor (2.06 vs. 2.26; p<0.001). However, when comparing plateau iris and normal eyes, only axial length and lens/axial length factor were significantly different (23.16 vs. 23.54; p<0.05 and 2.06 vs. 1.96; p<0.05). Conclusions Measured by A-scan ultrasonography, the ocular biometrics of plateau iris were significantly different from those of pupillary block eyes. However, our A-scan ultrasongraphy generally found no significant biometric differences between plateau iris and normal eyes. These findings suggest that while A-scan ultrasonography might be used as a practical tool for differentiating plateau iris and papillary block eyes, a more meticulous gonioscopy and other assessments may be necessary to distinguish plateau iris from normal eyes. PMID:25689856

  17. 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

  18. Withdrawal and Restoration of Central Vagal Afferents Within the Dorsal Vagal Complex Following Subdiaphragmatic Vagotomy

    PubMed Central

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

    2014-01-01

    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. PMID:23749657

  19. 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

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

    PubMed

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

    2016-08-01

    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

  1. Vascular Endothelial Function and Blood Pressure Regulation in Afferent Autonomic Failure

    PubMed Central

    Jelani, Qurat-ul-ain; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2015-01-01

    BACKGROUND Familial dysautonomia (FD) is a rare hereditary disease characterized by loss of afferent autonomic neural fiber signaling and consequent profound impairment of arterial baroreflex function and blood pressure regulation. Whether vascular endothelial dysfunction contributes to defective vasomotor control in this form of afferent autonomic failure is not known. METHODS We assessed blood pressure response to orthostatic stress and vascular endothelial function with brachial artery reactivity testing in 34 FD subjects with afferent autonomic failure and 34 healthy control subjects. RESULTS Forty-four percent of the afferent autonomic failure subjects had uncontrolled hypertension at supine rest (median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144–155mm Hg; median diastolic blood pressure = 83mm Hg, IQR = 78–105mm Hg), and 88% had abnormal response to orthostatic stress (median decrease in systolic blood pressure after upright tilt = 48mm Hg, IQR = 29–61mm Hg). Flow-mediated brachial artery reactivity did not differ in subjects with afferent autonomic failure vs. healthy control subjects (median = 6.00%, IQR = 1.86–11.77%; vs. median = 6.27%, IQR = 4.65–9.34%; P = 0.75). In afferent autonomic failure subjects, brachial artery reactivity was not associated with resting blood pressure or the magnitude of orthostatic hypotension but was decreased in association with reduced glomerular filtration rate (r = 0.62; P < 0.001). CONCLUSIONS Brachial artery reactivity was preserved in subjects with afferent autonomic failure despite the presence of marked blood pressure dysregulation. Comorbid renal dysfunction was associated with reduced brachial artery reactivity. PMID:25128693

  2. PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions.

    PubMed

    Trottier, Greg; Hollenberg, Morley; Wang, Xuemei; Gui, Yu; Loutzenhiser, Kathy; Loutzenhiser, Rodger

    2002-05-01

    Proteinase-activated receptors (PARs) are a novel class of G protein-coupled receptors that respond to signals through endogenous proteinases. PAR activation involves enzymatic cleavage of the extracellular NH(2)-terminal domain and unmasking of a new NH(2) terminus, which serves as an anchored ligand to activate the receptor. At least four PAR subtypes have been identified. In the present study, we used the in vitro perfused hydronephrotic rat kidney to examine the effects of activating PAR-2 on the afferent arteriole. The synthetic peptide SLIGRL-NH(2), which corresponds to the exposed ligand sequence and selectively activates PAR-2, did not alter basal afferent arteriolar diameter but caused a concentration-dependent vasodilation (3-30 microM) of arterioles preconstricted by angiotensin II (0.1 nM). A modified peptide sequence (LSIGRL-NH(2), inactive at PAR-2) had no effect. This vasodilation was characterized by an initial transient component followed by a smaller sustained response. A similar pattern of vasodilation was seen when SLIGRL-NH(2) was administered to isolated perfused normal rat kidney. The sustained component of the PAR-2-induced afferent arteriolar vasodilation was eliminated by nitric oxide (NO) synthase inhibition (100 microM nitro-L-arginine methyl ester). In contrast, the transient vasodilation persisted under these conditions. This transient response was not observed when afferent arterioles were preconstricted with elevated KCl, suggesting involvement of an endothelium-derived hyperpolarizing factor. Finally, RT-PCR revealed the presence of PAR-2 mRNA in isolated afferent arterioles. These findings indicate that PAR-2 is expressed in the afferent arteriole and that its activation elicits afferent arteriolar vasodilation by NO-dependent and NO-independent mechanisms. PMID:11934700

  3. Atypical Pupillary Light Reflex and Heart Rate Variability in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Daluwatte, Chathuri; Miles, Judith H.; Christ, Shawn E.; Beversdorf, David Q.; Takahashi, T. Nicole; Yao, Gang

    2013-01-01

    We investigated pupillary light reflex (PLR) in 152 children with ASD, 116 typically developing (TD) children, and 36 children with non-ASD neurodevelopmental disorders (NDDs). Heart rate variability (HRV) was measured simultaneously to study potential impairments in the autonomic nervous system (ANS) associated with ASD. The results showed that…

  4. Abnormal Transient Pupillary Light Reflex in Individuals with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Fan, Xiaofei; Miles, Judith H.; Takahashi, Nicole; Yao, Gang

    2009-01-01

    Computerized binocular infrared pupillography was used to measure the transient pupillary light reflex (PLR) in both children with autism spectrum disorders (ASDs) and children with typical development. We found that participants with ASDs showed significantly longer PLR latency, smaller constriction amplitude and lower constriction velocity than…

  5. A new pupillarial scale insect (Hemiptera: Coccoidea: Eriococcidae) from Angophora in coastal New South Wales, Australia.

    PubMed

    Gullan, Penny J; Williams, Douglas J

    2016-01-01

    A new scale insect, Aolacoccus angophorae gen. nov. and sp. nov. (Eriococcidae), is described from the bark of Angophora (Myrtaceae) growing in the Sydney area of New South Wales, Australia. These insects do not produce honeydew, are not ant-tended and probably feed on cortical parenchyma. The adult female is pupillarial as it is retained within the cuticle of the penultimate (second) instar. The crawlers (mobile first-instar nymphs) emerge via a flap or operculum at the posterior end of the abdomen of the second-instar exuviae. The adult and second-instar females, second-instar male and first-instar nymph, as well as salient features of the apterous adult male, are described and illustrated. The adult female of this new taxon has some morphological similarities to females of the non-pupillarial palm scale Phoenicococcus marlatti Cockerell (Phoenicococcidae), the pupillarial palm scales (Halimococcidae) and some pupillarial genera of armoured scales (Diaspididae), but is related to other Australian Myrtaceae-feeding eriococcids. PMID:27395159

  6. Paraventricular nucleus is involved in the central pathway of adipose afferent reflex in rats.

    PubMed

    Shi, Zhen; Wang, Yuan-Fang; Wang, Gui-Hua; Wu, Yu-Long; Ma, Chun-Lei

    2016-05-01

    Increasing evidence indicates a link between sympathetic nervous system activation and obesity, but the underlying mechanisms remain elusive. The adipose afferent reflex (AAR) is a sympathoexcitatory reflex that is activated by afferent neurotransmission from the white adipose tissue (WAT). This study aimed to investigate whether the hypothalamic paraventricular nucleus (PVH) is an important component of the central neurocircuitry of the AAR. In anesthetized rats, the discharge activity of individual PVH neurons was recorded in vivo. Activation of WAT afferents was initiated by capsaicin injection, and the AAR was evaluated by monitoring renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses. The responses of PVH neurons to activation of WAT afferents were evaluated by c-fos immunoreactivity and the discharge activity of individual PVH neurons, which was recorded using extracellular single-unit recording. After activation of WAT afferents, both individual PVH neuron discharge activity and c-fos immunoreactivity increased. Bilateral selective lesions of the neurons in the PVH with kainic acid abolished the AAR. These results indicate that PVH is an important component of the central neurocircuitry of the AAR. PMID:26963333

  7. 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

  8. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract.

    PubMed

    Berthoud, H R; Blackshaw, L A; Brookes, S J H; Grundy, D

    2004-04-01

    Here we discuss the neuroanatomy of extrinsic gastrointestinal (GI) afferent neurones, the relationship between structure and function and the role of afferents in disease. Three pathways connect the gut to the central nervous system: vagal afferents signal mainly from upper GI regions, pelvic afferents mainly from the colorectal region and splanchnic afferents from throughout. Vagal afferents mediate reflex regulation of gut function and behaviour, operating mainly at physiological levels. There are two major functional classes - tension receptors, responding to muscular contraction and distension, and mucosal receptors. The function of vagal endings correlates well with their anatomy: tracing studies show intramuscular arrays (IMAs) and intraganglionic laminar endings (IGLEs); IGLEs are now known to respond to tension. Functional mucosal receptors correlate with endings traced to the lamina propria. Pelvic afferents serve similar functions to vagal afferents, and additionally mediate both innocuous and noxious sensations. Splanchnic afferents comprise mucosal and stretch-sensitive afferents with low thresholds in addition to high-threshold serosal/mesenteric afferents suggesting diverse roles. IGLEs, probably of pelvic origin, have been identified recently in the rectum and respond similarly to gastric vagal IGLEs. Gastrointestinal afferents may be sensitized or inhibited by chemical mediators released from several cell types. Whether functional changes have anatomical correlates is not known, but it is likely that they underlie diseases involving visceral hypersensitivity. PMID:15066001

  9. Xanthine oxidase, but not neutrophils, contributes to activation of cardiac sympathetic afferents during myocardial ischaemia in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Longhurst, John C

    2002-01-01

    Activation of cardiac sympathetic afferents during myocardial ischaemia causes angina and induces important cardiovascular reflex responses. Reactive oxygen species (ROS) are important chemical stimuli of cardiac afferents during and after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of production of hydroxyl radicals. Another potential source of these species is xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes (PMNs) also contribute to the production of ROS in some conditions. The present study tested the hypothesis that both xanthine oxidase-catalysed oxidation of purines and neutrophils provide a source of ROS sufficient to activate cardiac afferents during ischaemia. We recorded single-unit activity of cardiac afferents innervating the ventricles recorded from the left thoracic sympathetic chain (T1-5) of anaesthetized cats to identify the afferents' responses to ischaemia. The role of xanthine oxidase in activation of these afferents was determined by infusion of oxypurinol (10 mg kg−1, i.v.), an inhibitor of xanthine oxidase. The importance of neutrophils as a potential source of ROS in the activation of cardiac afferents during ischaemia was assessed by the infusion of a polyclonal antibody (3 mg ml−1 kg−1, i.v.) raised in rabbits immunized with cat PMNs. This antibody decreased the number of circulating PMNs and, to a smaller extent, platelets. Since previous data suggest that platelets release serotonin (5-HT), which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3 receptor) mechanism, before treatment with the antibody in another group, we blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 μg kg−1, i.v.). We observed that oxypurinol significantly decreased the activity of cardiac afferents during myocardial ischaemia from 1.5 ± 0.4 to 0.8 ± 0.4 impulses s−1. Similarly, the polyclonal antibody significantly reduced the discharge frequency of

  10. pH-evoked dural afferent signaling is mediated by ASIC3 and is sensitized by mast cell mediators

    PubMed Central

    Yan, Jin; Wei, Xiaomei; Bischoff, Christina; Edelmayer, Rebecca M.; Dussor, Gregory

    2013-01-01

    Background Prior studies have shown that decreased meningeal pH activates dural afferents via opening of acid-sensing ion channels (ASICs) suggesting one pathophysiological mechanism for the generation of headaches. The studies described here further examined the ASIC subtype mediating pH-induced dural-afferent activation and examined whether sensitization influences pH responses. Objective Given the potential importance of meningeal mast cells to headache, the goal of this study was to evaluate dural afferent responses to pH following sensitization with mast cell mediators. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with decreased pH alone or in combination with mast cell mediators. Trigeminal ganglion neurons retrogradely-labeled from the dura were stained with an ASIC3 antibody using immunohistochemistry. Currents and action potentials evoked by changes in pH alone or in combination with mast cell mediators were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. Results pH-sensitive dural afferents generated currents in response to the ASIC3 activator 2-guanidine-4-methylquinazoline (GMQ), approximately 80% of these neurons express ASIC3 protein, and pH-evoked behavioral responses were inhibited by the ASIC3 blocker APETx2. Following exposure to mast cell mediators, dural afferents exhibited increased pH-evoked excitability and cutaneous allodynia was observed at higher pH than with pH stimuli alone. Conclusion These data indicate that the predominant ASIC subtype responding to decreased meningeal pH is ASIC3. Additionally, they demonstrate that in the presence of inflammation, dural afferents respond to even smaller decreases in pH providing further support for the ability of small pH changes within the meninges to initiate afferent input leading to headache. PMID:23808707

  11. Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG

    PubMed Central

    Neeland, Melanie R; Elhay, Martin J; Powell, David R; Rossello, Fernando J; Meeusen, Els N T; de Veer, Michael J

    2015-01-01

    Vaccine formulations incorporating innate immune stimulants are highly immunogenic; however, the biological signals that originate in the peripheral tissues at the site of injection and are transmitted to the local lymph node to induce immunity remain unclear. By directly cannulating the ovine afferent lymphatic vessels, we have previously shown that it takes 72 hr for mature antigen-loaded dendritic cells and monocytes to appear within afferent lymph following injection of a liposomal formulation containing the Toll-like receptor ligand CpG. In this present study, we characterize the global transcriptional signatures at this time-point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72 hr post vaccination, liposomes alone induce no changes in gene expression and inflammatory profiles within afferent lymph; however, the incorporation of CpG drives interferon, antiviral and cytotoxic gene programmes. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination. PMID:25308816

  12. Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG.

    PubMed

    Neeland, Melanie R; Elhay, Martin J; Powell, David R; Rossello, Fernando J; Meeusen, Els N T; de Veer, Michael J

    2014-10-10

    Vaccine formulations incorporating innate immune stimulants are highly immunogenic, however the biological signals that originate in the peripheral tissues at the site of injection and are transmitted to the local lymph node to induce immunity remain unclear. By directly cannulating the ovine afferent lymphatic vessels, we have previously shown that it takes 72 hours for mature antigen-loaded dendritic cells and monocytes to appear within afferent lymph following injection of a liposomal formulation containing the TLR ligand CpG. In this present study, we characterise the global transcriptional signatures at this time point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72h post vaccination, liposomes alone induce no changes in gene expression and inflammatory profiles within afferent lymph; however the incorporation of CpG drives interferon, antiviral and cytotoxic gene programs. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination. This article is protected by copyright. All rights reserved. PMID:25308816

  13. A role for the outer retina in development of the intrinsic pupillary light reflex in mice.

    PubMed

    Vugler, A; Semo, M; Ortín-Martínez, A; Rojanasakul, A; Nommiste, B; Valiente-Soriano, F J; García-Ayuso, D; Coffey, P; Vidal-Sanz, M; Gias, C

    2015-02-12

    Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼ 30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the iPLR increased significantly in retinal degenerate mice >1.5 years of age. This was accompanied by an increase in baseline pupil tone in the dark to levels indistinguishable from those in adult wild types. This rejuvenated iPLR response was slowed by atropine application, suggesting the involvement of cholinergic neurotransmission. We could find no evidence of an increase in melanopsin expression by quantitative PCR in the iris and ciliary body of aged retinal degenerates and a detailed anatomical analysis revealed a significant decline in melanopsin-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in rdcl mice >1.5 years. Adult mice lacking rod function (Gnat1(-/-)) also had a weak iPLR, while mice lacking functional cones (Cpfl5) maintained a robust response. We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa. PMID:25433236

  14. 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. PMID:26082693

  15. Kv1 channels and neural processing in vestibular calyx afferents

    PubMed Central

    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. PMID:26082693

  16. An In Vitro Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

    PubMed Central

    Franco, Joy A.; Kloefkorn, Heidi E.; Hochman, Shawn; Wilkinson, Katherine A.

    2014-01-01

    Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice. PMID:25285602

  17. Naturalistic Stimuli Increase the Rate and Efficiency of Information Transmission by Primary Auditory Afferents

    NASA Astrophysics Data System (ADS)

    Rieke, F.; Bodnar, D. A.; Bialek, W.

    1995-12-01

    Natural sounds, especially communication sounds, have highly structured amplitude and phase spectra. We have quantified how structure in the amplitude spectrum of natural sounds affects coding in primary auditory afferents. Auditory afferents encode stimuli with naturalistic amplitude spectra dramatically better than broad-band stimuli (approximating white noise); the rate at which the spike train carries information about the stimulus is 2-6 times higher for naturalistic sounds. Furthermore, the information rates can reach 90% of the fundamental limit to information transmission set by the statistics of the spike response. These results indicate that the coding strategy of the auditory nerve is matched to the structure of natural sounds; this `tuning' allows afferent spike trains to provide higher processing centres with a more complete description of the sensory world.

  18. Reduced C-afferent fibre density affects perceived pleasantness and empathy for touch.

    PubMed

    Morrison, India; Löken, Line S; Minde, Jan; Wessberg, Johan; Perini, Irene; Nennesmo, Inger; Olausson, Håkan

    2011-04-01

    We examined patients with a heritable disorder associated with a mutation affecting the nerve growth factor beta gene. Their condition has been classified as hereditary sensory and autonomic neuropathy type V. Carriers of the mutation show a reduction in density of thin and unmyelinated nerve fibres, including C afferents. A distinct type of unmyelinated, low-threshold mechanoreceptive C fibre, the C-tactile afferent, is present in hairy but not glabrous skin of humans and other mammals. They have been implicated in the coding of pleasant, hedonic touch of the kind that occurs in affiliative social interactions. We addressed the relationship between C fibre function and pleasant touch perception in 10 individuals from a unique population of mutation carriers in Sweden. We also investigated the effect of reduced C-fibre density on patients' evaluation of observed interpersonal touch (empathy). Results showed that patients perceived gentle, slow arm stroking, optimal for eliciting C-tactile afferent responses (1-10  cm/s), as less pleasant than did matched controls and also differed in their rating patterns across stimulation velocities. Further, patients' blood-oxygen-level-dependent responses in posterior insular cortex--a target for C afferents--were not modulated by stimulation optimal for activating C-tactile afferents. Hence, perception of the hedonic aspect of dynamic touch likely depends on C-tactile afferent density. Closely similar patterns between individuals' ratings of felt and seen touch suggest that appraisal of others' touch is anchored in one's own perceptual experience, whether typical or atypical. PMID:21378097

  19. Pain processing by spinal microcircuits: afferent combinatorics.

    PubMed

    Prescott, Steven A; Ratté, Stéphanie

    2012-08-01

    Pain, itch, heat, cold, and touch represent different percepts arising from somatosensory input. How stimuli give rise to these percepts has been debated for over a century. Recent work supports the view that primary afferents are highly specialized to transduce and encode specific stimulus modalities. However, cross-modal interactions (e.g. inhibition or exacerbation of pain by touch) support convergence rather than specificity in central circuits. We outline how peripheral specialization together with central convergence could enable spinal microcircuits to combine inputs from distinctly specialized, co-activated afferents and to modulate the output signals thus formed through computations like normalization. These issues will be discussed alongside recent advances in our understanding of microcircuitry in the superficial dorsal horn. PMID:22409855

  20. 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…

  1. A binocular pupil model for simulation of relative afferent pupil defect, RAPD.

    PubMed

    Privitera, Claudio M; Stark, Lawrence W

    2004-01-01

    The human pupil is an important element studied in many clinical procedures. The binocular pupil model presented has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It simulates responses to the swinging flashlight test for different degrees of relative afferent pupil defects, RAPD. PMID:17271776

  2. Blockage of vibrissae afferents: I. Motor effects.

    PubMed

    Prchal, A; Albarracín, A L; Décima, E E

    2004-02-01

    In the past, it has been proposed that the rat vibrissae play an important role in other hand, postural abnormalities, muscle tone decreases and hypomotility after sensory organ destructions were proposed as evidence supporting the "level setting" or "tonic" hypothesis. This hypothesis postulates that afferent activity, besides its well know transductive functions, sets the excitability state of the central nervous system. We thought the vibrissal system to be a good model to dissect these two postulated roles because vibrissae trimming would annul the transductive function without affecting the integrity of nerve activity. Thus we compare the effects of trimming the whiskers with blocking the vibrissal afferent nerves on two types of motor behavior: activity in an open field and walking over a rope connecting two elevated platforms. We found that only vibrissal afferent blockage (both nerve section and local anaesthesia) produced severe failures in the motor performances studied. These effects could not be fully explained by the abolition of the vibrissae as a sensory modality because cutting the whiskers did not significantly affect the motor performance. These data are discussed in reference to a tonic or general excitatory function of sensory inputs upon the central nervous system. PMID:15143620

  3. rPLR: an imaging system for measuring pupillary light reflex at a distance

    PubMed Central

    Dinalankara, Dinalankara M. R.; Miles, Judith H.; Yao, Gang

    2015-01-01

    Pupillary light reflex (PLR) is a simple noninvasive neurological test that can reveal a great amount of information of the neural system. We report here a novel imaging system for measuring PLR without using any restraints to limit the subject’s movement. Our system incorporates a tracking component that can locate the subject’s eye position and redirect the pupillary imaging component to follow the subject’s movement. This system can measure PLR, at a distance from the subject, with high spatial resolution (<50 µm) and temporal resolution (120 Hz). Because this new PLR device can accommodate the subject’s movement, it is well positioned to test in young children and other people who have difficulty remaining voluntarily still during tests. PMID:25403005

  4. Interactions between visceral afferent signaling and stimulus processing

    PubMed Central

    Critchley, Hugo D.; Garfinkel, Sarah N.

    2015-01-01

    Visceral afferent signals to the brain influence thoughts, feelings and behavior. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated) physiological arousal to emotional, social and motivational behaviors, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain's representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed. PMID:26379481

  5. Cross-Modal Calibration of Vestibular Afference for Human Balance

    PubMed Central

    Héroux, Martin E; Law, Tammy C. Y.; Fitzpatrick, Richard C.; Blouin, Jean-Sébastien

    2015-01-01

    To determine how the vestibular sense controls balance, we used instantaneous head angular velocity to drive a galvanic vestibular stimulus so that afference would signal that head movement was faster or slower than actual. In effect, this changed vestibular afferent gain. This increased sway 4-fold when subjects (N = 8) stood without vision. However, after a 240 s conditioning period with stable balance achieved through reliable visual or somatosensory cues, sway returned to normal. An equivalent galvanic stimulus unrelated to sway (not driven by head motion) was equally destabilising but in this situation the conditioning period of stable balance did not reduce sway. Reflex muscle responses evoked by an independent, higher bandwidth vestibular stimulus were initially reduced in amplitude by the galvanic stimulus but returned to normal levels after the conditioning period, contrary to predictions that they would decrease after adaptation to increased sensory gain and increase after adaptation to decreased sensory gain. We conclude that an erroneous vestibular signal of head motion during standing has profound effects on balance control. If it is unrelated to current head motion, the CNS has no immediate mechanism of ignoring the vestibular signal to reduce its influence on destabilising balance. This result is inconsistent with sensory reweighting based on disturbances. The increase in sway with increased sensory gain is also inconsistent with a simple feedback model of vestibular reflex action. Thus, we propose that recalibration of a forward sensory model best explains the reinterpretation of an altered reafferent signal of head motion during stable balance. PMID:25894558

  6. Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

    PubMed

    Dhakal, Laxmi P; Sen, Ayan; Stanko, Carlene M; Rawal, Bhupendra; Heckman, Michael G; Hoyne, Jonathan B; Dimberg, Elliot L; Freeman, Michelle L; Ng, Lauren K; Rabinstein, Alejandro A; Freeman, William D

    2016-08-01

    Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved. PMID:27135180

  7. Enzyme replacement therapy delays pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis.

    PubMed

    Whiting, Rebecca E H; Narfström, Kristina; Yao, Gang; Pearce, Jacqueline W; Coates, Joan R; Castaner, Leilani J; Jensen, Cheryl A; Dougherty, Brittanie N; Vuillemenot, Brian R; Kennedy, Derek; O'Neill, Charles A; Katz, Martin L

    2014-08-01

    Late-infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a hereditary neurological disorder characterized by progressive retinal degeneration and vision loss, cognitive and motor decline, seizures, and pronounced brain atrophy. This fatal pediatric disease is caused by mutations in the CLN2 gene which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Utilizing a TPP1-/- Dachshund model of CLN2 disease, studies were conducted to assess the effects of TPP1 enzyme replacement administered directly to the CNS on disease progression. Recombinant human TPP1 (rhTPP1) or artificial cerebrospinal fluid vehicle was administered to CLN2-affected dogs via infusion into the CSF. Untreated and vehicle treated affected dogs exhibited progressive declines in pupillary light reflexes (PLRs) and electroretinographic (ERG) responses to light stimuli. Studies were undertaken to determine whether CSF administration of rhTPP1 alters progression of the PLR and ERG deficits in the canine model. rhTPP1 administration did not inhibit the decline in ERG responses, as rhTPP1 treated, vehicle treated, and untreated dogs all exhibited similar progressive and profound declines in ERG amplitudes. However, in some of the dogs treated with rhTPP1 there were substantial delays in the appearance and progression of PLR deficits compared with untreated or vehicle treated affected dogs. These findings indicate that CSF administration of TPP1 can attenuate functional impairment of neural pathways involved in mediating the PLR but does not prevent loss of retinal responses detectable with ERG. PMID:24954537

  8. Single tactile afferents outperform human subjects in a vibrotactile intensity discrimination task.

    PubMed

    Arabzadeh, Ehsan; Clifford, Colin W G; Harris, Justin A; Mahns, David A; Macefield, Vaughan G; Birznieks, Ingvars

    2014-11-15

    We simultaneously compared the sensitivity of single primary afferent neurons supplying the glabrous skin of the hand and the psychophysical amplitude discrimination thresholds in human subjects for a set of vibrotactile stimuli delivered to the receptive field. All recorded afferents had a dynamic range narrower than the range of amplitudes across which the subjects could discriminate. However, when the vibration amplitude was chosen to be within the steepest part of the afferent's stimulus-response function the response of single afferents, defined as the spike count over the vibration duration (500 ms), was often more sensitive in discriminating vibration amplitude than the perceptual judgment of the participants. We quantified how the neuronal performance depended on the integration window: for short windows the neuronal performance was inferior to the performance of the subject. The neuronal performance progressively improved with increasing spike count duration and reached a level significantly above that of the subjects when the integration window was 250 ms or longer. The superiority in performance of individual neurons over observers could reflect a nonoptimal integration window or be due to the presence of noise between the sensory periphery and the cortical decision stage. Additionally, it could indicate that the range of perceptual sensitivity comes at the cost of discrimination through pooling across neurons with different response functions. PMID:25143540

  9. Central Pupillary Light Reflex Circuits in the Cat: I. The Olivary Pretectal Nucleus

    PubMed Central

    Sun, Wensi; May, Paul J.

    2014-01-01

    The central pathways subserving the feline pupillary light reflex were examined by defining retinal input to the olivary pretectal nucleus (OPt), the midbrain projections of this nucleus, and the premotor neurons within it. Unilateral intravitreal wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) injections revealed differences in the pattern of retinal OPt termination on the two sides. Injections of WGA-HRP into OPt labeled terminals bilaterally in the anteromedian nucleus, and to a lesser extent in the supraoculomotor area, centrally projecting Edinger-Westphal nucleus and nucleus of the posterior commissure. Labeled terminals, as well as retrogradely labeled multipolar cells, were present in the contralateral OPt, indicating a commissural pathway. Injections of WGA-HRP into the anteromedian nucleus labeled fusiform premotor neurons within the OPt, as well as multipolar cells in the nucleus of the posterior commissure. Connections between retinal terminals and the pretectal premotor neurons were characterized by combining vitreous chamber and anteromedian nucleus injections of WGA-HRP in the same animal. Fusiform shaped, retrogradely labeled cells fell within the anterogradely labeled retinal terminal field in OPt. Ultrastructural analysis revealed labeled retinal terminals containing clear spherical vesicles. They contacted labeled pretectal premotor neurons via asymmetric synaptic densities. These results provide an anatomical substrate for the pupillary light reflex in the cat. Pretectal premotor neurons receive direct retinal input via synapses suggestive of an excitatory drive, and project directly to nuclei containing preganglionic motoneurons. These projections are concentrated in the anteromedian nucleus, indicating its involvement in the pupillary light reflex. PMID:24706328

  10. Characterization of silent afferents in the pelvic and splanchnic innervations of the mouse colorectum

    PubMed Central

    Gebhart, G. F.

    2011-01-01

    Hypersensitivity in inflammatory/irritable bowel syndrome is contributed to in part by changes in the receptive properties of colorectal afferent endings, likely including mechanically insensitive afferents (MIAs; silent afferents) that have the ability to acquire mechanosensitivity. The proportion and attributes of colorectal MIAs, however, have not previously been characterized. The distal ∼3 cm of colorectum with either pelvic (PN) or lumbar splanchnic (LSN) nerve attached was removed, opened longitudinally, pinned flat in a recording chamber, and perfused with oxygenated Krebs solution. Colorectal receptive endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. MIA endings were tested for response to and acquisition of mechanosensitivity by localized exposure to an inflammatory soup (IS). Colorectal afferents were also tested with twin-pulse and repetitive electrical stimulation paradigms. PN MIAs represented 23% of 211 afferents studied, 71% (30/42) of which acquired mechanosensitivity after application of IS to their receptive ending. LSN MIAs represented 33% of 156 afferents studied, only 23% (11/48) of which acquired mechanosensitivity after IS exposure. Mechanosensitive PN endings uniformly exhibited significant twin-pulse slowing whereas LSN endings showed no significant twin-pulse difference. PN MIAs displayed significantly greater activity-dependent slowing than LSN MIAs. In conclusion, significant proportions of MIAs are present in the colorectal innervation; significantly more in the PN than LSN acquire mechanosensitivity in an inflammatory environment. This knowledge contributes to our understanding of the possible roles of MIAs in colon-related disorders like inflammatory/irritable bowel syndrome. PMID:21071510

  11. Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy123

    PubMed Central

    Reyes, Beverly A. S.; Zitnik, Gerard; Foster, Celia; Van Bockstaele, Elisabeth J.

    2015-01-01

    Abstract Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident–intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies. PMID:26634226

  12. Afferent nipple valve malfunction caused by anchoring collar: an unexpected late complication of the Kock continent ileal reservoir.

    PubMed

    Arai, Y; Okada, Y; Matsuda, T; Hida, S; Takeuchi, H; Kihara, Y; Yoshida, O

    1991-01-01

    In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered. PMID:1984094

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

    PubMed

    Dickman, J D

    1996-09-01

    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

  14. 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

  15. Pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis.

    PubMed

    Whiting, Rebecca E H; Narfström, Kristina; Yao, Gang; Pearce, Jacqueline W; Coates, Joan R; Castaner, Leilani J; Katz, Martin L

    2013-11-01

    Late-infantile neuronal ceroid lipofuscinosis (CLN2) is a hereditary neurological disorder characterized by progressive retinal degeneration and vision loss, cognitive and motor decline, seizures, and pronounced brain atrophy. The progressive loss of neurological functions eventually leads to death, usually by the early teenage years. Utilizing a canine model of CLN2, therapeutic studies to inhibit the brain and retinal degenerations are currently under way. Using this dog model, studies were undertaken to compare quantitative assessments of the pupillary light reflex (PLR) and electroretinography (ERG) as tools for evaluating the effects of the disease on retinal function. The PLR and ERG were recorded in normal and CLN2-affected Dachshunds at 2 month intervals between the ages of 4 and 10 months. Using custom instrumentation for quantitative PLR assessments, a series of white light stimuli of varying intensity was used to elicit pupil constriction, and pupil images were recorded using continuous infrared illumination and an infrared-sensitive camera. Electroretinography was used to evaluate retinal function in the same dogs. As the disease progressed, affected dogs exhibited progressive and profound declines in ERG amplitudes under both scotopic and photopic conditions. With low intensity light stimuli, CLN2 was also accompanied by progressive deficits in the PLR. Changes in the PLR to dim light stimuli included significant deficits in latency, constriction velocity, constriction amplitude, and redilation velocity. However, despite the almost complete loss of detectable ERG responses by disease end stage, the PLR to bright stimuli was well preserved throughout the disease progression. These findings demonstrate that the PLR is much more sensitive than the ERG in detecting residual retinal function in animal models of retinal degenerative disease. The preservation of the PLR in dogs with profoundly depressed ERGs correlates with a preservation of visually

  16. Modeling the spinal pudendo-vesical reflex for bladder control by pudendal afferent stimulation.

    PubMed

    McGee, Meredith J; Grill, Warren M

    2016-06-01

    Electrical stimulation of the pudendal nerve (PN) is a promising approach to restore continence and micturition following bladder dysfunction resulting from neurological disease or injury. Although the pudendo-vesical reflex and its physiological properties are well established, there is limited understanding of the specific neural mechanisms that mediate this reflex. We sought to develop a computational model of the spinal neural network that governs the reflex bladder response to PN stimulation. We implemented and validated a neural network architecture based on previous neuroanatomical and electrophysiological studies. Using synaptically-connected integrate and fire model neurons, we created a network model with realistic spiking behavior. The model produced expected sacral parasympathetic nucleus (SPN) neuron firing rates from prescribed neural inputs and predicted bladder activation and inhibition with different frequencies of pudendal afferent stimulation. In addition, the model matched experimental results from previous studies of temporal patterns of pudendal afferent stimulation and selective pharmacological blockade of inhibitory neurons. The frequency- and pattern-dependent effects of pudendal afferent stimulation were determined by changes in firing rate of spinal interneurons, suggesting that neural network interactions at the lumbosacral level can mediate the bladder response to different frequencies or temporal patterns of pudendal afferent stimulation. Further, the anatomical structure of excitatory and inhibitory interneurons in the network model was necessary and sufficient to reproduce the critical features of the pudendo-vesical reflex, and this model may prove useful to guide development of novel, more effective electrical stimulation techniques for bladder control. PMID:26968615

  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. PMID:26926966

  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. Phrenic nerve afferent activation of neurons in the cat SI cerebral cortex.

    PubMed

    Davenport, Paul W; Reep, Roger L; Thompson, Floyd J

    2010-03-01

    Stimulation of respiratory afferents elicits neural activity in the somatosensory region of the cerebral cortex in humans and animals. Respiratory afferents have been stimulated with mechanical loads applied to breathing and electrical stimulation of respiratory nerves and muscles. It was hypothesized that stimulation of the phrenic nerve myelinated afferents will activate neurons in the 3a and 3b region of the somatosensory cortex. This was investigated in cats with electrical stimulation of the intrathoracic phrenic nerve and C(5) root of the phrenic nerve. The somatosensory cortical response to phrenic afferent stimulation was recorded from the cortical surface, contralateral to the phrenic nerve, ispilateral to the phrenic nerve and with microelectrodes inserted into the cortical site of the surface dipole. Short-latency, primary cortical evoked potentials (1 degrees CEP) were recorded with stimulation of myelinated afferents of the intrathoracic phrenic nerve in the contralateral post-cruciate gyrus of all animals (n = 42). The mean onset and peak latencies were 8.5 +/- 5.7 ms and 21.8 +/- 9.8 ms, respectively. The rostro-caudal surface location of the 1 degrees CEP was found between the rostral edge of the post-cruciate dimple (PCD) and the rostral edge of the ansate sulcus, medio-lateral location was between 2 mm lateral to the sagittal sulcus and the lateral end of the cruciate sulcus. Histological examination revealed that the 1 degrees CEP sites were recorded over areas 3a and 3b of the SI somatosensory cortex. Intracortical activation of 16 neurons with two patterns of neural activity was recorded: (1) short-latency, short-duration activation of neurons and (2) long-latency, long-duration activation of neurons. Short-latency neurons had a mean onset latency of 10.4 +/- 3.1 ms and mean burst duration of 10.1 +/- 3.2 ms. The short-latency units were recorded at an average depth of 1.7 +/- 0.5 mm below the cortical surface. The long-latency neurons had a

  20. The optics of the growing lungfish eye: lens shape, focal ratio and pupillary movements in Neoceratodus forsteri (Krefft, 1870).

    PubMed

    Bailes, Helena J; Trezise, Ann E O; Collin, Shaun P

    2007-01-01

    Lungfish (order Dipnoi) evolved during the Devonian period and are believed to be the closest living relatives to the land vertebrates. Here we describe the previously unknown morphology of the lungfish eye in order to examine ocular adaptations present in early sarcopterygian fish. Unlike many teleosts, the Australian lungfish Neoceratodus forsteri possesses a mobile pupil with a slow pupillary response similar to amphibians. The structure of the eye changes from juvenile to adult, with both eye and lens becoming more elliptical in shape with growth. This change in structure results in a decrease in focal ratio (the distance from lens center to the retina divided by the lens radius) and increased retinal illumination in adult fish. Despite a degree of lenticular correction for spherical aberration, there is considerable variation across the lens. A re-calculation of spatial resolving power using measured focal ratios from cryosectioning reveals a low ability to discriminate fine detail. The dipnoan eye shares more features with amphibian eyes than with most teleost eyes, which may echo the visual needs of this living fossil. PMID:17822577

  1. Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb.

    PubMed

    Khan, Serajul I; Burne, John A

    2010-01-13

    Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI <100 ms) resembling the inhibition seen in the voluntary EMG. This was consistent with the postsynaptic origin of cutaneous inhibition of the motoneurons. PMID:19850015

  2. Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity.

    PubMed

    Feng, Bin; Joyce, Sonali C; Gebhart, G F

    2016-05-15

    The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ∼25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1-10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonic-spiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain. PMID:26950857

  3. Spontaneous hyphema and pupillary block in a patient with a left ventricular assist device

    PubMed Central

    Kavoussi, Shaheen C.; Liu, Ji

    2015-01-01

    Summary The left ventricular assist device (LVAD) has been a standard of care for the management of patients with advanced heart failure since the 1990s. An increased risk of spontaneous bleeding related to the device has been noted, ranging from minor epistaxis to major thoracic and mediastinal hemorrhages. To our knowledge, intraocular hemorrhage has not been previously reported. We report a 72-year-old patient with an LVAD who subsequently developed a spontaneous intraocular hemorrhage that manifested as hyphema, pupillary block, and acute intraocular pressure elevation.

  4. Functional dopamine D2 receptors on rat vagal afferent neurones.

    PubMed Central

    Lawrence, A J; Krstew, E; Jarrott, B

    1995-01-01

    1. In the present study in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess dopamine D2 receptors. 2. Dopamine (10-300 microM) elicited a temperature- and concentration-dependent depolarization of the rat isolated nodose ganglion preparation. When applied to the tissue 15 min prior to agonist, raclopride (10 microM), clozapine (10 microM) or a mixture of raclopride and clozapine (10 microM each) all produced a threefold parallel shift to the right of the dopamine concentration-response curve. In contrast, SCH 23390 (100 nM), phentolamine and propranolol (1 microM each) failed to antagonize the dopamine-mediated depolarization. 3. [125I]-NCQ 298 (0.5 nM), a D2 selective radioligand, bound topographically to sections of rat brainstem. Densitometric quantification of autoradiograms revealed 93.8 +/- 0.5% specific binding of this salicylamide radioligand, as determined by raclopride (10 microM, n = 10 animals). Binding was highest in the nucleus tractus solitarius (NTS), particularly the medial and gelatinous subnuclei. In addition, specific binding was also observed in the interpolar spinal trigeminal nucleus and the inferior olive. 4. Unilateral nodose ganglionectomy caused a 36.6 +/- 3.0% reduction in specific binding in the denervated NTS compared to the contralateral NTS. Furthermore, the loss of binding was confined to the dorsal aspect of the medial subnucleus of the NTS. Sham surgery had no effect on the binding of [125I]-NCQ 298 in rat brainstem. 5. The present data provide evidence for the presence of functionally relevant dopamine D2 receptors on both the soma and central terminals of rat vagal afferent neurones.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 3 PMID:7606337

  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. PMID:25540101

  6. 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.

  7. Tracking the allocation of attention using human pupillary oscillations

    PubMed Central

    Naber, Marnix; Alvarez, George A.; Nakayama, Ken

    2013-01-01

    The muscles that control the pupil are richly innervated by the autonomic nervous system. While there are central pathways that drive pupil dilations in relation to arousal, there is no anatomical evidence that cortical centers involved with visual selective attention innervate the pupil. In this study, we show that such connections must exist. Specifically, we demonstrate a novel Pupil Frequency Tagging (PFT) method, where oscillatory changes in stimulus brightness over time are mirrored by pupil constrictions and dilations. We find that the luminance–induced pupil oscillations are enhanced when covert attention is directed to the flicker stimulus and when targets are correctly detected in an attentional tracking task. These results suggest that the amplitudes of pupil responses closely follow the allocation of focal visual attention and the encoding of stimuli. PFT provides a new opportunity to study top–down visual attention itself as well as identifying the pathways and mechanisms that support this unexpected phenomenon. PMID:24368904

  8. 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.

  9. 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

  10. Ginger and Its Pungent Constituents Non-Competitively Inhibit Serotonin Currents on Visceral Afferent Neurons

    PubMed Central

    Jin, Zhenhua; Lee, Goeun; Kim, Sojin; Park, Cheung-Seog; Park, Yong Seek

    2014-01-01

    Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons. PMID:24757377

  11. Ginger and its pungent constituents non-competitively inhibit serotonin currents on visceral afferent neurons.

    PubMed

    Jin, Zhenhua; Lee, Goeun; Kim, Sojin; Park, Cheung-Seog; Park, Yong Seek; Jin, Young-Ho

    2014-04-01

    Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons. PMID:24757377

  12. Spike Sorting of Muscle Spindle Afferent Nerve Activity Recorded with Thin-Film Intrafascicular Electrodes

    PubMed Central

    Djilas, Milan; Azevedo-Coste, Christine; Guiraud, David; Yoshida, Ken

    2010-01-01

    Afferent muscle spindle activity in response to passive muscle stretch was recorded in vivo using thin-film longitudinal intrafascicular electrodes. A neural spike detection and classification scheme was developed for the purpose of separating activity of primary and secondary muscle spindle afferents. The algorithm is based on the multiscale continuous wavelet transform using complex wavelets. The detection scheme outperforms the commonly used threshold detection, especially with recordings having low signal-to-noise ratio. Results of classification of units indicate that the developed classifier is able to isolate activity having linear relationship with muscle length, which is a step towards online model-based estimation of muscle length that can be used in a closed-loop functional electrical stimulation system with natural sensory feedback. PMID:20369071

  13. Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents

    PubMed Central

    Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.

    2011-01-01

    Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor α-3 (GFRα3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFRα3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFRα3 KO mice. The proportion of GFRα3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFRα3 KO mice. These findings suggest that enhanced GFRα3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

  14. Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons.

    PubMed

    Mifflin, S W

    1997-12-01

    Inspiratory hypoglossal motoneurons (IHMs) mediate contraction of the genioglossus muscle and contribute to the regulation of upper airway patency. Intracellular recordings were obtained from antidromically identified IHMs in anesthetized, vagotomized cats, and IHM responses to electrical activation of superior laryngeal nerve (SLN) afferent fibers at various frequencies and intensities were examined. SLN stimulus frequencies <2 Hz evoked an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence or only an IPSP in most IHMs that did not change in amplitude as the stimulus was maintained. During sustained stimulus frequencies of 5-10 Hz, there was a reduction in the amplitude of SLN-evoked IPSPs with time with variable changes in the EPSP. At stimulus frequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced over time. At a given stimulus frequency, increasing stimulus intensity enhanced the decay of the SLN-evoked postsynaptic potentials (PSPs). Frequency-dependent attenuation of SLN inputs to IHMs also occurred in newborn kittens. These results suggest that activation of SLN afferents evokes different PSP responses in IHMs depending on the stimulus frequency. At intermediate frequencies, inhibitory inputs are selectively filtered so that excitatory inputs predominate. At higher frequencies there was no discernible SLN-evoked PSP temporally locked to the SLN stimuli. Alterations in SLN-evoked PSPs could play a role in the coordination of genioglossal contraction during respiration, swallowing, and other complex motor acts where laryngeal afferents are activated. PMID:9390960

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

    PubMed Central

    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 (Iacid), as well as capsaicin-induced current (Icap). 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 Iacid parameters, but not in AP threshold, TTX-resistance, resting membrane potential, and Icap 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. PMID:27493509

  16. 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

  17. Pupil to limbus ratio: Introducing a simple objective measure using two-box method for measuring early anisocoria and progress of pupillary change in the ICU

    PubMed Central

    Mojumder, Deb Kumar; Patel, Saumil; Nugent, Kenneth; Detoledo, John; Kim, Jongyeol; Dar, Nabeel; Wilms, Henrik

    2015-01-01

    Introduction: Measurement of static pupillary size in the ICU is of importance in cases of acutely expanding intracranial mass lesions. The inaccuracies with subjective assessment of pupillary size by medical personnel preclude its use in emergent neurological situations. Objective: To determine if the ratio of pupil to limbus diameter (PLD ratio) measured by a two-box method is a reliable measure of pupil size for detecting early anisocoria and measuring pupillary changes. Materials and Methods: The PLD ratio was defined as the ratio of the pupillary diameter measured at a para-horizontal axial plane with the limbus diameter measured at the same or parallel axial plane. A two-box method was used to estimate the diameters of imaged pupils. Eyes were imaged using an iPhone 4S cellphone camera. Background illumination was measured and kept constant. The pupils of a 78-year-old woman, who presented with a large intra-axial parenchymal hemorrhage, were imaged. The patient had left pupillary miosis in dark but not in bright light. After presenting this case along with the images of the pupillary examination, a group of 21 medical staff were asked several questions on the pupillary examination. Reliability of PLD ratio were assessed via standard error of mean (S.E.M) of PLD ratios for 3 different subjects each imaged under constant illumination and fixation but from different angles to the optical axis. Results: Analysis of questionnaire data together with PLD ratios revealed that ~ 14% and 10% of participants could estimate the pupillary size in darkness and bright light respectively but none were simultaneously accurate indicating that subjective assessment of pupillary size was unreliable. The approach towards a systematic pupillary examination was inconsistent among the participants. The PLD ratio was found to be a reliable measure of pupillary size with standard error of mean below 0.1 mm for the three subjects tested. Conclusion: Static pupillary sizes can be

  18. Cortical projection of afferent information from tendon organs in the cat.

    PubMed Central

    McIntyre, A K; Proske, U; Rawson, J A

    1984-01-01

    In cats anaesthetized with chloralose, evidence has been sought for the projection of information from tendon organs to the sensory receiving areas of the cerebral cortex. Selective stimulation of afferent fibres from tendon organs has been achieved by raising the threshold to electrical stimulation of the fibres from primary endings of muscle spindles. The method uses longitudinal vibration at 200-250 Hz to elicit, over a period of 20 min, one impulse for each excursion of the vibrator from all of the spindles in the test muscle, soleus or medial gastrocnemius. The accumulated post-spike positivities following passage of the impulses are thought to be responsible for the rise in threshold. Segmental monosynaptic reflex testing after a bout of vibration was used to confirm that the residual Group I volley no longer contained impulses from muscle spindles. The volley in response to stimulating the nerve of the test muscle was timed to facilitate the monosynaptic reflex of a synergist. Before vibration 5- to 10-fold facilitation of reflex amplitude could be produced; however, after vibration, if all the spindle primary endings had been effectively engaged by the stimulus, no detectable facilitation remained. This test was found to be sensitive and reproducible. An afferent volley containing only activity of tendon organ afferents evoked small-amplitude potentials from the post-sigmoid gyrus of the contralateral pericruciate cortex. The field was highly localized and lay caudal to the main receiving area for activity from the sural nerve and from afferents of hip flexor muscles. Recordings with tungsten micro-electrodes revealed that the surface-evoked activity took origin in cellular discharges in the internal pyramidal layer of area 3a. Recent psychophysical experiments have provided evidence for a sense of muscle tension, as distinct from a sense of effort, and the tendon organ has been suggested as the likely receptor of origin. Our electrophysiological

  19. Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings

    PubMed Central

    Zhu, Yi; La, Jun-Ho; Wills, Zachary P.; Gebhart, G. F.

    2015-01-01

    Stretch-sensitive afferents comprise ∼33% of the pelvic nerve innervation of mouse colorectum, which are activated by colorectal distension and encode visceral nociception. Stretch-sensitive colorectal afferent endings respond tonically to stepped or ramped colorectal stretch, whereas dissociated colorectal dorsal root ganglion neurons generally fail to spike repetitively upon stepped current stimulation. The present study investigated this difference in the neural encoding characteristics between the soma and afferent ending using pharmacological approaches in an in vitro mouse colon-nerve preparation and complementary computational simulations. Immunohistological staining and Western blots revealed the presence of voltage-gated sodium channel (NaV) 1.6 and NaV1.7 at sensory neuronal endings in mouse colorectal tissue. Responses of stretch-sensitive colorectal afferent endings were significantly reduced by targeting NaV1.6 using selective antagonists (μ-conotoxin GIIIa and μ-conotoxin PIIIa) or tetrodotoxin. In contrast, neither selective NaV1.8 (A803467) nor NaV1.7 (ProTX-II) antagonists attenuated afferent responses to stretch. Computational simulation of a colorectal afferent ending that incorporated independent Markov models for NaV1.6 and NaV1.7, respectively, recapitulated the experimental findings, suggesting a necessary role for NaV1.6 in encoding tonic spiking by stretch-sensitive afferents. In addition, computational simulation of a dorsal root ganglion soma showed that, by adding a NaV1.6 conductance, a single-spiking neuron was converted into a tonic spiking one. These results suggest a mechanism/channel to explain the difference in neural encoding characteristics between afferent somata and sensory endings, likely caused by differential expression of ion channels (e.g., NaV1.6) at different parts of the neuron. PMID:25652923

  20. Quantitative assessment of pupillary light reflex in normal and anesthetized dogs: a preliminary study.

    PubMed

    Kim, Jury; Heo, Jiseong; Ji, Dongbeom; Kim, Min-Su

    2015-04-01

    The purpose of this study was to quantitatively assess the pupillary light reflex (PLR) in normal and anesthetized dogs using a pupillometer. Eleven dogs (20 eyes) of various breeds were included. PLRs were measured with a handheld pupillometer in dim light before and during anesthesia. Anesthesia was conducted with atropine, xylazine and ketamine. Parameters of pupillometry included neurological pupil index (NPi), pupil size, percent of change (%CH), latency (LAT), constriction velocity (CV), maximum constriction velocity (MCV) and dilation velocity (DV). NPi,%CH, CV and MCV were significantly decreased during anesthesia compared with the pre-anesthesia data. The results suggest that atropine-xylazine-ketamine combination anesthesia depresses the PLR. Additionally, this study demonstrates the feasibility of the use of a pupillometer in dogs. PMID:25648149

  1. Tbr2 is required to generate a neural circuit mediating the pupillary light reflex.

    PubMed

    Sweeney, Neal T; Tierney, Hannah; Feldheim, David A

    2014-04-16

    There are ∼20 types of retinal ganglion cells (RGCs) in mice, each of which has distinct molecular, morphological, and physiological characteristics. Each RGC type sends axon projections to specific brain areas that execute light-dependent behaviors. Here, we show that the T-box transcription factor Tbr2 is required for the development of several RGC types that participate in non-image-forming circuits. These types are molecularly distinct, project to non-image-forming targets, and include intrinsically photosensitive RGCs. Tbr2 mutant mice have reduced retinal projections to non-image-forming nuclei and an attenuated pupillary light reflex. These data demonstrate that Tbr2 acts to execute RGC type choice and/or survival in a set of RGCs that mediates light-induced subconscious behaviors. PMID:24741035

  2. Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders

    PubMed Central

    Miles, J H; Sun, J; Yao, G

    2014-01-01

    Atypical pupillary light reflexes (PLR) has been observed in children with autism spectrum disorders (ASD), which suggests potential autonomic nervous system (ANS) dysfunction in ASD. ANS is also involved in modulating sensory processing and sensory dysfunction has been widely reported in children with ASD. However, the potential association between physiological measurements of PLR and behavioral observations (e.g. sensory behaviors) has not been examined extensively in literature. In this study, we investigated the potential correlation between PLR and frequently observed sensory behaviors in children with ASD. We found a significant association between PLR constriction amplitude and a set of sensory behaviors in the ASD group but not in typically developing children. Children with ASD who showed more atypical sensory behaviors also had smaller PLR constriction amplitudes. A smaller PLR constriction amplitude suggests lower parasympathetic modulation. This observation implies that some atypical sensory behaviors in children with ASD could be associated with decreased parasympathetic modulation. PMID:25528080

  3. Reverse pupillary block associated with pigment dispersion syndrome after in-the-bag intraocular lens implantation.

    PubMed

    Itagaki, Hideo; Kunikata, Toshio; Hiratsuka, Kentaro; Saito, Junichiro; Oshika, Tetsuro

    2013-12-01

    A 61-year-old man with high myopia who had received a systemic α1A-adrenoceptor antagonist had phacoemulsification and in-the-bag intraocular lens implantation in the right eye. One day postoperatively, marked pigment dispersion in the anterior chamber, posterior bowing of the iris, and iridodonesis were noted associated with a subsequent elevation in intraocular pressure (IOP). Pharmacological pupil dilation was effective in reducing pigment dispersion and IOP, and laser peripheral iridotomy was performed to alleviate posterior bowing of the iris. We hypothesize that dynamic changes in the aqueous humor flow by cataract surgery and latent flaccidity of the iris due to the systemic α1A-adrenoceptor antagonist caused reverse pupillary block. High myopia may be another risk factor for this complication. PMID:24140374

  4. The effect of pharmacologic pupillary dilatation on anterior segment parameters in patients with exfoliation syndrome

    PubMed Central

    Mocan, Mehmet Cem; Ustunel, Saim; Dikmetas, Ozlem; Bozkurt, Banu; Irkec, Murat

    2013-01-01

    Purpose The purpose of this study was to evaluate the effect of pharmacologic pupillary dilatation on anterior chamber depth (ACD) and anterior chamber angle (ACA) in eyes with exfoliation syndrome (XFS). Methods Thirty-six eyes of 36 patients with XFS were evaluated with slit-lamp examination, Goldmann applanation tonometry and ultrasound biomicroscopy (UBM) under standard light conditions. Primary outcome parameters were defined as the change in ACD and ACA measured before and 40 min after instillation of a single drop of either 1% cyclopentolate (Group I; n = 12), 2.5% phenylephrine (Group II; n = 12) or 1% tropicamide (Group III; n = 12). Change in intraocular pressure (IOP) during the same time interval was included as a secondary outcome measure. Results The average predilatation ACD, ACA and IOP values in the study subjects were 2.54 ± 0.40 mm, 27.9 ± 6.3° and 14.9 ± 3.1 mmHg, respectively. There were no significant differences in the mean age (p = 0.461), the female/male ratio (p = 0.232), baseline ACD (p = 0.841), ACA (p = 0.761) or IOP (p = 0.070) within the three groups. Differences in dilation induced changes in ACD (p = 0.108), ACA (p = 0.636) and IOP (p = 0.160) between the three groups were not statistically significant. Conclusion Pupillary dilatation with a single drop of 1.0% cyclopentolate, 2.5% phenylephrine or 1% tropicamide is not associated with shallowing of the anterior chamber or narrowing of the ACA in patients with XFS who present with open angles. PMID:24646901

  5. Prolonged physiological reactivity and loss: Association of pupillary reactivity with negative thinking and feelings.

    PubMed

    Siegle, Greg J; D'Andrea, Wendy; Jones, Neil; Hallquist, Michael N; Stepp, Stephanie D; Fortunato, Andrea; Morse, Jennifer Q; Pilkonis, Paul A

    2015-11-01

    Prolonged psychophysiological reactions to negative information have long been associated with negative thinking and feeling. This association is operationalized in the RDoC negative affect construct of loss, which is nominally indexed by prolonged physiological reactivity, cognitive loss-related constructs such as rumination and guilt, and more feeling-related constructs such as sadness, crying, and anhedonia. These associations have not been tested explicitly. If thinking and feeling aspects of loss reflect different physiological mechanisms, as might be suggested by their putative neurobiology, different intervention pathways might be suggested. Here we examined the extent to which self-reported negative thinking and feeling constructs were associated with prolonged pupillary reactivity following negative words and a subsequent cognitive distractor in a diverse heterogeneously diagnosed sample of N=84 participants. We also considered indices of abuse and variables associated with borderline personality disorder as possible moderators. Consistently, feeling-related negative affect constructs were related to prolonged pupillary reactivity during the distractor after a negative stimulus whereas thinking-related constructs were not. These data suggest that people who have sustained physiological reactions to emotional stimuli may be more strongly characterized by non-linguistic negative feelings than explicit cognitions related to loss. Sustained physiological reactions could reflect efforts to regulate feeling states. In contrast to cognitive and affective variables, abuse was associated with decreased physiological reactivity, consistent with decreased neural engagement. Interventions that target mechanisms underlying feelings and their regulation may be more mechanistically specific to sustained reactivity than those which directly address cognitions. PMID:26143740

  6. 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

  7. 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.

  8. Contribution of vagal afferents to respiratory reflexes evoked by acute inhalation of ozone in dogs

    SciTech Connect

    Schelegle, E.S.; Carl, M.L.; Coleridge, H.M.; Coleridge, J.C.; Green, J.F. )

    1993-05-01

    Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40-70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.

  9. Modification by previous afferent discharge of the adaptation of frog muscle spindles following an extension.

    PubMed Central

    Brokensha, G; Westbury, D R

    1978-01-01

    1. Extension of a frog muscle spindle evoked a discharge of impulses in its sensory axon. The adaptation of the discharge after the dynamic phase of stretching occurred in two phases. At first the impulse train was almost regular and adapted quickly, but later this gave place to a phase of slower adaptation in which the variability of discharge was much increased. 2. The discharge of action potentials by the muscle spindle depressed the response of the receptor to a subsequent extension. This was true whether they were elicited antidromically by afferent stimulation or orthodromically by longitudinal vibration. This depression had its most marked effect on the first phase of adaptation where it greatly increased the rate of adaptation. The second, slower, phase of adaptation was little influenced. 3. The depression increased with the duration and with the frequency of afferent stimulation. It persisted for about 300 msec. 4. The results show that the properties of the spike generating mechanisms in the muscle spindle are modified by previous discharge and that this modification may influence the overall properties of the receptor. 5. The fact that afferent stimulation has different effects on the two phases of adaptation is consistent with the suggestion that the impulse train evoked by extension is derived from more than one spike generator within the muscle spindle. PMID:146734

  10. Morphology of single primary spindle afferents of the intercostal muscles in the cat.

    PubMed

    Nakayama, K; Niwa, M; Sasaki, S I; Ichikawa, T; Hirai, N

    1998-09-01

    A reconstruction was made of the trajectory of primary spindle afferents from the intercostal muscles in the spinal cord of the cat. Intraaxonal recordings were performed from the primary spindle afferents that were identified by their response to lung inflation and stimulus threshold to activate the action potentials. The afferents were stained by using intraaxonal injection of horseradish peroxidase (HRP). Results were obtained mainly from internal intercostal Ia fibers, which entered the spinal cord and bifurcated into ascending and descending branches. The ascending branches could be traced up to 10.7 mm, and the descending branches could be traced up to 7.3 mm. The ascending branches extended to the next segment. Collaterals ranging from one to six were given off from these branches. The distances between adjacent collaterals ranged from 0.9 mm to 4.7 mm. Each collateral had similar morphological characteristics. The collaterals entered the dorsal horn and ran toward lamina IX through the medial half of the gray matter. Fine branches and boutons were given off in laminae V, VII, VIII, and IX. The aggregations of these branches were found in lamina VII, mainly in the region of Clarke's column and in the ventral and ventrolateral regions thereof and in lamina IX, mainly in the nucleus lateromedialis. Most terminals did not contact the somata of target neurons in all laminae in which terminals were found. However, a few terminals were found to contact large neurons in lamina IX. In addition to these aggregates, there were some terminals scattered throughout the ventral horn. Thus, it was concluded that single intercostal Ia afferents project to the region of Clarke's column, to the intercostal motor nucleus, and to the intermediate regions. PMID:9717703

  11. Afferent Arteriolar Dilation to 11,12-EET Analogs Involves PP2A Activity and Ca2+-Activated K+ Channels

    PubMed Central

    Imig, John D.; Dimitropoulou, Christiana; Reddy, D. Sudarshan; White, Richard E.; Falck, John R.

    2008-01-01

    The epoxygenase metabolite, 11,12-epoxyeicosatrienoic acid (11,12-EET), has renal vascular actions. 11,12-EET analogs have been developed to determine the structure activity relationship for 11,12-EET and as a tool to investigate signaling mechanisms responsible for afferent arteriolar dilation. We hypothesized that 11,12-EET mediated afferent arteriolar dilation involves increased phosphoprotein phosphatase 2A (PP2A) and large-conductance calcium activated K+ (KCa) channels. We evaluated the chemically and/or metabolically stable 11,12-EET analogs: 11,12-EET-N-methylsulfonimide (11,12-EET-SI), 11-nonyloxy-undec-8(Z)-enoic acid (11,12-ether-EET-8-ZE), and 11,12-trans-oxidoeicosa-8(Z)-eonoic acid (11,12-tetra-EET-8-ZE). Afferent arteriolar responses were assessed. Activation of KCa channels by 11,12-EET analogs were established by single cell channel recordings in renal myocytes. Assessment of renal vascular responses revealed that 11,12-EET analogs increased afferent arteriolar diameter. Vasodilator responses to 11,12-EET analogs were abolished by K+ channel or PP2A inhibition. 11,12-EET analogs activated renal myocyte large-conductance KCa channels. 11,12-EET analogs increased cAMP by 2-fold and PP2A activity increased 3-8 fold in renal myocytes. PP2A inhibition did not significantly affect the 11,12-EET analog mediated increase in cAMP and PP2A increased renal myocyte KCa channel activity to a much greater extent than PKA. These data support the concept that 11,12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole. PMID:18260004

  12. 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).

  13. 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

  14. Afferent hypersensitivity in a mouse model of post-inflammatory gut dysfunction: role of altered serotonin metabolism

    PubMed Central

    Keating, Christopher; Beyak, Michael; Foley, Stephen; Singh, Gulzar; Marsden, Charles; Spiller, Robin; Grundy, David

    2008-01-01

    Visceral hypersensitivity is an important clinical feature associated with irritable bowel syndrome which in some patients has been linked to prior infection. Here we employ an animal model in which transient infection leads to persistent gut dysfunction to investigate the role of altered 5-HT metabolism upon afferent mechanosensensitivity in the post-infected gut. Jejunal segments isolated from Trichinella spiralis-infected mice were used to assess 5-HT metabolism whilst afferent activity in T. spiralis-infected mice was studied by extracellular recordings from jejunal mesenteric afferent bundles and patch clamp recordings of isolated nodose ganglion neurons (NGNs). During acute infection, intestinal 5-HT content and release increased, 5-HT turnover decreased and afferent discharge in response to mechanical stimulation was attenuated. By day 28 post infection (PI), 5-HT turnover had normalized, but 5-HT content and release were still elevated. This was associated with afferent mechano-hypersensitivity, which persisted for 8 weeks PI and was susceptible to 5-HT3 receptor blockade. NGNs from post-infected animals were more excitable than controls but their current densities in response to 2-methyl-5-HT were lower. T. spiralis infection increased mucosal 5-HT bioavailability and affected the spontaneous activity and mechanosensitivity of gastrointestinal sensory nerves. This involved an initial hyposensitivity occurring during acute infection followed by long-term hypersensitivity in the post-infectious period that was in part mediated by 5-HT acting via 5-HT3 receptors. Functional down-regulation of 5-HT3 receptors also occurs in the post-infected animals, which may represent an adaptive response to increased mucosal 5-HT bioavailability. PMID:18653657

  15. Histaminergic afferent system in the cerebellum: structure and function.

    PubMed

    Li, Bin; Zhu, Jing-Ning; Wang, Jian-Jun

    2014-01-01

    Histaminergic afferent system of the cerebellum, having been considered as an essential component of the direct hypothalamocerebellar circuits, originates from the tuberomammillary nucleus in the hypothalamus. Unlike the mossy fibers and climbing fibers, the histaminergic afferent fibers, a third type of cerebellar afferents, extend fine varicose fibers throughout the cerebellar cortex and nuclei. Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum. Through these histamine receptors, histamine directly excites Purkinje cells and granule cells in the cerebellar cortex, as well as the cerebellar nuclear neurons. Therefore, the histaminergic afferents parallelly modulate these dominant components in the cerebellar circuitry and consequently influence the final output of the cerebellum. In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions. Accordingly, histaminergic reagents may become potential drugs for clinical treatment of cerebellar ataxia and other cerebellar disease. On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration. PMID:26331029

  16. Real Time Pattern Recognition And Feature Analysis From Video Signals Applied To Eye Movement And Pupillary Reflex Monitoring

    NASA Astrophysics Data System (ADS)

    Charlier, Jacques R.; Bariseau, Jean-Luc; Chuffart, Vincent; Marsy, Frangoise; Hache, Jean-Claude

    1984-06-01

    Original techniques for real time pattern recognition and feature analysis from standard video signals have been developed. These techniques have been applied to the monitoring of eye movements and pupillary size during visual field and electrophysio-logical examinations in routine ophtalmological practice. The basic features of the resulting instrument are : 1- the use of low-cost hardware, i.e. standard video equipment and LSI circuitry. 2- the measurement of eye, orientation from the position of the bright pupil relative to the corneal reflection. 3- "real time" processing and high data throughout of 50 samples per second, allowing pupillary and oculomotor reflex analysis. 4- specialized hardware and software permitting an adjustment free feature identifica-tion and analysis directly from video signals. Severe perturbations of the ocular video images can be handled by the system, including partial occlusions of the pupil with eye lids or eye lashes, fluctuations of amplitude levels and parasite light reflections.

  17. Spontaneous dislocation of a crystalline lens to the anterior chamber with pupillary block glaucoma in Noonan Syndrome: a case report

    PubMed Central

    Mukhopadhyaya, Udayaditya; Chakraborti, Chandana; Mondal, Anindita; Pattyanayak, Ujjal; Agarwal, Rajesh Kumar; Tripathi, Partha

    2014-01-01

    We report a 13-year-old child with Noonan Syndrome who developed spontaneous dislocation of the crystalline lens in anterior chamber leading to pupillary block glaucoma in the left eye and subluxation of lens in right eye. Intracapsular extraction of the dislocated lens was done in the left eye. Prompt diagnosis and management is needed in such cases to avoid glaucoma and corneal endothelial cell damage. We could not find any such case after thorough Medline search. PMID:25374640

  18. Time course of post-excitatory effects separates afferent human C fibre classes.

    PubMed

    Weidner, C; Schmidt, R; Schmelz, M; Hilliges, M; Handwerker, H O; Torebjörk, H E

    2000-08-15

    1. To study post-excitatory changes of conduction velocity, action potentials were recorded from 132 unmyelinated nerve fibres (C fibres) in cutaneous fascicles of the peroneal nerve using microneurography in healthy human subjects. The 'marking' technique was used to assess responsiveness to mechanical and heat stimuli or sympathetic reflex provocation. 2. C fibres were classified into three major classes: mechano-responsive afferent (n = 76), mechano-insensitive afferent (n = 48) and sympathetic efferent C fibres (n = 8). 3. During regular stimulation at 0.25 Hz, conditioning pulses were intermittently interposed. Changes of conduction velocity were assessed for different numbers of conditioning impulses and varying interstimulus intervals (ISIs). For all three fibre classes the latency shift following conditioning pulses at an ISI of 1000 ms increased linearly with their number (n = 1, 2 and 4). However, the absolute degree of conduction velocity slowing was much higher in the 32 mechano-insensitive fibres as compared with 56 mechano-responsive or 8 sympathetic fibres. 4. Single additional pulses were interposed at different ISIs from 20 to 2000 ms. For 20 mechano-responsive fibres conduction velocity slowing increased with decreasing ISI (subnormal phase). In contrast, for 16 mechano-insensitive C fibres the conduction velocity slowing decreased with shorter ISIs, and at values lower than 417 +/- 49 ms (mean +/- s.e.m.) the conduction velocity of the conditioned action potential was faster than before (conduction velocity speeding). This supernormal phase had its maximum at 69 +/- 10 ms. 5. In this study we provide, for the first time, direct evidence of relative supernormal conduction in human mechano-insensitive C fibres. The implications for temporal coding in different afferent C fibre classes are discussed. PMID:10944181

  19. Time course of post-excitatory effects separates afferent human C fibre classes

    PubMed Central

    Weidner, C; Schmidt, R; Schmelz, M; Hilliges, M; Handwerker, H O; Torebjörk, H E

    2000-01-01

    To study post-excitatory changes of conduction velocity, action potentials were recorded from 132 unmyelinated nerve fibres (C fibres) in cutaneous fascicles of the peroneal nerve using microneurography in healthy human subjects. The ‘marking’ technique was used to assess responsiveness to mechanical and heat stimuli or sympathetic reflex provocation. C fibres were classified into three major classes: mechano-responsive afferent (n = 76), mechano-insensitive afferent (n = 48) and sympathetic efferent C fibres (n = 8). During regular stimulation at 0.25 Hz, conditioning pulses were intermittently interposed. Changes of conduction velocity were assessed for different numbers of conditioning impulses and varying interstimulus intervals (ISIs). For all three fibre classes the latency shift following conditioning pulses at an ISI of 1000 ms increased linearly with their number (n = 1, 2 and 4). However, the absolute degree of conduction velocity slowing was much higher in the 32 mechano-insensitive fibres as compared with 56 mechano-responsive or 8 sympathetic fibres. Single additional pulses were interposed at different ISIs from 20 to 2000 ms. For 20 mechano-responsive fibres conduction velocity slowing increased with decreasing ISI (subnormal phase). In contrast, for 16 mechano-insensitive C fibres the conduction velocity slowing decreased with shorter ISIs, and at values lower than 417 ± 49 ms (mean ±s.e.m.) the conduction velocity of the conditioned action potential was faster than before (conduction velocity speeding). This supernormal phase had its maximum at 69 ± 10 ms. In this study we provide, for the first time, direct evidence of relative supernormal conduction in human mechano-insensitive C fibres. The implications for temporal coding in different afferent C fibre classes are discussed. PMID:10944181

  20. Directional sound sensitivity in utricular afferents in the toadfish Opsanus tau.

    PubMed

    Maruska, Karen P; Mensinger, Allen F

    2015-06-01

    The inner ear of fishes contains three paired otolithic end organs, the saccule, lagena and utricle, which function as biological accelerometers. The saccule is the largest otolith in most fishes and much of our current understanding on auditory function in this diverse group of vertebrates is derived from anatomical and neurophysiological studies on this end organ. In contrast, less is known about how the utricle contributes to auditory functions. In this study, chronically implanted electrodes were used, along with neural telemetry or tethers to record primary afferent responses from the utricular nerve in free-ranging and naturally behaving oyster toadfish Opsanus tau Linnaeus. The hypothesis was that the utricle plays a role in detecting underwater sounds, including conspecific vocalizations, and exhibits directional sensitivity. Utricular afferents responded best to low frequency (80-200 Hz) pure tones and to playbacks of conspecific boatwhistles and grunts (80-180 Hz fundamental frequency), with the majority of the units (∼75%) displaying a clear, directional response, which may allow the utricle to contribute to sound detection and localization during social interactions. Responses were well within the sound intensity levels of toadfish vocalization (approximately 140 SPL dBrms re. 1 µPa with fibers sensitive to thresholds of approximately 120 SPL dBrms re. 1 µPa). Neurons were also stimulated by self-generated body movements such as opercular movements and swimming. This study is the first to investigate underwater sound-evoked response properties of primary afferents from the utricle of an unrestrained/unanesthetized free-swimming teleost fish. These data provide experimental evidence that the utricle has an auditory function, and can contribute to directional hearing to facilitate sound localization. PMID:25883378

  1. Afferent input-associated reduction of muscle activity in microgravity environment.

    PubMed

    Kawano, F; Nomura, T; Ishihara, A; Nonaka, I; Ohira, Y

    2002-01-01

    Responses of electromyogram (EMG) of soleus, lateral portion of gastrocnemius (LG) and tibialis anterior (TA), and both afferent and efferent neurograms at the L(5) segmental level of the spinal cord, to altered gravity levels created by the parabolic flight of a jet airplane were investigated in adult rats. The EMG activity in antigravity soleus muscle gradually increased when the gravity was elevated from 1-G to 1.5-G (+23%) and 2-G (+67%) during the ascending phase of parabolic flight. The activity decreased approximately 72% from the 1-G level immediately when the rat was exposed to microgravity. The EMG level was maintained low during the 20-s microgravity, but it was restored immediately once the gravity level was increased to 1.5-G and then 1-G during the descending and recovery phase. The EMG level of LG also increased gradually when the gravity level was elevated and the level then decreased when the rat was exposed to microgravity (P>0.05). However, the activity level during the 20-s microgravity was identical to that obtained at 1-G. The EMG level of TA even increased insignificantly in response to the exposure to microgravity. The responses of afferent neurogram were similar to those of soleus EMG, even though the magnitude of the reduction of integrated neurogram level in response to microgravity exposure was small (approximately 26% vs. 1-G level) relative to that of soleus EMG. The level of efferent neurogram was also decreased, but only approximately 9% vs. 1-G level, during the 20-s microgravity. The data in the current study suggest that the afferent input is closely associated with the gravity-dependent muscular activity. PMID:12379265

  2. Dual Modulation of Nociception and Cardiovascular Reflexes during Peripheral Ischemia through P2Y1 Receptor-Dependent Sensitization of Muscle Afferents

    PubMed Central

    Queme, Luis F.; Ross, Jessica L.; Lu, Peilin; Hudgins, Renita C.

    2016-01-01

    Numerous musculoskeletal pain disorders are based in dysfunction of peripheral perfusion and are often comorbid with altered cardiovascular responses to muscle contraction/exercise. We have recently found in mice that 24 h peripheral ischemia induced by a surgical occlusion of the brachial artery (BAO) induces increased paw-guarding behaviors, mechanical hypersensitivity, and decreased grip strength. These behavioral changes corresponded to increased heat sensitivity as well as an increase in the numbers of chemosensitive group III/IV muscle afferents as assessed by an ex vivo forepaw muscles/median and ulnar nerves/dorsal root ganglion (DRG)/spinal cord (SC) recording preparation. Behaviors also corresponded to specific upregulation of the ADP-responsive P2Y1 receptor in the DRGs. Since group III/IV muscle afferents have separately been associated with regulating muscle nociception and exercise pressor reflexes (EPRs), and P2Y1 has been linked to heat responsiveness and phenotypic switching in cutaneous afferents, we sought to determine whether upregulation of P2Y1 was responsible for the observed alterations in muscle afferent function, leading to modulation of muscle pain-related behaviors and EPRs after BAO. Using an afferent-specific siRNA knockdown strategy, we found that inhibition of P2Y1 during BAO not only prevented the increased mean blood pressure after forced exercise, but also significantly reduced alterations in pain-related behaviors. Selective P2Y1 knockdown also prevented the increased firing to heat stimuli and the BAO-induced phenotypic switch in chemosensitive muscle afferents, potentially through regulating membrane expression of acid sensing ion channel 3. These results suggest that enhanced P2Y1 in muscle afferents during ischemic-like conditions may dually regulate muscle nociception and cardiovascular reflexes. SIGNIFICANCE STATEMENT Our current results suggest that P2Y1 modulates heat responsiveness and chemosensation in muscle afferents

  3. Effect of excitatory and inhibitory agents and a glial inhibitor on optically-recorded primary-afferent excitation.

    PubMed

    Ikeda, Hiroshi; Kiritoshi, Takaki; Murase, Kazuyuki

    2008-01-01

    The effects of GABA, excitatory amino-acid receptors antagonists and a glial metabolism inhibitor on primary-afferent excitation in the spinal dorsal horn were studied by imaging the presynaptic excitation of high-threshold afferents in cord slices from young rats with a voltage-sensitive dye. Primary afferent fibers and terminals were anterogradely labeled with a voltage-sensitive dye from the dorsal root attached to the spinal cord slice. Single-pulse stimulation of C fiber-activating strength to the dorsal root elicited compound action potential-like optical responses in the superficial dorsal horn. The evoked presynaptic excitation was increased by the GABAA receptor antagonists picrotoxin and bicuculline, by glutamate receptor antagonists D-AP5 and CNQX, and by the glial metabolism inhibitor mono-fluoroacetic acid (MFA). The increase in presynaptic excitation by picrotoxin was inhibited in the presence of D-AP5, CNQX and MFA. Presynaptic modulation in the central terminal of fine primary afferents by excitatory and inhibitory amino acids may represent a mechanism that regulates the transmission of pain. PMID:18817580

  4. Cryptococcal heat shock protein 70 homolog Ssa1 contributes to pulmonary expansion of Cryptococcus neoformans during the afferent phase of the immune response by promoting macrophage M2 polarization.

    PubMed

    Eastman, Alison J; He, Xiumiao; Qiu, Yafeng; Davis, Michael J; Vedula, Priya; Lyons, Daniel M; Park, Yoon-Dong; Hardison, Sarah E; Malachowski, Antoni N; Osterholzer, John J; Wormley, Floyd L; Williamson, Peter R; Olszewski, Michal A

    2015-06-15

    Numerous virulence factors expressed by Cryptococcus neoformans modulate host defenses by promoting nonprotective Th2-biased adaptive immune responses. Prior studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly contributes to serotype D C. neoformans virulence through the induction of laccase, a Th2-skewing and CNS tropic factor. In the present study, we sought to determine whether Ssa1 modulates host defenses in mice infected with a highly virulent serotype A strain of C. neoformans (H99). To investigate this, we assessed pulmonary fungal growth, CNS dissemination, and survival in mice infected with either H99, an SSA1-deleted H99 strain (Δssa1), and a complement strain with restored SSA1 expression (Δssa1::SSA1). Mice infected with the Δssa1 strain displayed substantial reductions in lung fungal burden during the innate phase (days 3 and 7) of the host response, whereas less pronounced reductions were observed during the adaptive phase (day 14) and mouse survival increased only by 5 d. Surprisingly, laccase activity assays revealed that Δssa1 was not laccase deficient, demonstrating that H99 does not require Ssa1 for laccase expression, which explains the CNS tropism we still observed in the Ssa1-deficient strain. Lastly, our immunophenotyping studies showed that Ssa1 directly promotes early M2 skewing of lung mononuclear phagocytes during the innate phase, but not the adaptive phase, of the immune response. We conclude that Ssa1's virulence mechanism in H99 is distinct and laccase-independent. Ssa1 directly interferes with early macrophage polarization, limiting innate control of C. neoformans, but ultimately has no effect on cryptococcal control by adaptive immunity. PMID:25972480

  5. The Role of the Paratrigeminal Nucleus in Vagal Afferent Evoked Respiratory Reflexes: A Neuroanatomical and Functional Study in Guinea Pigs

    PubMed Central

    Driessen, Alexandria K.; Farrell, Michael J.; Mazzone, Stuart B.; McGovern, Alice E.

    2015-01-01

    The respiratory tree receives sensory innervation from the jugular and nodose vagal sensory ganglia. Neurons of these ganglia are derived from embryologically distinct origins and as such demonstrate differing molecular, neurochemical and physiological phenotypes. Furthermore, whereas nodose afferent neurons project to the nucleus of the solitary tract (nTS), recent neuroanatomical studies in rats suggest that jugular neurons have their central terminations in the paratrigeminal nucleus (Pa5). In the present study we confirm that guinea pigs demonstrate a comparable distinction between the brainstem terminations of nodose and jugular ganglia afferents. Thus, microinjection of fluorescently conjugated cholera toxin B (CT-B) neural tracers into the caudal nTS and Pa5 resulted in highly specific retrograde labeling of neurons in the nodose and jugular ganglia, respectively. Whereas, nodose neurons more often expressed 160 KD neurofilament proteins and the alpha3 subunit of Na+/K+ ATPase, significantly more jugular neurons expressed the neuropeptides substance P (SP) and, especially, Calcitonin Gene-Related Peptide (CGRP). Indeed, terminal fibers in the Pa5 compared to the nTS were characterized by their significantly greater expression of CGRP, further supporting the notion that jugular afferents project to trigeminal-related brainstem regions. Electrical stimulation of the guinea pig larynx following selective surgical denervation of the nodose afferent innervation to the larynx (leaving intact the jugular innervation) resulted in stimulus dependent respiratory slowing and eventual apnea. This jugular ganglia neuron mediated response was unaffected by bilateral microinjections of the GABAA agonist muscimol into the nTS, but was abolished by muscimol injected into the Pa5. Taken together these data confirm that jugular and nodose vagal ganglia afferent neurons innervate distinct central circuits and support the notion that multiple peripheral and central pathways

  6. 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. PMID:22707559

  7. Mechanical sensitivity of muscle afferents in a nerve treated with colchicine.

    PubMed

    Proske, U; Luff, A R

    1998-04-01

    The experiments reported here demonstrate that the mechanical sensitivity of peripheral nerve fibres typically seen after injury can be induced without overtly injuring the nerve, but by simply applying colchicine topically to the nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius nerve was exposed and 10 mM colchicine applied topically for 15 min. The animals recovered from the operation normally and showed no subsequent motor deficit. Six days later animals were re-anaesthetised, a laminectomy carried out and responses recorded in single afferents at the level of the dorsal root. It was found that many afferents, particularly those with conduction velocities in the group II-III range, had become sensitive to local mechanical stimulation of the nerve in the region treated with colchicine and showed slowly adapting responses to stretch of the nerve. Many of the smaller fibres exhibited spontaneous activity. Mechanically sensitive afferents exhibited impulse conduction blocks at the colchicine-treated site. Some afferents, which appeared to conduct impulses normally through the treated region, were associated with muscle receptors having normal response properties. However, other muscle receptors were clearly abnormal and were insensitive to muscle stretch or contraction or exhibited only phasic responses. When the nerve was cut proximal to the colchicine-treated site, some, but not all, spontaneous activity was abolished. It was subsequently shown using a collision technique that the activity in some axons had its origin in the cell body in the dorsal root ganglion. In one experiment, it was shown that after nerve section proximal to the colchicine-treated region three of five axons switched their activity from a peripheral to a central origin. It is postulated that colchicine disrupts fast axonal transport of mechanically sensitive or voltage-sensitive ion channels, from the cell body to the peripheral terminals of the axons, leading

  8. Superoxide enhances Ca2+ entry through L-type channels in the renal afferent arteriole.

    PubMed

    Vogel, Paul A; Yang, Xi; Moss, Nicholas G; Arendshorst, William J

    2015-08-01

    Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (P<0.001) and doubled the plateau response. These effects were abolished by tempol and nitroblue tetrazolium, but not by catalase, confirming actions of superoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor-mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor-mediated calcium mobilization. PMID:26034201

  9. Methodology to Determinate Pupillary Responses Based in High Speed Videoculography in Clinical Eye Applications

    NASA Astrophysics Data System (ADS)

    Villamar, Luis A.; Sánchez, Anabel S.; Suaste, Ernesto

    2010-12-01

    The aim of this article is to present the application of high speed videoculography as a tool during the development of a methodology to employ in the ocular clinic diagnostic. It shows exist a significant statistically difference between groups in the time to maximum contraction velocity. And it does not exit a significant statistically difference in the latency and the maximum contraction velocity.

  10. Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

    PubMed

    Chimento, T C; Doshay, D G; Ross, M D

    1994-05-01

    and latency, and the effect of activating synapses individually or simultaneously. Process location affects peak latency and voltage recorded at the heminode. A synapse on a calyceal process produced < or = 8% more depolarization and a 23% increase in peak latency compared with a synapse on a process of a neuron branch. For whole primary afferents, depolarization decreased 40% between simulations of the smallest and largest afferents. Simulations in which membrane resistivity and synaptic conductance were varied while afferent geometry was kept constant indicated that use of 5,000 omega cm2 and 1.0 nS produced results that best fit electrophysiological findings. Synaptic inputs activated simultaneously did not sum linearly at the heminode. Total depolarization was approximately 14% less than a simple summation of responses of synapses activated one at a time.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7914916

  11. Covariation of pupillary and auditory cortical activity in rats under isoflurane anesthesia.

    PubMed

    Takahashi, H; Tokushige, H; Shiramatsu, T I; Noda, T; Kanzaki, R

    2015-08-01

    Very slow fluctuations of spontaneous activities significantly influence not only behavioral performance in a conscious state, but also neural activities in an unconscious state. Covariation of pupil and cortical activities may lend important insights into the state-dependent modulation of stimulus encoding, yet this phenomenon has received little attention, especially with regard to non-visual cortices. In the present study, we investigated co-fluctuation of pupil size and neural activity in the auditory cortex of rats under isoflurane anesthesia. Pupil fluctuation consisted of longitudinal irregular shifts, and 1-min cyclic modulations. Both spontaneous and auditory-evoked potentials (AEPs) covaried with the longitudinal fluctuation of pupil size, but not with the 1-min cycle. Pupil size exhibited a positive correlation with spontaneous activity and negative correlation with AEP amplitude, particularly when the pupil size was beyond the normal range. Stimulus-specific adaptation characterized using an oddball paradigm was less dependent on pupil size than AEP. In contrast to the cortical activity, heart rate covaried with pupil size with the 1-min oscillatory component, but not the non-oscillatory component. Furthermore, light exposure induced the pupil reflex through the autonomic system, but did not modify cortical activity, indicating that autonomic activity was not causing the cortical modulation. These results together suggest that cortical activities spontaneously covary with pupillary activity through central cholinergic modulation that triggers sympathetic nerve activation. Such a state-dependent property may be a confounding factor in cortical electrophysiology studies. PMID:25967265

  12. Effects of changing skin mechanics on the differential sensitivity to surface compliance by tactile afferents in the human finger pad.

    PubMed

    Hudson, Kathryn M; Condon, Melia; Ackerley, Rochelle; McGlone, Francis; Olausson, Håkan; Macefield, Vaughan G; Birznieks, Ingvars

    2015-10-01

    It is not known how changes in skin mechanics affect the responses of cutaneous mechanoreceptors in the finger pads to compression forces. We used venous occlusion to change the stiffness of the fingers and investigated whether this influenced the firing of low-threshold mechanoreceptors to surfaces of differing stiffness. Unitary recordings were made from 10 slowly adapting type I (SAI), 10 fast adapting type I (FAI) and 9 slowly adapting type II (SAII) units via tungsten microelectrodes inserted into the median nerve at the wrist. A servo-controlled stimulator applied ramp-and-hold forces (1, 2, and 4 N) at a constant loading and unloading rate (2 N/s) via a flat 2.5-cm-diameter silicone disk over the center of the finger pad. Nine silicone disks (objects), varying in compliance, were used. Venous occlusion, produced by inflating a sphygmomanometer cuff around the upper arm to 40 ± 5 mmHg, was used to induce swelling of the fingers and increase the compliance of the finger pulp. Venous occlusion had no effect on the firing rates of the SAI afferents, nor on the slopes of the relationship between mean firing rate and object compliance at each amplitude, but did significantly reduce the slopes for the FAI afferents. Although the SAII afferents possess a poor capacity to encode changes in object compliance, mean firing rates were significantly lower during venous occlusion. The finding that venous occlusion had no effect on the firing properties of SAI afferents indicates that these afferents preserve their capacity to encode changes in object compliance, despite changes in skin mechanics. PMID:26269550

  13. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

    PubMed Central

    Oliva, Idaira; Wanat, Matthew J.

    2016-01-01

    Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review, we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders. PMID:27014097

  14. Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors involves calcium and potassium channels.

    PubMed

    Page, A J; O'Donnell, T A; Blackshaw, L A

    2006-01-01

    GABA(B) receptors inhibit mechanosensitivity of visceral afferents. This is associated with reduced triggering of events that lead to gastro-esophageal reflux, with important therapeutic consequences. In other neuronal systems, GABA(B) receptor activation may be linked via G-proteins to reduced N-type Ca(2+) channel opening, increased inward rectifier K(+) channel opening, plus effects on a number of intracellular messengers. Here we aimed to determine the role of Ca(2+) and K(+) channels in the inhibition of vagal afferent mechanoreceptor function by the GABA(B) receptor agonist baclofen. The responses of three types of ferret gastro-esophageal vagal afferents (mucosal, tension and tension mucosal receptors) to graded mechanical stimuli were investigated in vitro. The effects of baclofen (200 microM) alone on these responses were quantified, and the effects of baclofen in the presence of the G-protein-coupled inward rectifier potassium channel blocker Rb(+) (4.7 mM) and/or the N-type calcium channel blocker omega-conotoxin GVIA (0.1 microM). Baclofen inhibition of mucosal receptor mechanosensitivity was abolished by both blockers. Its inhibitory effect on tension mucosal receptors was partly reduced by both. The inhibitory effect of baclofen on tension receptors was unaffected. The data indicate that the inhibitory action of GABA(B) receptors is mediated via different pathways in mucosal, tension and tension mucosal receptors via mechanisms involving both N-type Ca(2+) channels and inwardly rectifying K(+) channels and others. PMID:16289839

  15. An afferent explanation for sexual dimorphism in the aortic baroreflex of rat.

    PubMed

    Santa Cruz Chavez, Grace C; Li, Bai-Yan; Glazebrook, Patricia A; Kunze, Diana L; Schild, John H

    2014-09-15

    Sex differences in baroreflex (BRx) function are well documented. Hormones likely contribute to this dimorphism, but many functional aspects remain unresolved. Our lab has been investigating a subset of vagal sensory neurons that constitute nearly 50% of the total population of myelinated aortic baroreceptors (BR) in female rats but less than 2% in male rats. Termed "Ah," this unique phenotype has many of the nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type BR afferents. In this study, we utilize three distinct experimental protocols to determine if Ah-type barosensory afferents underlie, at least in part, the sex-related differences in BRx function. Electron microscopy of the aortic depressor nerve (ADN) revealed that female rats have less myelin (P < 0.03) and a smaller fiber cross-sectional area (P < 0.05) per BR fiber than male rats. Electrical stimulation of the ADN evoked compound action potentials and nerve conduction profiles that were markedly different (P < 0.01, n = 7 females and n = 9 males). Selective activation of ADN myelinated fibers evoked a BRx-mediated depressor response that was 3-7 times greater in female (n = 16) than in male (n = 17) rats. Interestingly, the most striking hemodynamic difference was functionally dependent upon the rate of myelinated barosensory fiber activation. Only 5-10 Hz of stimulation evoked a rapid, 20- to 30-mmHg reduction in arterial pressure of female rats, whereas rates of 50 Hz or higher were required to elicit a comparable depressor response from male rats. Collectively, our experimental results are suggestive of an alternative myelinated baroreceptor afferent pathway in females that may account for, at least in part, the noted sex-related differences in autonomic control of cardiovascular function. PMID:25038145

  16. 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

  17. 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

  18. Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia.

    PubMed

    Silva, Elaine F; Sera, Celisa T N; Mourão, Aline A; Lopes, Paulo R; Moreira, Marina C S; Ferreira-Neto, Marcos L; Colombari, Débora A S; Cravo, Sérgio L D; Pedrino, Gustavo R

    2015-11-01

    Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (-34 ± 10% and -29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (-4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia. PMID:26440715

  19. Deletion of Shank1 has minimal effects on the molecular composition and function of glutamatergic afferent postsynapses in the mouse inner ear.

    PubMed

    Braude, Jeremy P; Vijayakumar, Sarath; Baumgarner, Katherine; Laurine, Rebecca; Jones, Timothy A; Jones, Sherri M; Pyott, Sonja J

    2015-03-01

    Shank proteins (1-3) are considered the master organizers of glutamatergic postsynaptic densities in the central nervous system, and the genetic deletion of either Shank1, 2, or 3 results in altered composition, form, and strength of glutamatergic postsynapses. To investigate the contribution of Shank proteins to glutamatergic afferent synapses of the inner ear and especially cochlea, we used immunofluorescence and quantitative real time PCR to determine the expression of Shank1, 2, and 3 in the cochlea. Because we found evidence for expression of Shank1 but not 2 and 3, we investigated the morphology, composition, and function of afferent postsynaptic densities from defined tonotopic regions in the cochlea of Shank1(-/-) mice. Using immunofluorescence, we identified subtle changes in the morphology and composition (but not number and localization) of cochlear afferent postsynaptic densities at the lower frequency region (8 kHz) in Shank1(-/-) mice compared to Shank1(+/+) littermates. However, we detected no differences in auditory brainstem responses at matching or higher frequencies. We also identified Shank1 in the vestibular afferent postsynaptic densities, but detected no differences in vestibular sensory evoked potentials in Shank1(-/-) mice compared to Shank1(+/+) littermates. This work suggests that Shank proteins play a different role in the development and maintenance of glutamatergic afferent synapses in the inner ear compared to the central nervous system. PMID:25637745

  20. Deletion of Shank1 has minimal effects on the molecular composition and function of glutamatergic afferent postsynapses in the mouse inner ear

    PubMed Central

    Braude, Jeremy P.; Vijayakumar, Sarath; Baumgarner, Katherine; Laurine, Rebecca; Jones, Timothy A.; Jones, Sherri M.; Pyott, Sonja J.

    2015-01-01

    Shank proteins (1–3) are considered the master organizers of glutamatergic postsynaptic densities in the central nervous system, and the genetic deletion of either Shank1, 2, or 3 results in altered composition, form, and strength of glutamatergic postsynapses. To investigate the contribution of Shank proteins to glutamatergic afferent synapses of the inner ear and especially cochlea, we used immunofluorescence and quantitative real time PCR to determine the expression of Shank1, 2, and 3 in the cochlea. Because we found evidence for expression of Shank1 but not 2 and 3, we investigated the morphology, composition, and function of afferent postsynaptic densities from defined tonotopic regions in the cochlea of Shank1−/− mice. Using immunofluorescence, we identified subtle changes in the morphology and composition (but not number and localization) of cochlear afferent postsynaptic densities at the lower frequency region (8 kHz) in Shank1−/− mice compared to Shank1+/+ littermates. However, we detected no differences in auditory brainstem responses at matching or higher frequencies. We also identified Shank1 in the vestibular afferent postsynaptic densities, but detected no differences in vestibular sensory evoked potentials in Shank1−/− mice compared to Shank1+/+ littermates. This work suggests that Shank proteins play a different role in the development and maintenance of glutamatergic afferent synapses in the inner ear compared to the central nervous system. PMID:25637745

  1. Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-Induced Obesity

    PubMed Central

    Stearns, A. T.; Balakrishnan, A.; Radmanesh, A.; Ashley, S. W.; Rhoads, D. B.

    2014-01-01

    Background We previously demonstrated vagal neural pathways, specifically subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium-glucose cotransporter SGLT1, the intestinal transporter responsible for absorption of dietary glucose. We hypothesized targeting this pathway could be a novel therapy for obesity. We therefore tested the impact of disrupting vagal signaling by total vagotomy or selective vagal de-afferentation on weight gain and fat content in diet-induced obese rats. Methods Male Sprague–Dawley rats (n = 5–8) underwent truncal vagotomy, selective vagal de-afferentation with capsaicin, or sham procedure. Animals were maintained for 11 months on a high-caloric Western diet. Abdominal visceral fat content was assessed by magnetic resonance imaging together with weight of fat pads at harvest. Glucose homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene expression was assessed by qPCR and immunoblotting and function by glucose uptake in everted jejunal sleeves. Results At 11-months, vagotomized rats weighed 19% less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams. Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P = 0.039) in visceral abdominal fat, respectively. There were no changes in blood glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged across all cohorts at 11-months postoperatively. Conclusions Truncal vagotomy led to significant reductions in both diet-induced weight gain and visceral abdominal fat deposition. Vagal de-afferentation led to a more modest, but clinically and statistically significant, reduction in visceral abdominal fat. As increased visceral abdominal fat is associated with excess morbidity and mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery. PMID:22138962

  2. Changes in vagal afferent drive alter tracheobronchial coughing in anesthetized cats.

    PubMed

    Simera, Michal; Poliacek, Ivan; Veternik, Marcel; Babalova, Lucia; Kotmanova, Zuzana; Jakus, Jan

    2016-08-01

    Unilateral cooling of the vagus nerve (<5°C, blocking mainly conductivity of myelinated fibers) and unilateral vagotomy were employed to reduce cough afferent drive in order to evaluate the effects of these interventions on the temporal features of the cough reflex. Twenty pentobarbitone anesthetized, spontaneously breathing cats were used. Cough was induced by mechanical stimulation of the tracheobronchial airways. The number of coughs during vagal cooling was significantly decreased (p<0.001). Inspiratory cough efforts were reduced by approximately 30% (p<0.001) and expiratory motor drive by more than 80% (p<0.001). Temporal analysis showed prolonged inspiratory and expiratory phases, the total cycle duration, its active portion, and the interval between maxima of the diaphragm and the abdominal activity during coughing (p<0.001). There was no significant difference in the average effects on the cough reflex between cooling of the left or the right vagus nerve. Compared to control, vagal cooling produced no significant difference in heart rate and mean arterial blood pressure (p>0.05), however, cold block of vagal conduction reduced respiratory rate (p<0.001). Unilateral vagotomy significantly reduced cough number, cough-related diaphragmatic activity, and relative values of maximum expiratory esophageal pressure (all p<0.05). Our results indicate that reduced cough afferent drive (lower responsiveness) markedly attenuates the motor drive to respiratory pump muscles during coughing and alters cough temporal features. Differences in the effects of unilateral vagal cooling and vagotomy on coughing support an inhibitory role of sensory afferents that are relatively unaffected by cooling of the vagus nerve to 5°C on mechanically induced cough. PMID:27184303

  3. Pupillary reflex measurement predicts insufficient analgesia before endotracheal suctioning in critically ill patients

    PubMed Central

    2013-01-01

    Introduction This study aimed to evaluate the pupillary dilatation reflex (PDR) during a tetanic stimulation to predict insufficient analgesia before nociceptive stimulation in the intensive care unit (ICU). Methods In this prospective non-interventional study in a surgical ICU of a university hospital, PDR was assessed during tetanic stimulation (of 10, 20 or 40 mA) immediately before 40 endotracheal suctionings in 34 deeply sedated patients. An insufficient analgesia during endotracheal suction was defined by an increase of ≥1 point on the Behavioral Pain Scale (BPS). Results A total of 27 (68%) patients had insufficient analgesia. PDR with 10 mA, 20 mA and 40 mA stimulation was higher in patients with insufficient analgesia (P <0.01). The threshold values of the pupil diameter variation during a 10, 20 and 40 mA tetanic stimulation to predict insufficient analgesia during an endotracheal suctioning were 1, 5 and 13% respectively. The areas (95% confidence interval) under the receiver operating curve were 0.70 (0.54 to 0.85), 0.78 (0.61 to 0.91) and 0.85 (0.721 to 0.954) with 10, 20 and 40 mA tetanic stimulations respectively. A sensitivity analysis using the Richmond Agitation Sedation Scale (RASS) confirmed the results. The 40 mA stimulation was poorly tolerated. Conclusions In deeply sedated mechanically ventilated patients, a pupil diameter variation ≥5% during a 20 mA tetanic stimulation was highly predictable of insufficient analgesia during endotracheal suction. A 40 mA tetanic stimulation is painful and should not be used. PMID:23883683

  4. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    PubMed

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  5. Effect of pupillary dilation on Haigis formula-calculated intraocular lens power measurement by using optical biometry

    PubMed Central

    Khambhiphant, Bharkbhum; Sasiwilasagorn, Suganlaya; Chatbunchachai, Nattida; Pongpirul, Krit

    2016-01-01

    Purpose The purpose of this study was to evaluate the effect of pupillary dilation on the Haigis formula-calculated intraocular lens (IOL) power and ocular biometry measurements by using IOLMaster®. Methods A prospective study was performed for biometry measurements of 373 eyes of 192 healthy subjects using the IOLMaster at the outpatient department of King Chulalongkorn Memorial Hospital from February 2013 to July 2013. The axial length (AL), anterior chamber depth (ACD), keratometry (K), and IOL power were measured before and after 1% tropicamide eye drop instillation. The Haigis formula was used in the IOL power calculation with the predicted target to emmetropia. Each parameter was compared by a paired t-test prior to and after pupillary dilation. Bland–Altman plots were also used to determine the agreement between each parameter. Results The mean age of the subjects was 53.74±14.41 years (range 18–93 years). No differences in AL (P=0.03), steepest K (P=0.42), and flattest K (P=0.41) were obtained from the IOLMaster after pupillary dilation. However, ACD and IOL power were significantly different postdilation (P<0.01 and P<0.01, respectively). In ACD and IOL power measurements, the concordance rates were 93.03% and 97.05% within 95% limits of agreement (−0.48 to 0.26 mm and −1.09 to 0.88 D, respectively) in the Bland–Altman plots. Conclusion Biometry measurements in the cycloplegic stage should be considered in the IOL formulas that use parameters other than AL and K. PMID:27555746

  6. Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain of Vestibular Prosthetic Stimulation.

    PubMed

    Phillips, Christopher; Shepherd, Sarah J; Nowack, Amy; Nie, Kaibao; Kaneko, Chris R S; Rubinstein, Jay T; Ling, Leo; Phillips, James O

    2016-02-01

    Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs. In lesioned monkeys, shorter duration studies show preserved but with somewhat lower or higher velocity behavioral responses. It has been proposed that such changes are due to central adaptive changes in the electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that these differences are due to changes in the vestibular periphery in response to activation of the vestibular efferent system. In order to investigate the site of adaptive change in response to electrical stimulation, we performed transtympanic gentamicin perfusions to induce rapid changes in vestibular input in monkeys with long-standing stably functioning vestibular neurostimulators, disambiguating the effects of implantation from the effects of ototoxic lesion. Gentamicin injection was effective in producing a large reduction in natural VOR only when it was performed in the non-implanted ear, suggesting that the implanted ear contributed little to the natural rotational response before injection. Injection of the implanted ear produced a reduction in the vECAP responses in that ear, suggesting that the intact hair cells in the non-functional ipsilateral ear were successfully lesioned by gentamicin, reducing the efficacy of stimulation in that ear. Despite this, injection of both ears produced central plastic changes that resulted in a dramatically increased slow phase velocity nystagmus elicited by electrical stimulation. These results suggest that loss of vestibular afferent activity, and a concurrent loss of electrically elicited vestibular input, produces an

  7. 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

  8. 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

  9. Central changes in primary afferent fibers following peripheral nerve lesions.

    PubMed

    Coggeshall, R E; Lekan, H A; Doubell, T P; Allchorne, A; Woolf, C J

    1997-04-01

    Cutting or crushing rat sciatic nerve does not significantly reduce the number of central myelinated sensory axons in the dorsal roots entering the fourth and fifth lumbar segments even over very extended periods of time. Unmyelinated axons were reduced by approximately 50%, but only long after sciatic nerve lesions (four to eight months), and reinnervation of the peripheral target did not rescue these axons. This indicates that a peripheral nerve lesion sets up a slowly developing but major shift towards large afferent fiber domination of primary afferent input into the spinal cord. In addition, since myelinated axons are never lost, this is good evidence that the cells that give rise to these fibers are also not lost. If this is the case, this would indicate that adult primary sensory neurons with myelinated axons do not depend on peripheral target innervation for survival. PMID:9130791

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

    SciTech Connect

    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 medial 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.

  11. Endothelin-1 induced desensitization in primary afferent neurons

    PubMed Central

    Smith, Terika P.; Smith, Sherika N.; Sweitzer, Sarah M.

    2014-01-01

    Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats, and is elevated during vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) patients. Previously, our lab has shown that a priming dose of ET-1 produces sensitization to capsaicin-induce secondary hyperalgesia. The goal of this study was to determine if the sensitization induced by ET-1 priming is occurring at the level of the primary afferent neuron. Calcium imaging in cultured dorsal root ganglion (DRG) neurons was utilized to examine the effects of ET-1 on primary afferent neurons. ET-1 induces [Ca2+]i transients in unprimed cells. ET-1 induced [Ca2+]i transients are attenuated by priming with ET-1. This priming effect occurs whether the priming dose is given 0-4 days prior to the challenge dose. Similarly, ET-1 priming decreases capsaicin-induced [Ca2+]i transients. At the level of the primary afferent neuron, ET-1 priming has a desensitizing effect on challenge exposures to ET-1 and capsaicin. PMID:25220703

  12. 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.

  13. 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

  14. Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling

    PubMed Central

    Wu, Hao; Williams, John; Nathans, Jeremy

    2012-01-01

    The diversity of cutaneous sensory afferents has been studied by many investigators using behavioral, physiologic, molecular, and genetic approaches. Largely missing, thus far, is an analysis of the complete morphologies of individual afferent arbors. Here we present a survey of cutaneous sensory arbor morphologies in hairy skin of the mouse using genetically-directed sparse labeling with a sensory neuron-specific alkaline phosphatase reporter. Quantitative analyses of 719 arbors, among which 77 were fully reconstructed, reveal 10 morphologically distinct types. Among the two types with the largest arbors, one contacts ∼200 hair follicles with circumferential endings and a second is characterized by a densely ramifying arbor with one to several thousand branches and a total axon length between one-half and one meter. These observations constrain models of receptive field size and structure among cutaneous sensory neurons, and they raise intriguing questions regarding the cellular and developmental mechanisms responsible for this morphological diversity. DOI: http://dx.doi.org/10.7554/eLife.00181.001 PMID:23256042

  15. Factors forming the edge of a receptive field: the presence of relatively ineffective afferent terminals.

    PubMed

    Merrill, E G; Wall, P D

    1972-11-01

    A specialized type of spinal cord cell has its cell body in lamina IV and has a small low threshold cutaneous receptive field which is remarkable for its abrupt edge. No signs could be found of a subliminal fringe to this field since its size remains fixed during wide excursions of the cell's excitability. Reversible blocking of peripheral nerves and dorsal roots showed that the afferents responsible for exciting these cells following natural stimuli, run in a restricted area of peripheral nerve and dorsal root. When the fibres necessary to sustain the natural stimulus receptive field were blocked, it was shown that other large myelinated fibres in neighbouring roots were still capable of firing the cell monosynaptically following electrical stimulation of the root or periphery although no natural stimuli were able to change the cell's excitability. It is necessary to divide the afferent synapses on such cells into a class which is highly effective in firing the cell on natural stimulation and a second class which has no effect yet detected following natural stimuli but which can fire the cell monosynaptically if synchronously activated by electrical stimulation. Suggestions are made for possible presynaptic and post-synaptic mechanisms which might divide the effect of arriving impulses into two such classes. PMID:4637631

  16. Circuit formation and function in the olfactory bulb of mice with reduced spontaneous afferent activity.

    PubMed

    Lorenzon, Paolo; Redolfi, Nelly; Podolsky, Michael J; Zamparo, Ilaria; Franchi, Sira Angela; Pietra, Gianluca; Boccaccio, Anna; Menini, Anna; Murthy, Venkatesh N; Lodovichi, Claudia

    2015-01-01

    The type of neuronal activity required for circuit development is a matter of significant debate. We addressed this issue by analyzing the topographic organization of the olfactory bulb in transgenic mice engineered to have very little afferent spontaneous activity due to the overexpression of the inwardly rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1 mice). In these conditions, the topography of the olfactory bulb was unrefined. Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous afferent activity, although the functional maps were coarser than in controls and contributed to altered olfactory discrimination behavior. In addition, overexpression of Kir2.1 in adults induced a regression of the already refined connectivity to an immature (i.e., coarser) status. Our data suggest that spontaneous activity plays a critical role not only in the development but also in the maintenance of the topography of the olfactory bulb and in sensory information processing. PMID:25568110

  17. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy.

    PubMed

    Haroutounian, Simon; Nikolajsen, Lone; Bendtsen, Thomas F; Finnerup, Nanna B; Kristensen, Anders D; Hasselstrøm, Jørgen B; Jensen, Troels S

    2014-07-01

    Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn, implying a potential autonomous pain-generating mechanism. This study used peripheral nerve blockade and systemic lidocaine administration, with detailed somatosensory assessment, to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain. Fourteen patients with neuropathic pain (7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy) underwent comprehensive characterization of somatosensory function by quantitative sensory testing. Patients were then administered an ultrasound-guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in randomized order. The effect of these interventions on spontaneous pain intensity and on evoked cold, warm, pinprick, and brush responses was assessed at each session. All patients had sensory disturbances at baseline. The peripheral nerve block resulted in a complete abolition of ipsilateral pain within 10 min (median) in all patients, with lidocaine plasma concentrations being too low to account for a systemic effect of the drug. Intravenous lidocaine infusion reduced the spontaneous pain by 45.5% (±31.7%), and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs. However, the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity. This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization, primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy. PMID:24704366

  18. Effect of hypergravity on the development of vestibulocerebellar afferent fibers

    NASA Astrophysics Data System (ADS)

    Bruce, L. L.

    Gravity is a critical factor in the normal development of the vestibular system, as prolonged prenatal exposures to either micro- or hypergravity will alter the pattern of projections from specific vestibular organs to specific targets in the vestibular nuclei. This study addresses the effect of gravity on the development of vestibulocerebellar projections. In adult rats the semicircular canal afferents project mainly to the cerebellar nodulus whereas the otolith maculae project mainly to the ventral uvula of the cerebellum. To determine if the distribution pattern of these afferents is altered by exposures to altered gravity, 10 pregnant rats were exposed to hypergravity (1.5g) from embryonic day 12 (before vestibular ganglion neurons contact vestibular nuclei) to embryonic day 21 (near the time when the vestibular system becomes functional). Controls were exposed to Earth's gravity but otherwise received the same treatment. At the end of the exposure the embryos were deeply anesthetized and fixed by transcardiac perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer (pH7.4). Filter strips coated with DiI and PTIR were implanted into the saccule (gravistatic vestibular receptor) or into the posterior vertical canal (angular acceleration receptor), and allowed to diffuse for 2 weeks at 37°C. Then the brains were dissected and sectioned for fluorescent confocal imaging. Examination of the control cerebella revealed that the canal and otolith afferents have reached the nodulus and uvula, and axons extend into the internal granular, Purkinje, and molecular layers. Projections from the saccule and posterior vertical canal were partially segregated into their respective domains, the uvula and nodulus. In contrast, in hypergravity-exposed rat fetuses the saccule and posterior vertical canal projections were poorly segregated, and both organs contributed labeled fibers to all layers of the nodulus and uvula. This contrasts with the increased afferent segregation

  19. 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.

  20. Breadth of tuning in taste afferent neurons varies with stimulus strength.

    PubMed

    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

  1. A binocular pupil model for simulation of relative afferent pupil defects and the swinging flashlight test.

    PubMed

    Privitera, Claudio M; Stark, Lawrence W

    2006-03-01

    Many important intracranial neural pathways are involved in the control of the two muscles of the human pupil and the observation and analysis of pupil responses to light or other stimuli is of great interest in many clinical procedures. The binocular pupil model presented in this document has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It is employed here to simulate responses to the swinging flashlight test, a procedure which is routinely practiced in ophthalmology to diagnose different degrees of relative afferent pupil defects often a consequence of severe optic nerve diseases or retinal dysfunctions. Other, not light-dependent, pupil stimuli are briefly discussed. PMID:16404612

  2. Micromotional studies of utricular and canal afferents

    NASA Technical Reports Server (NTRS)

    Lewis, Edwin R.

    1989-01-01

    The long-range goal of this research was to refine our understanding of the sensitivity of the vestibular components of the ear to very-low-amplitude motion, especially, the role of gravity in this sensitivity. We focused on the American bullfrog--a common animal subject for vestibular sensory research. Our principal experimental method was to apply precise, sinusoidal microrotational stimuli to an anesthetized animal subject, to record the resulting responses in an individual vestibular nerve fiber from the intact ear, and to use intracellular dye to trace the fiber and thus identify the vestibular sensor that gave rise to it. In this way, we were able to identify specific micromotional sensitivities and to associate those sensitivities definitely with specific sensors. Furthermore, by recording from nerve fibers after they leave the intact inner-ear cavity, we were able to achieve these identifications without interrupting the delicate micromechanics of the inner ear. We were especially concerned with the relative roles of the utricle and the anterior semicircular canal in the sensing of microrotational motion of the head about horizontal axes, and with the role of gravity in mediating that sensing process in the utricle. The functional characterization of individual nerve fibers was accomplished with a conventional analytical tool, the cycle histogram, in which the nerve impulse rate was plotted against the phase of the sinusoidal stimulus.

  3. Mimicking the End Organ Architecture of Slowly Adapting Type I Afferents May Increase the Durability of Artificial Touch Sensors

    PubMed Central

    Lesniak, Daine R.; Gerling, Gregory J.

    2015-01-01

    In effort to mimic the sensitivity and efficient information transfer of natural tactile afferents, recent work has combined force transducers and computational models of mechanosensitive afferents. Sensor durability, another feature important to sensor design, might similarly capitalize upon biological rules. In particular, gains in sensor durability might leverage insight from the compound end organ of the slowly adapting type I afferent, especially its multiple sites of spike initiation that reset each other. This work develops models of compound spiking sensors using a computational network of transduction functions and leaky integrate and fire models (together a spike encoder, the software element of a compound spiking sensor), informed by the output of an existing force transducer (hardware sensing elements of a compound spiking sensor). Individual force transducer failures are simulated with and without resetting between spike encoders to test the importance of both resetting and configuration on system durability. The results indicate that the resetting of adjacent spike encoders, upon the firing of a spike by any one, is an essential mechanism to maintain a stable overall response in the midst of transducer failure. Furthermore, results suggest that when resetting is enabled, the durability of a compound sensor is maximized when individual transducers are paired with spike encoders and multiple, paired units are employed. To explore these ideas more fully, use cases examine the design of a compound sensor to either reach a target lifetime with a set probability or determine how often to schedule maintenance to control the probability of failure. PMID:25705703

  4. Activation of CB1 inhibits NGF-induced sensitization of TRPV1 in adult mouse afferent neurons

    PubMed Central

    Wang, Zun-Yi; McDowell, Thomas; Wang, Peiqing; Alvarez, Roxanne; Gomez, Timothy; Bjorling, Dale E.

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1)-containing afferent neurons convey nociceptive signals and play an essential role in pain sensation. Exposure to nerve growth factor (NGF) rapidly increases TRPV1 activity (sensitization). In the present study, we investigated whether treatment with the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced sensitization of TRPV1 in adult mouse dorsal root ganglion (DRG) afferent neurons. We found that CB1, NGF receptor tyrosine kinase A (trkA), and TRPV1 are present in cultured adult mouse small- to medium-sized afferent neurons and treatment with NGF (100 ng/ml) for 30 minutes significantly increased the number of neurons that responded to capsaicin (as indicated by increased intracellular Ca2+ concentration). Pretreatment with the CB1 agonist ACEA (10 nM) inhibited the NGF-induced response, and this effect of ACEA was reversed by a selective CB1 antagonist. Further, pretreatment with ACEA inhibited NGF-induced phosphorylation of AKT. Blocking PI3 kinase activity also attenuated the NGF-induced increase in the number of neurons that responded to capsaicin. Our results indicate that the analgesic effect of CB1 activation may in part be due to inhibition of NGF-induced sensitization of TRPV1 and also that the effect of CB1 activation is at least partly mediated by attenuation of NGF-induced increased PI3 signaling. PMID:25088915

  5. Spinal inhibition of phrenic motoneurones by stimulation of afferents from leg muscle in the cat: blockade by strychnine.

    PubMed

    Eldridge, F L; Millhorn, D E; Waldrop, T

    1987-08-01

    1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in paralysed high (C1) spinal cats whose phrenic nerve activity was evoked by activation of the intercostal-to-phrenic reflex. End-tidal PCO2 was maintained at a constant level by means of a servo-controlled ventilator. 2. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve uniformly caused inhibition of phrenic activity evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued, and there was a post-stimulus augmentation of phrenic activity. 3. Pre-treatment with subconvulsive doses of strychnine, an antagonist of the neurotransmitter glycine, partially or completely blocked the inhibitory effects on phrenic activity of muscle-afferent stimulation. The blockade was reversible with time. 4. Pre-treatment with a subconvulsive dose of bicuculline, an antagonist of the neurotransmitter gamma-aminobutyric acid (GABA), had no effect on the inhibitory mechanism. 5. We conclude that glycine is an important transmitter of the inhibition of phrenic motoneurones induced by muscle-afferent stimulation, but that GABA is not involved in this inhibitory mechanism. PMID:3681723

  6. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus.

    PubMed

    Yu, Xiaoyun; Hu, Youtian; Yu, Shaoyong

    2014-08-15

    Acid reflux-induced heartburn and noncardiac chest pain are processed peripherally by sensory nerve endings in the wall of the esophagus, but the underlying mechanism is still unclear. This study aims to determine the effects of acid on esophageal vagal nociceptive afferent subtypes. Extracellular single-unit recordings were performed in guinea pig vagal nodose or jugular C fiber neurons by using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. We recorded action potentials (AP) of esophageal nodose or jugular C fibers evoked by acid perfusion and compared esophageal distension-evoked AP before and after acid perfusion. Acid perfusion for 30 min (pH range 7.4 to 5.8) did not evoke AP in nodose C fibers but significantly decreased their responses to esophageal distension, which could be recovered after washing out acid for 90 min. In jugular C fibers, acid perfusion not only evoked AP but also inhibited their responses to esophageal distension, which were not recovered after washing out acid for 120 min. Lower concentration of capsaicin perfusion mimicked acid-induced effects in nodose and jugular C fibers. Pretreatment with TRPV1 antagonist AMG9810, but not acid-sensing ion channel (ASIC) inhibitor amiloride, significantly inhibited acid-induced effects in nodose and jugular C fiber. These results demonstrate that esophageal vagal nociceptive afferent nerve subtypes display distinctive responses to acid. Acid activates jugular, but not nodose, C fibers and inhibits both of their responses to esophageal distension. These effects are mediated mainly through TRPV1. This inhibitory effect is a novel finding and may contribute to esophageal sensory/motor dysfunction in acid reflux diseases. PMID:24994852

  7. Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents.

    PubMed

    Hofmann, Mackenzie E; Andresen, Michael C

    2016-02-01

    Vanilloids, high temperature, and low pH activate the transient receptor potential vanilloid type 1 (TRPV1) receptor. In spinal dorsal root ganglia, co-activation of one of these gating sites on TRPV1 sensitized receptor gating by other modes. Here in rat brainstem slices, we examined glutamate synaptic transmission in nucleus of the solitary tract (NTS) neurons where most cranial primary afferents express TRPV1, but TRPV1 sensitization is unknown. Electrical shocks to the solitary tract (ST) evoked EPSCs (ST-EPSCs). Activation of TRPV1 with capsaicin (100 nM) increased spontaneous EPSCs (sEPSCs) but inhibited ST-EPSCs. High concentrations of the ultra-potent vanilloid resiniferatoxin (RTX, 1 nM) similarly increased sEPSC rates but blocked ST-EPSCs. Lowering the RTX concentration to 150 pM modestly increased the frequency of the sEPSCs without causing failures in the evoked ST-EPSCs. The sEPSC rate increased with raising bath temperature to 36 °C. Such thermal responses were larger in 150 pM RTX, while the ST-EPSCs remained unaffected. Vanilloid sensitization of thermal responses persisted in TTX but was blocked by the TRPV1 antagonist capsazepine. Our results demonstrate that multimodal activation of TRPV1 facilitates sEPSC responses in more than the arithmetic sum of the two activators, i.e. co-activation sensitizes TRPV1 control of spontaneous glutamate release. Since action potential evoked glutamate release is unaltered, the work provides evidence for cooperativity in gating TRPV1 plus a remarkable separation of calcium mechanisms governing the independent vesicle pools responsible for spontaneous and evoked release at primary afferents in the NTS. PMID:26471418

  8. 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. PMID:22323647

  9. GABAergic Afferents activate both GABAA and GABAB receptors in mouse substantia nigra dopaminergic neurons in vivo

    PubMed Central

    Brazhnik, Elena; Shah, Fulva; Tepper, James M.

    2008-01-01

    Most in vivo electrophysiological studies of substantia nigra have employed rats. With the recent proliferation of the use of mice for in vitro neurophysiological studies due to the availability of various genetically modified strains to identify the roles of various channels and proteins in neuronal function, it is crucial to obtain data on in vivo responses in mice to verify that the in vitro results reflect functioning of systems comparable to those that have been well studied in rat. Inhibitory responses of rat nigral dopaminergic neurons by stimulation of afferents from striatum, globus pallidus or pars reticulata have been shown to be mediated predominantly or exclusively by GABAA receptors. This is puzzling given the substantial expression of GABAB receptors and the ubiquitous appearance of GABAB synaptic responses in rat dopaminergic neurons in vitro. In the present study we studied electrically evoked GABAergic inhibition in nigral dopaminergic neurons in C57BL/6J mice. Stimulation of the three major GABAergic inputs elicited stronger and longer lasting inhibitory responses than those seen in rats. The early inhibition was GABAA mediated, whereas the later component, absent in rats, was GABAB mediated and selectively enhanced by GABA uptake inhibition. Striatal-evoked inhibition exhibited a slower onset and a weaker initial component compared to inhibition from globus pallidus or substantia nigra pars reticulata. These results are discussed with respect to differences in the size and neuronal density of the rat and mouse brain, and the different sites of synaptic contact of the synapses from the three GABAergic afferents. PMID:18842898

  10. Afferents of the lamprey optic tectum with special reference to the GABA input: combined tracing and immunohistochemical study.

    PubMed

    Robertson, Brita; Saitoh, Kazuya; Ménard, Ariane; Grillner, Sten

    2006-11-01

    The optic tectum in the lamprey midbrain, homologue of the superior colliculus in mammals, is important for eye movement control and orienting responses. There is, however, only limited information regarding the afferent input to the optic tectum except for that from the eyes. The objective of this study was to define specifically the gamma-aminobutyric acid (GABA)-ergic projections to the optic tectum in the river lamprey (Lampetra fluviatilis) and also to describe the tectal afferent input in general. The origin of afferents to the optic tectum was studied by using the neuronal tracer neurobiotin. Injection of neurobiotin into the optic tectum resulted in retrograde labelling of cell groups in all major subdivisions of the brain. The main areas shown to project to the optic tectum were the following: the caudoventral part of the medial pallium, the area of the ventral thalamus and dorsal thalamus, the nucleus of the posterior commissure, the torus semicircularis, the mesencephalic M5 nucleus of Schober, the mesencephalic reticular area, the ishtmic area, and the octavolateral nuclei. GABAergic projections to the optic tectum were identified by combining neurobiotin tracing and GABA immunohistochemistry. On the basis of these double-labelling experiments, it was shown that the optic tectum receives a GABAergic input from the caudoventral part of the medial pallium, the dorsal and ventral thalamus, the nucleus of M5, and the torus semicircularis. The afferent input to the optic tectum in the lamprey brain is similar to that described for other vertebrate species, which is of particular interest considering its position in phylogeny. PMID:16958107

  11. Cardiac modulation of startle is altered in depersonalization-/derealization disorder: Evidence for impaired brainstem representation of baro-afferent neural traffic.

    PubMed

    Schulz, André; Matthey, Jan Hendrik; Vögele, Claus; Schaan, Violetta; Schächinger, Hartmut; Adler, Julia; Beutel, Manfred E; Michal, Matthias

    2016-06-30

    Patients with depersonalization-/derealization disorder (DPD) show altered heartbeat-evoked brain potentials, which are considered psychophysiological indicators of cortical representation of visceral-afferent neural signals. The aim of the current investigation was to clarify whether the impaired CNS representation of visceral-afferent neural signals in DPD is restricted to the cortical level or is also present in sub-cortical structures. We used cardiac modulation of startle (CMS) to assess baro-afferent signal transmission at brainstem level in 22 DPD and 23 healthy control individuals. The CMS paradigm involved acoustic startle stimuli (105dB(A), 50ms) elicited 0, 100, 200, 300, 400 and 500ms after a cardiac R-wave. In healthy control individuals, we observed lower startle responses at 100 and 300ms than at 0 and 400ms after an R-wave. In DPD patients, no effect of the cardiac cycle on startle response magnitude was found. We conclude that the representation of visceral-afferent neural signals at brainstem level may be deficient in DPD. This effect may be due to increased peripheral sympathetic tone or to dysregulated signal processing at brainstem level. PMID:27078753

  12. Corneal afferents differentially target thalamic- and parabrachial-projecting neurons in trigeminal subnucleus caudalis

    PubMed Central

    Aicher, Sue A.; Hermes, Sam M.; Hegarty, Deborah M.

    2012-01-01

    Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal subnucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. PMID:23201828

  13. Predicted effects of nitric oxide and superoxide on the vasoactivity of the afferent arteriole.

    PubMed

    Layton, Anita T; Edwards, Aurélie

    2015-10-15

    We expanded a published mathematical model of an afferent arteriole smooth muscle cell in rat kidney (Edwards A, Layton, AT. Am J Physiol Renal Physiol 306: F34-F48, 2014) to understand how nitric oxide (NO) and superoxide (O(2)(-)) modulate the arteriolar diameter and its myogenic response. The present model includes the kinetics of NO and O(2)(-) formation, diffusion, and reaction. Also included are the effects of NO and its second messenger cGMP on cellular Ca²⁺ uptake and efflux, Ca²⁺-activated K⁺ currents, and myosin light chain phosphatase activity. The model considers as well pressure-induced increases in O(2)(-) production, O(2)(-)-mediated regulation of L-type Ca²⁺ channel conductance, and increased O(2)(-) production in spontaneous hypertensive rats (SHR). Our results indicate that elevated O(2)(-) production in SHR is sufficient to account for observed differences between normotensive and hypertensive rats in the response of the afferent arteriole to NO synthase inhibition, Tempol, and angiotensin II at baseline perfusion pressures. In vitro, whether the myogenic response is stronger in SHR remains uncertain. Our model predicts that if mechanosensitive cation channels are not modulated by O(2)(-), then fractional changes in diameter induced by pressure elevations should be smaller in SHR than in normotensive rats. Our results also suggest that most NO diffuses out of the smooth muscle cell without being consumed, whereas most O(2)(-) is scavenged, by NO and superoxide dismutase. Moreover, the predicted effects of superoxide on arteriolar constriction are not predominantly due to its scavenging of NO. PMID:26180238

  14. Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans.

    PubMed

    Smith, Scott A; Querry, Ross G; Fadel, Paul J; Gallagher, Kevin M; Strømstad, Morten; Ide, Kojiro; Raven, Peter B; Secher, Niels H

    2003-09-15

    During exercise, the carotid baroreflex is reset to operate around the higher arterial pressures evoked by physical exertion. The purpose of this investigation was to evaluate the contribution of somatosensory input from the exercise pressor reflex to this resetting during exercise. Nine subjects performed seven minutes of dynamic cycling at 30% of maximal work load and three minutes of static one-legged contraction at 25% maximal voluntary contraction before (control) and after partial blockade of skeletal muscle afferents with epidural anaesthesia. Carotid baroreflex function was assessed by applying rapid pulses of hyper- and hypotensive stimuli to the neck via a customised collar. Using a logistic model, heart rate (HR) and mean arterial pressure (MAP) responses to carotid sinus stimulation were used to develop reflex function stimulus-response curves. Compared with rest, control dynamic and static exercise reset carotid baroreflex-HR and carotid baroreflex-MAP curves vertically upward on the response arm and laterally rightward to higher operating pressures. Inhibition of exercise pressor reflex input by epidural anaesthesia attenuated the bi-directional resetting of the carotid baroreflex-MAP curve during both exercise protocols. In contrast, the effect of epidural anaesthesia on the resetting of the carotid baroreflex-HR curve was negligible during dynamic cycling whereas it relocated the curve in a laterally leftward direction during static contraction. The data suggest that afferent input from skeletal muscle is requisite for the complete resetting of the carotid baroreflex during exercise. However, this neural input appears to modify baroreflex control of blood pressure to a greater extent than heart rate. PMID:12819303

  15. Mechano- and thermosensitivity of regenerating cutaneous afferent nerve fibers.

    PubMed

    Jänig, Wilfrid; Grossmann, Lydia; Gorodetskaya, Natalia

    2009-06-01

    Crush lesion of a skin nerve is followed by sprouting of myelinated (A) and unmyelinated (C) afferent fibers into the distal nerve stump. Here, we investigate quantitatively both ongoing activity and activity evoked by mechanical or thermal stimulation of the nerve in 43 A- and 135 C-fibers after crush lesion of the sural nerve using neurophysiological recordings in anesthetized rats. The discharge patterns in the injured afferent nerve fibers and in intact (control) afferent nerve fibers were compared. (1) Almost all (98%) A-fibers were mechanosensitive, some of them exhibited additionally weak cold/heat sensitivity; 7% had ongoing activity. (2) Three patterns of physiologically evoked activity were present in the lesioned C-fibers: (a) C-fibers with type 1 cold sensitivity (low cold threshold, inhibition on heating, high level of ongoing and cold-evoked activity; 23%): almost all of them were mechanoinsensitive and 40% of them were additionally heat-sensitive; (b) C-fibers with type 2 cold sensitivity (high cold threshold, low level of ongoing and cold-evoked activity; 23%). All of them were excited by mechanical and/or heat stimuli; (c) cold-insensitive C-fibers (54%), which were heat- and/or mechanosensitive. (3) The proportions of C-fibers exhibiting these three patterns of discharge to physiological stimuli were almost identical in the population of injured C-fibers and in a population of 91 intact cutaneous C-fibers. 4. Ongoing activity was present in 56% of the lesioned C-fibers. Incidence and rate of ongoing activity were the same in the populations of lesioned and intact type 1 cold-sensitive C-fibers. The incidence (but not rate) of ongoing activity was significantly higher in lesioned type 2 cold-sensitive and cold insensitive C-fibers than in the corresponding populations of intact C-fibers (42/93 fibers vs. 11/72 fibers). PMID:19139872

  16. 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

  17. Models of ensemble firing of muscle spindle afferents recorded during normal locomotion in cats

    PubMed Central

    Prochazka, Arthur; Gorassini, Monica

    1998-01-01

    The aim of this work was to compare the ability of several mathematical models to predict the firing characteristics of muscle spindle primary afferents recorded chronically during normal stepping in cats. Ensemble firing profiles of nine hamstring spindle primary (presumed group Ia) afferents were compiled from stored data from 132 step cycles. Three sets of profiles corresponding to slow, medium and fast steps were generated by averaging groups of step cycles aligned to peak muscle length in each cycle. Five models obtained from the literature were compared. Each of these models was used to predict the spindle firing profiles from the averaged muscle length signals. The models were also used in the reverse direction, namely to predict muscle length from the firing profiles. A sixth model incorporating some key aspects of the other models was also included in the comparisons. Five of the models predicted spindle firing well, with root mean square (r.m.s.) errors lower than 14% of the modulation depth of the target profiles. The key variable in achieving good predictions was muscle velocity, the best fits being obtained with power-law functions of velocity, with an exponent of 0.5 or 0.6 (i.e. spindle firing rate is approximately proportional to the square root of muscle velocity). The fits were slightly improved by adding small components of EMG signal to mimic fusimotor action linked to muscle activation. The modest relative size of EMG-linked fusimotor action may be related to the fact that hamstring muscles are not strongly recruited in stepping. Length was predicted very accurately from firing profiles with the inverse of the above models, indicating that the nervous system could in principle process spindle firing in a relatively simple way to give accurate information on muscle length. The responses of the models to standard ramp-and-hold displacements at 10 mm s−1 were also studied (i.e. velocities that were an order of magnitude lower than that during

  18. Bladder afferent hyperexcitability in bladder pain syndrome/interstitial cystitis

    PubMed Central

    Yoshimura, Naoki; Oguchi, Tomohiko; Yokoyama, Hitoshi; Funahashi, Yasuhito; Yoshikawa, Satoru; Sugino, Yoshio; Kawamorita, Naoki; Kashyap, Mahendra P; Chancellor, Michael B; Tyagi, Pradeep; Ogawa, Teruyuki

    2014-01-01

    Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development. Further investigation of the pathophysiology will lead to the effective treatment of patients with bladder pain syndrome/interstitial cystitis. PMID:24807488

  19. 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. PMID:26581873

  20. Direct targeting of peptidergic amygdalar neurons by noradrenergic afferents: linking stress-integrative circuitry

    PubMed Central

    Kravets, J. L.; Reyes, B. A. S.; Unterwald, E. M.; Van Bockstaele, E. J.

    2014-01-01

    Amygdalar norepinephrine (NE) plays a key role in regulating neural responses to emotionally arousing stimuli and is involved in memory consolidation of emotionally charged events. Corticotropin-releasing factor (CRF) and dynorphin (DYN), two neuropeptides that mediate the physiological and behavioral responses to stress, are abundant in the central nucleus of the amygdala (CeA), and directly innervate brainstem noradrenergic locus coeruleus (LC) neurons. Whether the CRF- and DYN-containing amygdalar neurons receive direct noradrenergic innervation has not yet been elucidated. The present study sought to define cellular substrates underlying noradrenergic modulation of CRF- and DYN-containing neurons in the CeA using immunohistochemistry and electron microscopy. Ultrastructural analysis revealed that NE-labeled axon terminals form synapses with CRF- and DYN-containing neurons in the CeA. Semi-quantitative analysis showed that approximately 31% of NET-labeled axon terminals targeted CeA neurons that co-expressed DYN and CRF. As a major source of CRF innervation to the LC, it is also not known whether CRF-containing CeA neurons are directly targeted by noradrenergic afferents. To test this, retrograde tract-tracing using FluoroGold (FG) from the LC was combined with immunocytochemical detection of CRF and NET in the CeA. Our results revealed a population of LC-projecting CRF-containing CeA neurons that are directly innervated by NE afferents. Analysis showed that approximately 34% of NET-labeled axon terminals targeted LC-projecting CeA neurons that contain CRF. Taken together, these results indicate significant interactions between NE, CRF, and DYN in this critical limbic region and reveal direct synaptic interactions of NE with amygdalar CRF that influence the LC-NE arousal system. PMID:24271021

  1. 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.

  2. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents

    PubMed Central

    Gutierrez, Silvia; Aschenbrenner, Carol A.; Houle, Timothy T.; Hayashida, Ken-ichiro; Ririe, Douglas G.; Eisenach, James C.

    2014-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical

  3. Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity.

    PubMed

    Allen, A M

    1998-08-01

    1. A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1, Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype. 2. The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells. 3. To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95 % O2, 5 % CO2), maintained at 36 C, and multi-unit nerve activity recorded with a suction electrode. 4. Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 +/- 11 % with 10 nM angiotensin II) with a threshold concentration of 1 nM. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 microM), but not by the addition of an AT2 receptor antagonist, PD123319 (1 microM). 5. In approximately 50 % of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 +/- 8 % with 10 nM angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319. 6. These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function. PMID:9660892

  4. Trafficking of Na+/Ca2+ exchanger to the site of persistent inflammation in nociceptive afferents.

    PubMed

    Scheff, Nicole N; Gold, Michael S

    2015-06-01

    Persistent inflammation results in an increase in the amplitude and duration of depolarization-evoked Ca(2+) transients in putative nociceptive afferents. Previous data indicated that these changes were the result of neither increased neuronal excitability nor an increase in the amplitude of depolarization. Subsequent data also ruled out an increase in voltage-gated Ca(2+) currents and recruitment of Ca(2+)-induced Ca(2+) release. Parametric studies indicated that the inflammation-induced increase in the duration of the evoked Ca(2+) transient required a relatively large and long-lasting increase in the concentration of intracellular Ca(2+) implicating the Na(+)/Ca(2+) exchanger (NCX), a major Ca(2+) extrusion mechanism activated with high intracellular Ca(2+) loads. The contribution of NCX to the inflammation-induced increase in the evoked Ca(2+) transient in rat sensory neurons was tested using fura-2 AM imaging and electrophysiological recordings. Changes in NCX expression and protein were assessed with real-time PCR and Western blot analysis, respectively. An inflammation-induced decrease in NCX activity was observed in a subpopulation of putative nociceptive neurons innervating the site of inflammation. The time course of the decrease in NCX activity paralleled that of the inflammation-induced changes in nociceptive behavior. The change in NCX3 in the cell body was associated with a decrease in NCX3 protein in the ganglia, an increase in the peripheral nerve (sciatic) yet no change in the central root. This single response to inflammation is associated with changes in at least three different segments of the primary afferent, all of which are likely to contribute to the dynamic response to persistent inflammation. PMID:26041911

  5. Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity

    PubMed Central

    Allen, A M

    1998-01-01

    A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1,Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype.The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells.To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95% O2, 5% CO2), maintained at 36 °C, and multi-unit nerve activity recorded with a suction electrode.Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 ± 11% with 10 nm angiotensin II) with a threshold concentration of 1 nm. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 μm), but not by the addition of an AT2 receptor antagonist, PD123319 (1 μm).In approximately 50% of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 ± 8% with 10 nm angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319.These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function. PMID:9660892

  6. Cortical Processing of Respiratory Afferent Stimuli during Sleep in Children with the Obstructive Sleep Apnea Syndrome

    PubMed Central

    Huang, Jingtao; Colrain, Ian M.; Melendres, M. Cecilia; Karamessinis, Laurie R.; Pepe, Michelle E.; Samuel, John M.; Abi-Raad, Ronald F.; Trescher, William H.; Marcus, Carole L.

    2008-01-01

    Study Objectives: Children with the obstructive sleep apnea syndrome (OSAS) have blunted upper airway responses to negative pressure, but the underlying cause remains unknown. Cortical processing of respiratory afferent information can be tested by measuring respiratory-related evoked potentials (RREPs). We hypothesized that children with OSAS have blunted RREP responses compared to normal children during sleep. Design: During sleep, RREPs were obtained from EEG electrodes Fz, Cz, Pz during stage 2 sleep, slow wave sleep (SWS), and REM sleep. RREPs were produced with multiple short occlusions of the upper airway. Setting: Sleep laboratory. Participants: 9 children with OSAS and 12 normal controls. Measurements and Results: Children with OSAS had significantly decreased evoked K-complex production in stage 2 sleep and slow wave sleep and significantly reduced RREP N350 and P900 components in slow wave sleep. There were no significant differences in any of the measured RREP components in stage 2 sleep, and the only REM difference was decreased P2 amplitude. Conclusions: Results indicate that in children with OSAS, cortical processing of respiratory-related information measured with RREPs persists throughout sleep; however, RREPs during SWS are blunted compared to those seen in control children. Possible causes for this difference include a congenital deficit in neural processing reflective of a predisposition to develop OSAS, or changes in the upper airway rendering the airway less capable of transducing pressure changes following occlusion. Further research is required to evaluate RREPs after effective surgical treatment of OSAS in children, in order to distinguish between these alternatives. Citation: Huang J; Colrain IM; Melendres MC; Karamessinis LR; Pepe ME; Samuel JM; Abi-Raad RF; Trescher WH; Marcus CL. Cortical processing of respiratory afferent stimuli during sleep in children with the obstructive sleep apnea syndrome. SLEEP 2007;31(3):403-410. PMID:18363317

  7. An Automated Simultaneous Recording System for the Pupillary Movement and Unitary Discharge of the Ciliary Nerve in Cats

    NASA Astrophysics Data System (ADS)

    Watanabe, Takeru; Koike, Nobuyuki; Inoue, Takamichi; Kondo, Yasuyuki; Yanagaki, Hidenori; Yasuda, Tetsuya

    1990-02-01

    A computer-automated measuring system was fabricated for real-time, simultaneous data acquisition of the pupillary movement and efferent discharge of the ciliary nerve in animals. For detection of the pupil size, the system incorporates an infrared television camera synchronized by an Apple II computer. It also has an interface circuit which registers the occurrence of nerve impulses and triggers light and electrical stimulators. All the interfaces with the computer were electrically isolated to improve the resistance to noise. A measurement-oriented program was created to provide menudriven commands such as automated measurement, data storage, and data-file load. Simultaneous recordings in the cat have been obtained and are presented for the first time.

  8. Extended secondhand tobacco smoke exposure induces plasticity in nucleus tractus solitarius second-order lung afferent neurons in young guinea pigs.

    PubMed

    Sekizawa, Shin-Ichi; Chen, Chao-Yin; Bechtold, Andrea G; Tabor, Jocelyn M; Bric, John M; Pinkerton, Kent E; Joad, Jesse P; Bonham, Ann C

    2008-08-01

    Infants and young children experiencing extended exposure to secondhand smoke (SHS) have an increased occurrence of asthma, as well as increased cough, wheeze, mucus production and airway hyper-reactivity. Plasticity in lung reflex pathways has been implicated in causing these symptoms, as have changes in substance P-related mechanisms. Using whole-cell voltage-clamp recordings and immunohistochemistry in brainstem slices containing anatomically identified second-order lung afferent nucleus tractus solitarius (NTS) neurons, we determined whether extended SHS exposure during the equivalent period of human childhood modified evoked or spontaneous excitatory synaptic transmission, and whether those modifications were altered by endogenous substance P. SHS exposure enhanced evoked synaptic transmission between sensory afferents and the NTS second-order neurons by eliminating synaptic depression of evoked excitatory postsynaptic currents (eEPSCs), an effect reversed by the neurokinin-1-receptor antagonist (SR140333). The recruitment of substance P in enhancing evoked synaptic transmission was further supported by an increased number of substance P-expressing lung afferent central terminals synapsing onto the second-order lung afferent neurons. SHS exposure did not change background spontaneous EPSCs. The data suggest that substance P in the NTS augments evoked synaptic transmission of lung sensory input following extended exposure to a pollutant. The mechanism may help to explain some of the exaggerated respiratory responses of children exposed to SHS. PMID:18657181

  9. Plasmacytoid dendritic cells migrate in afferent skin lymph.

    PubMed

    Pascale, Florentina; Pascale, Florentia; Contreras, Vanessa; Bonneau, Michel; Courbet, Alexandre; Chilmonczyk, Stefan; Bevilacqua, Claudia; Epardaud, Mathieu; Eparaud, Mathieu; Niborski, Violeta; Riffault, Sabine; Balazuc, Anne-Marie; Foulon, Eliane; Guzylack-Piriou, Laurence; Riteau, Beatrice; Hope, Jayne; Bertho, Nicolas; Charley, Bernard; Schwartz-Cornil, Isabelle

    2008-05-01

    Conventional dendritic cells enter lymph nodes by migrating from peripheral tissues via the lymphatic route, whereas plasmacytoid dendritic cells (pDC), also called IFN-producing cells (IPC), are described to gain nodes from blood via the high endothelial venules. We demonstrate here that IPC/pDC migrate in the afferent lymph of two large mammals. In sheep, injection of type A CpG oligodinucleotide (ODN) induced lymph cells to produce type I IFN. Furthermore, low-density lymph cells collected at steady state produced type I IFN after stimulation with type A CpG ODN and enveloped viruses. Sheep lymph IPC were found within a minor B(neg)CD11c(neg) subset expressing CD45RB. They presented a plasmacytoid morphology, expressed high levels of TLR-7, TLR-9, and IFN regulatory factor 7 mRNA, induced IFN-gamma production in allogeneic CD4(pos) T cells, and differentiated into dendritic cell-like cells under viral stimulation, thus fulfilling criteria of bona fide pDC. In mini-pig, a CD4(pos)SIRP(pos) subset in afferent lymph cells, corresponding to pDC homologs, produced type I IFN after type A CpG-ODN triggering. Thus, pDC can link innate and acquired immunity by migrating from tissue to draining node via lymph, similarly to conventional dendritic cells. PMID:18424716

  10. Microsecond-Scale Timing Precision in Rodent Trigeminal Primary Afferents

    PubMed Central

    Bale, Michael R.; Campagner, Dario; Erskine, Andrew

    2015-01-01

    Communication in the nervous system occurs by spikes: the timing precision with which spikes are fired is a fundamental limit on neural information processing. In sensory systems, spike-timing precision is constrained by first-order neurons. We found that spike-timing precision of trigeminal primary afferents in rats and mice is limited both by stimulus speed and by electrophysiological sampling rate. High-speed video of behaving mice revealed whisker velocities of at least 17,000°/s, so we delivered an ultrafast “ping” (>50,000°/s) to single whiskers and sampled primary afferent activity at 500 kHz. Median spike jitter was 17.4 μs; 29% of neurons had spike jitter < 10 μs. These results indicate that the input stage of the trigeminal pathway has extraordinary spike-timing precision and very high potential information capacity. This timing precision ranks among the highest in biology. PMID:25878266

  11. Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits

    PubMed Central

    Jiang, Yu-Qiu; Zaaimi, Boubker

    2016-01-01

    Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuit-level determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery. SIGNIFICANCE STATEMENT Neuroplasticity is limited in maturity

  12. 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

  13. 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

  14. A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents

    PubMed Central

    Lin, Yu-Jung; Lin, Ruei-Lung; Ruan, Ting; Khosravi, Mehdi

    2014-01-01

    Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are coexpressed in vagal pulmonary C-fiber sensory nerves. Because both these receptors are sensitive to a number of endogenous inflammatory mediators, it is conceivable that they can be activated simultaneously during airway inflammation. This study aimed to determine whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. In anesthetized, spontaneously breathing rats, the reflex-mediated apneic response to intravenous injection of a combined dose of allyl isothiocyanate (AITC, a TRPA1 activator) and capsaicin (Cap, a TRPV1 activator) was ∼202% greater than the mathematical sum of the responses to AITC and Cap when they were administered individually. Similar results were also observed in anesthetized mice. In addition, the synergistic effect was clearly demonstrated when the afferent activity of single vagal pulmonary C-fiber afferents were recorded in anesthetized, artificially ventilated rats; C-fiber responses to AITC, Cap and AITC + Cap (in combination) were 0.6 ± 0.1, 0.8 ± 0.1, and 4.8 ± 0.6 impulses/s (n = 24), respectively. This synergism was absent when either AITC or Cap was replaced by other chemical activators of pulmonary C-fiber afferents. The pronounced potentiating effect was further demonstrated in isolated vagal pulmonary sensory neurons using the Ca2+ imaging technique. In summary, this study showed a distinct positive interaction between TRPA1 and TRPV1 when they were activated simultaneously in pulmonary C-fiber sensory nerves. PMID:25414245

  15. TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.

    PubMed

    Yu, Xiaoyun; Hu, Youtian; Ru, Fei; Kollarik, Marian; Undem, Bradley J; Yu, Shaoyong

    2015-03-15

    Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception. PMID:25591866

  16. The Distribution of Prostaglandins in Afferent and Efferent Lymph From Inflammatory Sites

    PubMed Central

    Johnston, Miles G.; Hay, John B.; Movat, Henry

    1980-01-01

    Arachidonic acid labeled with 14C was injected directly into lymph nodes that had been stimulated at various times with Escherichia coli. The efferent lymph was collected, and labeled catabolites were extracted and analyzed chromatographically. The pimary conversion product recovered was Prostaglandin E2 (PGE2), with the lesser products thromboxane, prostacyclin and prostaglandin F2α (PGF2α) also detected. When the efferent lymph was analyzed by radioimmunoassay after subcutaneous injectino of E coli into the hock, PGE and PGF levels rapidly increased, reached the highest levels in the first 10 hours, and then returned to normal by 24 hours. When the afferent lymph plasma draining inflammatory sites was compared directly with efferent lymph, PGF levels were similar, but the PGE level was always several times higher in the afferent lymph. To examine the catabolism of PG, either 3,H-PGF2ά of 3H-PGE2 was injected into the node, and the efferent lymph plasma was analyzed. No conversion of PGF2α to other products was found. In contrast, catabolic products of PGE2 were detected. With the use of equilibrium dialysis techniques, the binding of PGE2 and PGF2α to proteins in lymph and to bovine serum albumin (BSA), human serum albumin (HSA), and BSA stripped of its fatty acids was established. The binding to lymph proteins correlated with the albumin concentrations in the lymph. This albumin binging probably facilitated the retention and transport of PG in the lymph. PG appears in the lymph at a time corresponding to the uptake and processing of antigen by the node and near the time when lymphokines are detected in lymph and could modulate several steps in the immune response. The PGE detectable in the lymph draining an inflammatory site may play a role in the modulation of blood flow. PMID:6992593

  17. 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.

  18. Afferent connections of the parabrachial nucleus in C57BL/6J mice

    PubMed Central

    Tokita, Kenichi; Inoue, Tomio; Boughter, John D.

    2009-01-01

    Although the mouse is an experimental model with an increasing importance in various fields of Neuroscience, the characteristics of its central gustatory pathways have not yet been well documented. Recent electrophysiological studies using the rat and hamster have revealed that taste processing in the brainstem gustatory relays is under the strong influence of inputs from forebrain gustatory structures. In the present study, we investigated the organization of afferent projections to the mouse parabrachial nucleus (PbN), which is located at a key site between the brainstem and gustatory, viscerosensory and autonomic centers in the forebrain. We made injections of the retrograde tracer Fluorogold centered around the “waist” area of the PbN, whose neurons are known to be highly responsive to taste stimuli. Retrogradely labeled neurons were found in the infralimbic, dysgranular and agranular insular cortex as well as the claustrum; the bed nucleus of the stria terminalis and the substantia innominata; the central nucleus of the amygdala; the lateral and medial preoptic areas, the paraventricular, the dorsomedial, the ventromedial, the arcuate, and the lateral hypothalamic areas; the periaqueductal gray, the substantia nigra pars compacta, and the ventral tegmental area; the supratrigeminal nucleus, rostral and caudal nucleus of the solitary tract; the parvicellular intermediate and gigantocellular reticular nucleus; the caudal and interpolar divisions of the spinal trigeminal nucleus, dorsomedial spinal trigeminal nucleus, and the area postrema. Numbers of labeled neurons in the main components of the gustatory system including the insular cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, lateral hypothalamus, and rostral nucleus of the solitary tract were quantified. These results are basically consistent with those of the previous rat and hamster studies, but some species differences were found. Functional implications of these

  19. Can loss of muscle spindle afferents explain the ataxic gait in Riley–Day syndrome?

    PubMed Central

    Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B.; Kaufmann, Horacio

    2011-01-01

    The Riley–Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10–30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains

  20. Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm

    PubMed Central

    2014-01-01

    Background A peripheral nerve stimulus can enhance or suppress the evoked response to transcranial magnetic stimulation (TMS) depending on the latency of the preceding peripheral nerve stimulation (PNS) pulse. Similarly, somatosensory afference from the passively moving limb can transiently alter corticomotor excitability, in a phase-dependent manner. The repeated association of PNS with TMS is known to modulate corticomotor excitability; however, it is unknown whether repeated passive-movement associative stimulation (MAS) has similar effects. Methods In a proof-of-principle study, using a cross-over design, seven healthy subjects received in separate sessions: (1) TMS (120% of the resting motor threshold-RMT, optimal site for Flexor Carpi Radialis) with muscle at rest; (2) TMS paired with cyclic passive movement during extension cyclic passive movement (400 pairs, 1 Hz), with the intervention order randomly assigned. Normality was tested using the Kolmogorov-Smirnov test, then compared to pre-intervention baseline using repeated measures ANOVA with a Dunnet multiple comparisons test. Results MAS led to a progressive and significant decrease in the motor evoked potential (MEP) amplitude over the intervention (R2 = 0.6665, P < 0.0001), which was not evident with TMS alone (R2 = 0.0068, P = 0.641). Post-intervention excitability reduction, only present with MAS intervention, remained for 20min (0-10min = 68.2 ± 4.9%, P < 0.05; 10-20min = 73.3 ± 9.7%, P < 0.05). Conclusion The association of somatosensory afference from the moving limb with TMS over primary motor cortex in healthy subjects can be used to modulate corticomotor excitability, and may have therapeutic implications. PMID:24597619

  1. Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease–derived stimuli

    PubMed Central

    Hockley, James R.F.; Boundouki, George; Cibert-Goton, Vincent; McGuire, Cian; Yip, Ping K.; Chan, Christopher; Tranter, Michael; Wood, John N.; Nassar, Mohammed A.; Blackshaw, L. Ashley; Aziz, Qasim; Michael, Gregory J.; Baker, Mark D.; Winchester, Wendy J.; Knowles, Charles H.; Bulmer, David C.

    2014-01-01

    Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitization of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9−/− mice. Deletion of NaV1.9 substantially attenuates excitation and subsequent mechanical hypersensitivity after application of inflammatory soup (IS) (bradykinin, ATP, histamine, PGE2, and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9, and there was a rightward shift in stimulus–response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however, run-down of responses to repeat phasic distension were exacerbated in NaV1.9−/− afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9−/− mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics. PMID:24972070

  2. Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling.

    PubMed

    Heppner, Thomas J; Tykocki, Nathan R; Hill-Eubanks, David; Nelson, Mark T

    2016-04-01

    Activation of afferent nerves during urinary bladder (UB) filling conveys the sensation of UB fullness to the central nervous system (CNS). Although this sensory outflow is presumed to reflect graded increases in pressure associated with filling, UBs also exhibit nonvoiding, transient contractions (TCs) that cause small, rapid increases in intravesical pressure. Here, using an ex vivo mouse bladder preparation, we explored the relative contributions of filling pressure and TC-induced pressure transients to sensory nerve stimulation. Continuous UB filling caused an increase in afferent nerve activity composed of a graded increase in baseline activity and activity associated with increases in intravesical pressure produced by TCs. For each ∼4-mmHg pressure increase, filling pressure increased baseline afferent activity by ∼60 action potentials per second. In contrast, a similar pressure elevation induced by a TC evoked an ∼10-fold greater increase in afferent activity. Filling pressure did not affect TC frequency but did increase the TC rate of rise, reflecting a change in the length-tension relationship of detrusor smooth muscle. The frequency of afferent bursts depended on the TC rate of rise and peaked before maximum pressure. Inhibition of small- and large-conductance Ca(2+)-activated K(+)(SK and BK) channels increased TC amplitude and afferent nerve activity. After inhibiting detrusor muscle contractility, simulating the waveform of a TC by gently compressing the bladder evoked similar increases in afferent activity. Notably, afferent activity elicited by simulated TCs was augmented by SK channel inhibition. Our results show that afferent nerve activity evoked by TCs represents the majority of afferent outflow conveyed to the CNS during UB filling and suggest that the maximum TC rate of rise corresponds to an optimal length-tension relationship for efficient UB contraction. Furthermore, our findings implicate SK channels in controlling the gain of sensory

  3. Innate immune pathways in afferent lymph following vaccination with poly(I:C)-containing liposomes.

    PubMed

    Burke, Melissa L; Veer, Michael de; Pleasance, Jill; Neeland, Melanie; Elhay, Martin; Harrison, Paul; Meeusen, Els

    2014-07-01

    Many modern vaccines use defined adjuvants to stimulate the innate immune system and shape the adaptive immune response. The exact nature of these innate signals and whether immune differentiation can originate within the periphery is not known. Here we used an ovine lymphatic cannulation model to characterise the cellular and transcriptomic profile of the afferent lymph following injection of a liposomal vaccine formulation incorporating diphtheria toxoid and the innate stimulator poly(I:C) over a 78-h period. The response to this vaccine featured an early activation of broad pro-inflammatory pathways (e.g. TLR signalling and inflammasome pathways) and the transient recruitment of granulocytes into the lymph. At 24 h a more monocytic cellular profile arose coinciding with a transition to a specific antiviral response characterised by the up-regulation of genes associated with the receptors typical for the viral mimic, poly(I:C) (e.g. TLR3, RIG-I and MDA5). At the latest time points the up-regulation of IL-17A and IL-17F suggested that Th17 cells may participate in the earliest adaptive response to this vaccine. These data provide the most comprehensive picture of the cellular and molecular mechanisms that link the periphery to the draining lymph node following vaccination, and indicate that the immune response is capable of specialising within the periphery. PMID:24045338

  4. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    PubMed Central

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  5. Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater.

    PubMed

    Dux, M; Rosta, J; Sántha, P; Jancsó, G

    2009-07-01

    Neurogenic inflammation of the dura mater encephali has been suggested to contribute to the mechanisms of meningeal nociception and blood flow regulation. Recent findings demonstrated that the rat dura mater is innervated by trigeminal capsaicin-sensitive peptidergic nociceptive afferent nerves which mediate meningeal vascular responses through activation of the transient receptor potential vanilloid type 1 (TRPV1) receptor. The present work explored the functional significance of the capsaicin-sensitive subpopulation of dural afferent nerves via their contribution to the meningeal vascular responses evoked through activation of the proteinase-activated receptor 2 (PAR-2). The vascular responses of the dura mater were studied by laser Doppler flowmetry in a rat open cranial window preparation. Topical applications of trypsin, a PAR-2-activator, or Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)), a selective PAR-2 agonist peptide, resulted in dose-dependent increases in meningeal blood flow. The SLIGRL-NH(2)-induced vasodilatation was significantly reduced following capsaicin-sensitive afferent nerve defunctionalization by prior systemic capsaicin treatment and by pretreatment of the dura mater with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37). Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) an unspecific inhibitor of nitric oxide (NO) production, but not 1-(2-trifluoromethylphenyl) imidazole (TRIM), a neuronal NO synthase inhibitor, also inhibited the vasodilator response to SLIGRL-NH(2). The vasodilator responses elicited by very low concentrations of capsaicin (10 nM) were significantly enhanced by prior application of SLIGRL-NH(2). The present findings demonstrate that activation of the PAR-2 localized on capsaicin-sensitive trigeminal nociceptive afferent nerves induces vasodilatation in the dural vascular bed by mechanisms involving NO and CGRP release. The results indicate that the PAR-2-mediated activation and

  6. Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat.

    PubMed

    Hermes, Sam M; Andresen, Michael C; Aicher, Sue A

    2016-03-01

    The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type. PMID:26706222

  7. Distribution of presumptive chemosensory afferents with FMRFamide- or substance P-like immunoreactivity in decapod crustaceans.

    PubMed

    Schmidt, M

    1997-01-23

    In five species of decapod crustaceans--Cherax destructor (crayfish), Carcinus maenas (crab), Homarus americanus (clawed lobster), Eriocheir sinensis (crab), Macrobrachium rosenbergii (shrimp)--immunocytochemical stainings revealed the presence of sensory afferents with FMRFamide-like immunoreactivity in the central nervous system. These afferents were extremely thin, very numerous, and innervated all sensory neuropils except the optic and olfactory lobes. In their target neuropils they gave rise to condensed net- or ball-like terminal structures. Only in Homarus americanus but not in any other studied species immunocytochemistry revealed a separate, non-overlapping class of sensory afferents with substance P-like immunoreactivity. Also the afferents with substance P-like immunoreactivity were very thin and numerous, innervated all sensory neuropils except optic and olfactory lobes, and gave rise to condensed terminal structures. From their morphological characteristics it can be concluded that likely both classes of afferents are chemosensory. The substance P-like immunoreactivity suggests a link with the nociceptor afferents of vertebrates, with which both classes of afferents share several other morphological features. PMID:9037486

  8. Technetium-99m HIDA hepatobiliary scanning in evaluation of afferent loop syndrome

    SciTech Connect

    Sivelli, R.; Farinon, A.M.; Sianesi, M.; Percudani, M.; Ugolotti, G.; Calbiani, B.

    1984-08-01

    A study of 118 patients, operated on with Billroth II gastrectomy for peptic disease and affected by postgastrectomy syndromes, was carried out. Fifty patients were investigated by means of technetium-99m HIDA hepatobiliary scanning. In 18 patients, in whom an afferent loop syndrome was clinically suspected, hepatobiliary scanning demonstrated an altered afferent loop emptying in 8 and atonic distension of the gallbladder without afferent loop motility changes in 10. Among the patients in the first group, four were treated with a biliary diversion surgical procedure and in the second group, two patients underwent cholecystectomy. Our findings indicate that biliary vomiting, right upper abdominal pain pyrosis, and biliary diarrhea in Billroth II gastrectomized patients are not always pathognomonic symptoms of afferent loop syndrome. Technetium-99m HIDA hepatobiliary scanning represents the only diagnostic means of afferent loop syndrome definition. A differential diagnosis of abnormal afferent loop emptying and gallbladder dyskinesia is necessary for the management planning of these patients, and furthermore, when a surgical treatment is required, biliary diversion with Roux-Y anastomosis or Braun's biliary diversion seems the treatment of choice for afferent loop syndrome, whereas cholecystectomy represents the best procedure for atonic distension of the gallbladder.

  9. 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.

  10. Stimulation of cardiac sympathetic afferents activates glutamatergic neurons in the parabrachial nucleus: relation to neurons containing nNOS.

    PubMed

    Guo, Zhi-Ling; Moazzami, Ali R; Longhurst, John C

    2005-08-16

    Our previous studies have demonstrated that stimulation of cardiac sympathetic afferents activates neurons in the parabrachial nucleus (PBN), a region known to play a role in central integration of cardiovascular autonomic reflexes. However, phenotypes of these activated neurons have not been well identified. Glutamate, an important excitatory neurotransmitter in the brain, is involved in PBN-mediated cardiovascular responses. Recent identification of vesicular glutamate transporter 3 (VGLUT3) has provided a novel and unique marker to locate distinctive perikarya of neurons that use glutamate as a neurotransmitter. The action of glutamate in the brain is influenced by nitric oxide. Thus, using triple immunofluorescent labeling, the present study examined expression of c-Fos, an immediate early gene, in the neurons containing VGLUT3 and neuronal nitric oxide synthase (nNOS) in the PBN following stimulation of cardiac sympathetic afferents. In anesthetized cats with bilateral barodenervation and cervical vagotomy, topical application of bradykinin (BK, 1-10 microg/ml, 50 microl, n = 6) on the left ventricle was performed six times, every 20 min. Repeated administration of BK elicited consistent increases in blood pressure over a 100 min period while no changes were noted in the animals treated with the vehicle for BK (0.9% saline, n=5). Compared to control cats, c-Fos expression was increased significantly in the cell bodies containing VGLUT3 as well as both VGLUT3 and nNOS in the external lateral PBN (elPBN) in BK-treated animals (all P < 0.01). In addition, using similar triple-staining method, we noted that fibers of activated neurons containing nNOS in the elPBN co-localized with vesicular glutamate transporter 2 following BK stimulation. These data suggest that glutamatergic neurons represent a cell type in the PBN that is activated by stimulation of cardiac sympathetic afferents. Nitric oxide has the potential to influence the action of glutamatergic neurons in

  11. Perineural capsaicin induces the uptake and transganglionic transport of choleratoxin B subunit by nociceptive C-fiber primary afferent neurons.

    PubMed

    Oszlács, O; Jancsó, G; Kis, G; Dux, M; Sántha, P

    2015-12-17

    The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain. PMID:26520849

  12. Enterolith Causing Afferent Loop Obstruction: A Case Report and Literature Review

    SciTech Connect

    Lee, Michael C.; Bui, James T.; Knuttinen, M-Grace; Gaba, Ron C.; Scott Helton, W.; Owens, Charles A.

    2009-09-15

    Enterolith formation is a rare cause of afferent limb obstruction following Billroth II gastrectomy and Roux-en-Y hepaticojejunostomy surgery. A case of ascending cholangitis caused by an enterolith incarcerated in the afferent loop of a 15-year-old Roux-en-Y hepaticojejunostomy was emergently decompressed under direct ultrasound guidance prior to surgery. This is the thirteenth reported case of an enterolith causing afferent loop obstruction. A discussion of our management approach and a review of the relevant literature are presented.

  13. Percutaneous jejunostomy through the liver parenchyma for palliation of afferent loop syndrome.

    PubMed

    Kwon, Jae Hyun; Han, Yoon Hee

    2015-01-01

    In the treatment of afferent loop syndrome, jejunostomy or Roux-en-Y gastrojejunostomy have tended to represent the preferred procedures. In patients who are not good candidates for surgery, palliative treatment-i.e., percutaneous transhepatic biliary drainage or percutaneous direct transperitoneal jejunostomy techniques-have been applied. Transhepatic biliary drainage confers a risk of ascending cholangitis. Direct percutaneous transperitoneal drainage may be impractical when overlying bowel loops prevent access to deeply located afferent loops. In the present case, percutaneous jejunostomy through the liver parenchyma was performed successfully for palliation of afferent loop syndrome. PMID:25433418

  14. 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.

  15. GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells.

    PubMed

    Martinez-Monedero, Rodrigo; Liu, Chang; Weisz, Catherine; Vyas, Pankhuri; Fuchs, Paul Albert; Glowatzki, Elisabeth

    2016-01-01

    Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the "empty slots" corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts. PMID:27257620

  16. Type III-IV muscle afferents are not required for steady-state exercise hyperpnea in healthy subjects and patients with COPD or heart failure.

    PubMed

    Poon, Chi-Sang; Song, Gang

    2015-09-15

    Blockade of group III-IV muscle afferents by intrathecal injection of the μ-opioid agonist fentanyl (IF) in humans has been variously reported to depress exercise hyperpnea in some studies but not others. A key unanswered question is whether such an effect is transient or persists in the steady state. Here we show that in healthy subjects undergoing constant-load cycling exercise IF significantly slows the transient exercise ventilatory kinetics but has no discernible effect on the ventilatory response when exercise is sufficiently prolonged. Thus, the ventilatory response to group III-IV muscle afferents input in healthy subjects is not a simple reflex but acts like a high-pass filter with maximum sensitivity during early-phase exercise and is reset in the late phase. In patients with chronic heart failure (CHF) IF causes sustained CO2 retention not only during exercise but also in the resting state, where muscle afferents feedback is minimal. In patients with chronic obstructive pulmonary disease (COPD), IF also elicits sustained decreases in the exercise ventilatory response but with little or no resultant CO2 retention due to concomitant decreases in physiological VD/VT (dead space-to-ventilation ratio). These results support the proposition that optimal long-term regulation of exercise hyperpnea in health and in disease is determined centrally by the respiratory controller through the continuing adaptation of an internal model which dynamically tracks the metabolic CO2 load and the ventilatory inefficiency 1/1-VD/VT that must be overcome for the maintenance of arterial PCO2 homeostasis, rather than being reflexively driven by group III-IV muscle afferents feedback per se. PMID:25911558

  17. Effects of levodropropizine on vagal afferent C-fibres in the cat.

    PubMed Central

    Shams, H.; Daffonchio, L.; Scheid, P.

    1996-01-01

    1. Levodropropizine (LVDP) is an effective antitussive drug. Its effects on single-unit discharge of vagal afferent C-fibres were tested in anaesthetized cats to assess whether an inhibition of vagal C-fibres is involved in its antitussive properties. Vagal C-fibres, identified by their response to phenylbiguanide (PBG), were recorded via suction electrodes from the distal part of the cut vagus. Based on their response to lung inflation, C-fibres were classified as pulmonary (19 fibres) or non-pulmonary (6 fibres). 2. PBG increased the discharge rate of both C-fibre types and activated a respiratory reflex causing apnoea. This reflex was abolished when the second vagus nerve was cut as well, while PBG-mediated stimulation of the C-fibres was not affected by vagotomy. 3. LVDP was administered intravenously and the C-fibre response to PBG was compared with that before administration of the drug. LVDP reduced both the duration of apnoea and the response of the C-fibre to PBG. 4. Comparison of the C-fibre responses to PBG and to a mixture of PBG and LVDP revealed that the period of apnoea was shortened and the discharge rate of the C-fibre reduced when LVDP was present. 5. The LVDP-induced inhibition of the C-fibre response to PBG was on average 50% in pulmonary and 25% in non-pulmonary fibres. 6. These results suggest that LVDP significantly reduces the response of vagal C-fibres to chemical stimuli. It is, thus, likely that the antitussive effect of LVDP is mediated through its inhibitory action on C-fibres. PMID:8851501

  18. Effect of stimulus size and luminance on the rod-, cone-, and melanopsin-mediated pupillary light reflex.

    PubMed

    Park, Jason C; McAnany, J Jason

    2015-01-01

    This study determined if the pupillary light reflex (PLR) driven by brief stimulus presentations can be accounted for by the product of stimulus luminance and area (i.e., corneal flux density, CFD) under conditions biased toward the rod, cone, and melanopsin pathways. Five visually normal subjects participated in the study. Stimuli consisted of 1-s short- and long-wavelength flashes that spanned a large range of luminance and angular subtense. The stimuli were presented in the central visual field in the dark (rod and melanopsin conditions) and against a rod-suppressing short-wavelength background (cone condition). Rod- and cone-mediated PLRs were measured at the maximum constriction after stimulus onset whereas the melanopsin-mediated PLR was measured 5-7 s after stimulus offset. The rod- and melanopsin-mediated PLRs were well accounted for by CFD, such that doubling the stimulus luminance had the same effect on the PLR as doubling the stimulus area. Melanopsin-mediated PLRs were elicited only by short-wavelength, large (>16°) stimuli with luminance greater than 10 cd/m(2), but when present, the melanopsin-mediated PLR was well accounted for by CFD. In contrast, CFD could not account for the cone-mediated PLR because the PLR was approximately independent of stimulus size but strongly dependent on stimulus luminance. These findings highlight important differences in how stimulus luminance and size combine to govern the PLR elicited by brief flashes under rod-, cone-, and melanopsin-mediated conditions. PMID:25788707

  19. Vaccination with liposomal poly(I:C) induces discordant maturation of migratory dendritic cell subsets and anti-viral gene signatures in afferent lymph cells.

    PubMed

    Neeland, Melanie R; Elhay, Martin J; Meeusen, Els N T; de Veer, Michael J

    2014-10-29

    Vaccine formulations administered in the periphery must activate naive immune cells within the lymph node. In this study, we have directly cannulated the ovine lymphatic vessels to investigate the cellular and molecular mechanisms that transfer information from the periphery into the local draining lymph node via the afferent lymph. Inclusion of poly(I:C) into a liposomal vaccine formulation enhances the neutrophil-associated inflammatory immune response in afferent lymph and increases antigen uptake by migratory dendritic cells (DCs). Interestingly, antigen positive migratory DCs undergo discordant maturation, with peak expression of CD86 at 4 h and CD80 at 48-72 h post vaccination. Afferent lymph monocytes up-regulate expression of genes related to inflammatory and anti-viral immune phenotypes following vaccination however show no differentiation into APCs prior to their migration to the local lymph node as measured by surface MHC II expression. Finally, this study reveals the addition of poly(I:C) increases systemic antigen-specific humoral immunity. These findings provide a detailed understanding of the real time in vivo immune response induced by liposomes incorporating the innate immune agonist poly(I:C) utilising a vaccination setting comparable to that administered in humans. PMID:25280435

  20. Two psychophysical channels of whisker deflection in rats align with two neuronal classes of primary afferents.

    PubMed

    Stüttgen, Maik C; Rüter, Johannes; Schwarz, Cornelius

    2006-07-26

    The rat whisker system has evolved into in an excellent model system for sensory processing from the periphery to cortical stages. However, to elucidate how sensory processing finally relates to percepts, methods to assess psychophysical performance pertaining to precise stimulus kinematics are needed. Here, we present a head-fixed, behaving rat preparation that allowed us to measure detectability of a single whisker deflection as a function of amplitude and peak velocity. We found that velocity thresholds for detection of small-amplitude stimuli (<3 degrees) were considerably higher than for detection of large-amplitude stimuli (>3 degrees). This finding suggests the existence of two psychophysical channels mediating detection of whisker deflection: one channel exhibiting high amplitude and low velocity thresholds (W1), and the other channel exhibiting high velocity and low amplitude thresholds (W2). The correspondence of W1 to slowly adapting (SA) and W2 to rapidly adapting (RA) neuronal classes in the trigeminal ganglion was revealed in acute neurophysiological experiments. Neurometric plots of SA and RA cells were closely aligned to psychophysical performance in the corresponding W1 and W2 parameter ranges. Interestingly, neurometric data of SA cells fit the behavior best if it was based on a short time window integrating action potentials during the initial phasic response, in contrast to integrating across the tonic portion of the response. This suggests that detection performance in both channels is based on the assessment of very few spikes in their corresponding groups of primary afferents. PMID:16870738

  1. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    SciTech Connect

    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  2. 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

  3. Influence of map scale on primary afferent terminal field geometry in cat dorsal horn.

    PubMed

    Millecchia, R J; Pubols, L M; Sonty, R V; Culberson, J L; Gladfelter, W E; Brown, P B

    1991-09-01

    1. Thirty-one physiologically identified primary afferent fibers were labeled intracellularly with horseradish peroxidase (HRP). 2. A computer analysis was used to determine whether the distribution of cutaneous mechanoreceptive afferent terminals varies as a function of location within the dorsal horn somatotopic map. 3. An analysis of the geometry of the projections of these afferents has shown that 1) terminal arbors have a greater mediolateral width within the region of the foot representation than lateral to it, 2) terminal arbors have larger length-to-width ratios outside the foot representation than within it, and 3) the orientation of terminal arbors near the boundary of the foot representation reflects the angle of the boundary. Previous attribution of mediolateral width variations to primary afferent type are probably in error, although there appear to be genuine variations of longitudinal extent as a function of primary afferent type. 4. Nonuniform terminal distributions represent the first of a three-component process underlying assembly of the monosynaptic portions of cell receptive fields (RFs) and the somatotopic map. The other two components consist of the elaboration of cell dendritic trees and the establishment of selective connections. 5. The variation of primary afferent terminal distributions with map location is not an absolute requirement for development of the map; for example, the RFs of postsynaptic cells could be assembled with the use of a uniform terminal distribution for all afferents, everywhere in the map, as long as cell dendrites penetrate the appropriate portions of the presynaptic neuropil and receive connections only from afferent axons contributing to their RFs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1753281

  4. 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. PMID:25012715

  5. 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.

  6. Control of arousal through neuropeptide afferents of the locus coeruleus.

    PubMed

    Zitnik, Gerard A

    2016-06-15

    The locus coeruleus-norepinephine (LC-NE) system is implicated in mediating several aspects of arousal. Alterations in LC neuronal discharge is associated with distinct changes in behavior, cognition, sensory processing and regulation of the sleep-wake cycle. Changes in LC output and subsequent release of NE in target brain regions help adjust arousal state to respond appropriately to environmental conditions and behavioral circumstances. One way in which LC activity is controlled is through release of endogenous neuropeptides. Based on the sleep-wake cycle and environmental cues specific neuropeptide afferent systems are activated, innervating the LC. These neuropeptides include: corticotropin releasing factor (CRF), orexin (ORX), endogenous opioids, substance P (SP), melanin-concentrating hormone (MCH), neuropeptide Y (NPY) and somatostatin (SS). This review summarizes studies examining the neuroanatomical projections of these neuropeptides, their receptors in the LC, the actions on LC neurons and downstream NE release, as well as the behavioral and cognitive effects associated individual neuropeptide-mediated innervation of the LC. Finally, the relationship between individual neuropeptides, the LC-NE system and various clinical disorders is discussed, providing evidence for possible therapeutic targets for treatment of several arousal- and stress-related disorders. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26688115

  7. Coarse topographic organization of pheromone-sensitive afferents from different antennal surfaces in the American cockroach.

    PubMed

    Nishino, Hiroshi; Watanabe, Hidehiro; Kamimura, Itsuro; Yokohari, Fumio; Mizunami, Makoto

    2015-05-19

    In contrast to visual, auditory, taste, and mechanosensory neuropils, in which sensory afferents are topographically organized on the basis of their peripheral soma locations, axons of cognate sensory neurons from different locations of the olfactory sense organ converge onto a small spherical neuropil (glomerulus) in the first-order olfactory center. In the cockroach Periplaneta americana, sex pheromone-sensitive afferents with somata in the antero-dorsal and postero-ventral surfaces of a long whip-like antenna are biased toward the anterior and posterior regions of a macroglomerulus, respectively. In each region, afferents with somata in the more proximal antenna project to more proximal region, relative to the axonal entry points. However, precise topography of afferents in the macroglomerulus has remained unknown. Using single and multiple neuronal stainings, we showed that afferents arising from anterior, dorsal, ventral and posterior surfaces of the proximal regions of an antenna were biased progressively from the anterior to posterior region of the macroglomerulus, reflecting chiasmatic axonal re-arrangements that occur immediately before entering the antennal lobe. Morphologies of individual afferents originating from the proximal antenna matched results of mass neuronal stainings, but their three-dimensional origins in the antenna were hardly predictable on the basis of the projection patterns. Such projection biases made by neuronal populations differ from strict somatotopic projections of antennal mechanosensory neurons in the same species, suggesting a unique sensory mechanism to process information about odor location and direction on a single antenna. PMID:25849528

  8. The role of the renal afferent and efferent nerve fibers in heart failure

    PubMed Central

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  9. Retinal transplants can drive a pupillary reflex in host rat brains.

    PubMed Central

    Klassen, H; Lund, R D

    1987-01-01

    Retinae taken from embryonic rats were transplanted over the midbrain of neonatal rats, from whom one eye had been removed. After 5 months, the optic nerve of the remaining eye was cut, and the transplant was exposed. Illumination of the transplant caused pupilloconstriction of the host eye, a response abolished by damaging the transplant. Thus neural transplants are capable of driving specific reflexes in response to natural stimuli. Images PMID:3477821

  10. Cortical afferents to the smooth-pursuit region of the macaque monkey's frontal eye field.

    PubMed

    Stanton, Gregory B; Friedman, Harriet R; Dias, Elisa C; Bruce, Charles J

    2005-08-01

    In primates, the frontal eye field (FEF) contains separate representations of saccadic and smooth-pursuit eye movements. The smooth-pursuit region (FEFsem) in macaque monkeys lies principally in the fundus and deep posterior wall of the arcuate sulcus, between the FEF saccade region (FEFsac) in the anterior wall and somatomotor areas on the posterior wall and convexity. In this study, cortical afferents to FEFsem were mapped by injecting retrograde tracers (WGA-HRP and fast blue) into electrophysiologically identified FEFsem sites in two monkeys. In the frontal lobe, labeled neurons were found mostly on the ipsilateral side in the (1) supplementary eye field region and lateral area F7; (2) area F2 along the superior limb of the arcuate sulcus; and (3) in the buried cortex of the arcuate sulcus extending along the superior and inferior limbs and including FEFsac and adjacent areas 8, 45, and PMv. Labeled cells were also found in the caudal periprincipal cortex (area 46) in one monkey. Labeled cells were found bilaterally in the frontal lobe in the deep posterior walls of the arcuate sulcus and postarcuate spurs and in cingulate motor areas 24 and 24c. In postcentral cortical areas all labeling was ipsilateral and there were two major foci of labeled cells: (1) the depths of the intraparietal sulcus including areas VIP, LIP, and PEa, and (2) the anterior wall and fundus of the superior temporal sulcus including areas PP and MST. Smaller numbers of labeled cells were found in superior temporal sulcal areas FST, MT, and STP, posterior cingulate area 23b, area 3a within the central sulcus, areas SII, RI, Tpt in the lateral sulcus, and parietal areas 7a, 7b, PEc, MIP, DP, and V3A. Many of these posterior afferent cortical areas code visual-motion (MT, MST, and FST) or visual-motion and vestibular (PP, VIP) signals, consistent with the responses of neurons in FEFsem and with the overall physiology and anatomy of the smooth-pursuit eye movement system. PMID:15940495

  11. Effect of synthetic cationic protein on mechanoexcitability of vagal afferent nerve subtypes in guinea pig esophagus.

    PubMed

    Yu, Shaoyong; Ouyang, Ann

    2011-12-01

    Eosinophilic esophagitis is characterized by increased infiltration and degranulation of eosinophils in the esophagus. Whether eosinophil-derived cationic proteins regulate esophageal sensory nerve function is still unknown. Using synthetic cationic protein to investigate such effect, we performed extracellular recordings from vagal nodose or jugular neurons in ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were determined by comparing action potentials evoked by esophageal distensions before and after perfusion of synthetic cationic protein poly-L-lysine (PLL) with or without pretreatment with poly-L-glutamic acid (PLGA), which neutralized cationic charges of PLL. Perfusion with PLL did not evoke action potentials in esophageal nodose C fibers but increased their responses to esophageal distension. This potentiation effect lasted for 30 min after washing out of PLL. Pretreatment with PLGA significantly inhibited PLL-induced mechanohyperexcitability of esophageal nodose C fibers. In esophageal nodose Aδ fibers, perfusion with PLL did not evoke action potentials. In contrast to nodose C fibers, both the spontaneous discharges and the responses to esophageal distension in nodose Aδ fibers were decreased by perfusion with PLL, which can be restored after washing out PLL for 30-60 min. Pretreatment with PLGA attenuated PLL-induced decrease in spontaneous discharge and mechanoexcitability of esophageal nodose Aδ fibers. In esophageal jugular C fibers, PLL neither evoked action potentials nor changed their responses to esophageal distension. Collectively, these data demonstrated that synthetic cationic protein did not evoke action potential discharges of esophageal vagal afferents but had distinctive sensitization effects on their responses to esophageal distension. PMID:21960520

  12. Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study.

    PubMed

    Ferreri, Florinda; Ponzo, David; Hukkanen, Taina; Mervaala, Esa; Könönen, Mervi; Pasqualetti, Patrizio; Vecchio, Fabrizio; Rossini, Paolo Maria; Määttä, Sara

    2012-07-01

    When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition. PMID:22457460

  13. [Postsynaptic reactions of cerebral cortex neurons, activated by nociceptive afferents during stimulation of the Raphe nuclei].

    PubMed

    Labakhua, T Sh; Dzhanashiia, T K; Gedevanishvili, G I; Dzhokhadze, L D; Tkemaladze, T T; Abzianidze, I V

    2012-01-01

    On cats, we studied the influence of stimulation of the Raphe nuclei (RN) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulation of the ventroposteromedial--VPN--nucleus of the thalamus) afferent inputs. 6 cells, selectively excited by stimulation of nocciceptors and 9 cells, activated by both the above nociceptive and non-nociceptive influences (nociceptive and convergent neurons, respectively) were recorded intracellular. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the letter of significant duration, up to 200-300 ms) compleх. Conditioning stimulation of the RN which preceded test stimulus applied to the tooth pulp or VPM nucleus by 100 to 800 ms, induced 40-60 % decrease of the IPSP amplitude only, while maхimal effect of influence, in both cases, was noted within intervals of 300-800 ms between conditioning and test stimulus. During stimulation of the RN, serotonin released via receptor and second messengers, provides postsynaptic modulation of GABAergic system, decreasing the IPSP amplitude which occurs after stimulation of both the tooth pulp and VPM thalamic nucleus. This process may be realized trough either pre- or postsynaptic mechanisms. PMID:22392784

  14. Identification and function of adenosine A3 receptor in afferent arterioles.

    PubMed

    Lu, Yan; Zhang, Rui; Ge, Ying; Carlstrom, Mattias; Wang, Shaohui; Fu, Yiling; Cheng, Liang; Wei, Jin; Roman, Richard J; Wang, Lei; Gao, Xichun; Liu, Ruisheng

    2015-05-01

    Adenosine plays an important role in regulation of renal microcirculation. All receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney. However, little is known about the location and function of the A3 receptor in the kidney. The present study determined the expression and role of A3 receptors in mediating the afferent arteriole (Af-Art) response and studied the interaction of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art. We found that the A3 receptor expressed in microdissected isolated Af-Art and the mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art, A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3 receptor dilated the preconstricted Af-Art by norepinephrine and blunted the vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had no effect on A3 receptor agonist-induced vasodilation, indicating that the dilatory effect of A3 receptor activation is not mediated by activation of A2 receptor. We conclude that the A3 receptor is expressed in the Af-Art, and activation of the A3 receptor dilates the Af-Art. PMID:25608966

  15. Cortical and subcortical plasticity in the brains of humans, primates, and rats after damage to sensory afferents in the dorsal columns of the spinal cord

    PubMed Central

    Kaas, Jon H.; Qi, Hui-Xin; Burish, Mark; Gharbawie, Omar; Onifer, Stephen M.; Massey, James M.

    2008-01-01

    The failure of injured axons to regenerate following spinal cord injury deprives brain neurons of their normal sources of activation. These injuries also result in the reorganization of affected areas of the central nervous system that is thought to drive both the ensuing recovery of function and the formation of maladaptive neuronal circuitry. Better understanding of the physiological consequences of novel synaptic connections produced by injury and the mechanisms that control their formation are important to the development of new successful strategies for the treatment of patients with spinal cord injuries. Here we discuss the anatomical, physiological and behavioral changes that take place in response to injury-induced plasticity after damage to the dorsal column pathway in rats and monkeys. Complete section of the dorsal columns of the spinal cord at a high cervical level in monkeys and rats interrupts the ascending axon branches of low threshold mechanoreceptor afferents subserving the forelimb and the rest of the lower body. Such lesions render the corresponding part of the somatotopic representation of primary somatosensory cortex totally unresponsive to tactile stimuli. There are also behavioral consequences of the sensory loss, including an impaired use of the hand/forelimb in manipulating small objects. In monkeys, if some of the afferents from the hand remain intact after dorsal column lesions, these remaining afferents extensively reactivate portions of somatosensory cortex formerly representing the hand. This functional reorganization develops over a postoperative period of one month, during which hand use rapidly improves. These recoveries appear to be mediated, at least in part, by the sprouting of preserved afferents within the cuneate nucleus of the dorsal column-trigeminal complex. In rats, such functional collateral sprouting has been promoted by the post-lesion digestion of the perineuronal net in the cuneate nucleus. Thus, this and other

  16. The degree of acute descending control of spinal nociception in an area of primary hyperalgesia is dependent on the peripheral domain of afferent input

    PubMed Central

    Drake, Robert A R; Hulse, Richard P; Lumb, Bridget M; Donaldson, Lucy F

    2014-01-01

    Descending controls of spinal nociceptive processing play a critical role in the development of inflammatory hyperalgesia. Acute peripheral nociceptor sensitization drives spinal sensitization and activates spino–supraspinal–spinal loops leading to descending inhibitory and facilitatory controls of spinal neuronal activity that further modify the extent and degree of the pain state. The afferent inputs from hairy and glabrous skin are distinct with respect to both the profile of primary afferent classes and the degree of their peripheral sensitization. It is not known whether these differences in afferent input differentially engage descending control systems to different extents or in different ways. Injection of complete Freund's adjuvant resulted in inflammation and swelling of hairy hind foot skin in rats, a transient thermal hyperalgesia lasting <2 h, and longlasting primary mechanical hyperalgesia (≥7 days). Much longer lasting thermal hyperalgesia was apparent in glabrous skin (1 h to >72 h). In hairy skin, transient hyperalgesia was associated with sensitization of withdrawal reflexes to thermal activation of either A- or C-nociceptors. The transience of the hyperalgesia was attributable to a rapidly engaged descending inhibitory noradrenergic mechanism, which affected withdrawal responses to both A- and C-nociceptor activation and this could be reversed by intrathecal administration of yohimbine (α-2-adrenoceptor antagonist). In glabrous skin, yohimbine had no effect on an equivalent thermal inflammatory hyperalgesia. We conclude that acute inflammation and peripheral nociceptor sensitization in hind foot hairy skin, but not glabrous skin, rapidly activates a descending inhibitory noradrenergic system. This may result from differences in the engagement of descending control systems following sensitization of different primary afferent classes that innervate glabrous and hairy skin. PMID:24879873

  17. Role played by NaV 1.7 channels on thin-fiber muscle afferents in transmitting the exercise pressor reflex.

    PubMed

    Stone, Audrey J; Copp, Steven W; Kaufman, Marc P

    2015-11-15

    Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of somatic afferent neurons and are thought to play an important role in the signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than 300 nM. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels in the transmission of muscle afferent input evoking the exercise pressor reflex. We first showed that the exercise pressor reflex, which was evoked by static contraction of the triceps surae muscles, was reversibly attenuated by application of 50 nM TTX, but not 5 nM TTX, to the L4-L5 dorsal roots (control: 21 ± 1 mmHg, TTX: 8 ± 2 mmHg, recovery: 21 ± 3 mmHg; n = 6; P < 0.01). We next found that the peak pressor responses to contraction were significantly attenuated by dorsal root application of 100 nM Ssm6a, a compound that is a selective NaV 1.7 channel inhibitor. Removal of Ssm6a restored the reflex to its control level (control: 19 ± 3 mmHg, Ssm6a: 10 ± 1 mmHg, recovery: 19 ± 4 mmHg; n = 6; P < 0.05). Compound action potentials recorded from the L4 and L5 dorsal roots and evoked by single-pulse stimulation of the sciatic nerve showed that both TTX and Ssm6a attenuated input from group III, as well as group IV afferents. We conclude that NaV 1.7 channels play a role in the thin-fiber muscle afferent pathway evoking the exercise pressor reflex. PMID:26310938

  18. Facilitation of motor evoked potentials by somatosensory afferent stimulation.

    PubMed

    Deletis, V; Schild, J H; Berić, A; Dimitrijević, M R

    1992-10-01

    The effect of an electrically induced peripheral afferent volley upon electrical and magnetic motor evoked potentials (MEPs) from muscles of the upper and lower extremities was studied in 16 healthy volunteers. A standard conditioning-test (C-T) paradigm was employed whereby the test stimulus (transcranial electric or magnetic) was applied at random time intervals, from 10 msec prior to 90 msec after the conditioning stimulus (peripheral nerve stimulus). MEP amplitude facilitation was observed for the majority of the upper extremity muscles tested at two distinct periods, one occurring at short, and the other at long C-T intervals. This bimodal trend of MEP facilitation was found to be equally as prominent in the lower extremity muscles tested. The period of short C-T interval facilitation is consistent with modifications in the spinal excitability of the segmental motoneuron pool. On the other hand, the period of long C-T interval facilitation is suggested to be due to alterations in excitability of the motor cortex as a result of the arrival of the orthodromic sensory volley. Although most pronounced in muscles innervated by the nerve to which the conditioning stimulus was applied, this bimodal facilitatory effect was also observed in adjacent muscles not innervated by the stimulated nerve. Qualitatively, the conditioned MEPs from the upper and lower extremities responded similarly to both electrical and magnetic trans-cranial stimulation. In addition, our study demonstrates that the C-T paradigm has potential for use in the assessment of spinal and cortical sensorimotor integration by providing quantitative information which cannot be obtained through isolated assessment of sensory and/or motor pathways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1385090

  19. Sensitivity to communicative and non-communicative gestures in adolescents and adults with autism spectrum disorder: saccadic and pupillary responses.

    PubMed

    Aldaqre, Iyad; Schuwerk, Tobias; Daum, Moritz M; Sodian, Beate; Paulus, Markus

    2016-09-01

    Nonverbal communication using social cues, like gestures, governs a great part of our daily interactions. It has been proposed that people with autism spectrum disorder (ASD) show a deviant processing of social cues throughout their social cognitive development. However, social cues do not always convey an intention to communicate. Hence, the aim of this study was to test the sensitivity of adolescents and adults with ASD and neurotypical controls to social cues of high communicative (pointing) and low communicative values (grasping). For this purpose, we employed a spatial cueing paradigm with both Cue Types and compared saccadic reaction times (SRTs) between conditions in which the target appeared at a location which was congruent versus incongruent with the direction of the cue. Results showed that both adolescents and adults with ASD had slower SRTs for the incongruent relative to the congruent condition for both Cue Types, reflecting sensitivity to these cues. Additionally, mental effort during the processing of these social cues was assessed by means of pupil dilation. This analysis revealed that, while individuals with and without ASD required more mental effort to process incongruent compared to the congruent cues, cues with higher communicative value posed more processing load for the ASD group. These findings suggest that the perception of social gestures is intact in ASD but requires additional mental effort for gestures with higher communicative value. PMID:27119361

  20. Endoscopic management of afferent loop syndrome after a pylorus preserving pancreatoduodenecotomy presenting with obstructive jaundice and ascending cholangitis.

    PubMed

    Kim, Jae Kyung; Park, Chan Hyuk; Huh, Ji Hye; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Chung, Jaebock; Bang, Seungmin

    2011-09-01

    Afferent loop syndrome is a rare complication of gastrojejunostomy. Patients usually present with abdominal distention and bilious vomiting. Afferent loop syndrome in patients who have undergone a pylorus preserving pancreaticoduodenectomy can present with ascending cholangitis. This condition is related to a large volume of reflux through the biliary-enteric anastomosis and static materials with bacterial overgrowth in the afferent loop. Patients with afferent loop syndrome after pylorus preserving pancreaticoduodenectomy frequently cannot be confirmed as surgical candidates due to poor medical condition. In that situation, a non-surgical palliation should be considered. Herein, we report two patients with afferent loop syndrome presenting with obstructive jaundice and ascending cholangitis. The patients suffered from the recurrence of pancreatic cancer after pylorus preserving pancreaticoduodenectomy. The diagnosis of afferent loop syndrome was confirmed, and the patients were successfully treated by inserting an endoscopic metal stent using a colonoscopic endoscope. PMID:22741115

  1. Pupillary and Heart Rate Reactivity in Children with Minimal Brain Dysfunction

    ERIC Educational Resources Information Center

    Zahn, Theodore P.; And Others

    1978-01-01

    In an attempt to replicate and extend previous findings on autonomic arousal and responsivity in children with minimal brain dysfunction (MBD), pupil size, heart rate, skin conductance, and skin temperature were recorded from 32 MBD and 45 control children (6-13 years old). (Author/CL)

  2. 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

  3. 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

  4. 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

  5. Investigation of the isoplanatic patch and wavefront aberration along the pupillary axis compared to the line of sight in the eye

    PubMed Central

    Nowakowski, Maciej; Sheehan, Matthew; Neal, Daniel; Goncharov, Alexander V.

    2012-01-01

    Conventional optical systems usually provide best image quality on axis, while showing unavoidable gradual decrease in image quality towards the periphery of the field. The optical system of the human eye is not an exception. Within a limiting boundary the image quality can be considered invariant with field angle, and this region is known as the isoplanatic patch. We investigate the isoplanatic patch of eight healthy eyes and measure the wavefront aberration along the pupillary axis compared to the line of sight. The results are used to discuss methods of ocular aberration correction in wide-field retinal imaging with particular application to multi-conjugate adaptive optics systems. PMID:22312578

  6. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

    PubMed Central

    Bagot, Rosemary C.; Parise, Eric M.; Peña, Catherine J.; Zhang, Hong-Xing; Maze, Ian; Chaudhury, Dipesh; Persaud, Brianna; Cachope, Roger; Bolaños-Guzmán, Carlos A.; Cheer, Joseph; Deisseroth, Karl; Han, Ming-Hu; Nestler, Eric J.

    2015-01-01

    Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression. PMID:25952660

  7. The regularity of primary and secondary muscle spindle afferent discharges

    PubMed Central

    Matthews, P. B. C.; Stein, R. B.

    1969-01-01

    1. The patterns of nerve impulses in the afferent fibres from muscle spindles have been studied using the soleus muscle of the decerebrate cat. Impulses from up to five single units were recorded simultaneously on magnetic tape, while the muscle was stretched to a series of different lengths. Various statistics were later determined by computer analysis. 2. After the ventral roots were cut to eliminate any motor outflow to the muscle spindles, both primary and secondary spindle endings discharged very regularly. At frequencies around 30 impulses/sec the coefficient of variation of the interspike interval distributions had a mean value of only 0·02 for the secondary endings and 0·058 for the primary endings. The values obtained for the two kinds of ending did not overlap. 3. When the ventral roots were intact, the `spontaneous' fusimotor activity considerably increased the variability of both kinds of endings. Secondary endings still discharged much more regularly than primary endings, even when the fusimotor activity increased the frequency of firing equally for the two kinds of endings. At frequencies around 30/sec the average coefficient of variation of the interval distributions was then 0·064 for the secondary endings and 0·25 for the primary endings. 4. When the ventral roots were intact there was usually an inverse relation between the values of successive interspike intervals. The first serial correlation coefficient often had values down to - 0·6 for both kinds of ending. Higher order serial correlation coefficients were also computed. 5. Approximate calculations, based on the variability observed when the ventral roots were intact, suggested that when the length of the muscle was constant an observer analysing a 1 sec period of discharge from a single primary ending would only be able to distinguish about six different lengths of the muscle. The corresponding figure for a secondary ending was twenty-five lengths. 6. The increase in variability with

  8. Electrophysiology of the afferent innervation of the penis of the domestic ram.

    PubMed Central

    Cottrell, D F; Iggo, A; Kitchell, R L

    1978-01-01

    1. The discharge of impulses in afferent fibres dissected from the dorsal nerve of the penis of chloralose-anaesthetized rams was recorded electrophysiologically during controlled natural stimulation of the surgically exposed penis maintained at body temperature and mechanically stabilized in a plaster of Paris mould. 2. Fifty-eight slowly adapting mechanorecptor units were examined and their pressure, velocity and displacement thresholds were determined. Units often responded best to integumental stretch. Few had resting discharges. During a sustained perpendicularly applied displacement most units adapted to silence within 1.5 min. The units were classified into types from an analysis of their adapted impulse trains in response to a sustained mechanical stimulus. 3. Twenty-five mechanoreceptive units had rapidly adapting responses. Most units had typical rapid adapting characteristics and discharged impulses only during the dynamic phase of the application of the displacement. A subgroup had intermediate adapting characteristics, and discharged intermittently during steady displacement of the integument. 4. The mechanical sensitivity of most receptors altered when the temperature of the receptive field was changed with a positive correlation in eleven units, a negative correlation in six. Six slowly adapting units were thermally insensitive. Twelve rapidly adapting units were tested. Six had a positive thermal correlation and four a negative correlation. 5. The conduction velocities of axons of mechanoreceptor units in the dorsal nerve of the penis were in the Aalpha range (12--77 msec-1). 6. Two specific warm and five specific cold units were found. The conduction velocities of the axons supplying warm receptors were 45.4 msec-1 (one unit) and those for cold receptors were 7.5, 7.8, 30, 45.5, 48.7 msec-1. 7. No correlation could be found between the receptor submodality and the profuse receptor end bulb population demonstrated histologically. PMID:722579

  9. Effects of afferent volleys from the limbs on the discharge patterns of interpositus neurones in cats anaesthetized with alpha-chloralose.

    PubMed Central

    Armstrong, D M; Cogdell, B; Harvey, R

    1975-01-01

    that the short latency responses of the interpositus neurones were a result of synaptic excitation via cerebellar afferents, while the ensuing inhibition was a result of post-synaptic inhibition resulting from the Purkinje cell excitation due to the afferent volleys. It is suggested that the long latency excitation is due to the afferent volleys. It is suggested that the long latency excitation is due at least in part to disinhibition resulting from long pauses in Purkinje cell firing following their activation by climbing fibre afferents. 9. The possibility that these long latency responses have a physiological significance in relation to locomotion is discussed. PMID:1151794

  10. 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

  11. Structure of the Afferent Terminals in Terminal Ganglion of a Cricket and Persistent Homology

    PubMed Central

    Brown, Jacob; Gedeon, Tomáš

    2012-01-01

    We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals) into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets. PMID:22649516

  12. 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

  13. Quantitative analysis of pupillary light reflex by real-time autofluorescent imaging in a diabetic mouse model.

    PubMed

    Kumar, Saravana; Zhuo, Lang

    2011-03-01

    Here we (i) introduce a novel laser-based quantitative method of measuring pupillary light reflex (PLR) and applied it for the in vivo PLR monitoring of early diabetic retinopathy (DR) in a mouse model, (ii) investigate if melanopsin-expressing retinal ganglion cells (mRGCs) are implicated in the early progression of DR and, if so, is there an impact on PLR and (iii) determine if changes in PLR precede the onset of retinal hypoperfusion. A base-line PLR measurement is captured from C57BL/6J wild type mice followed by a single intraperitoneal administration of 200 mg/kg streptozotocin (STZ) and citrate buffer (vehicle) for the "diabetic" (n=5) and "control" (n=5) mice respectively, the very next day. PLR measurements are repeated once a week for four weeks. The PLR data comprises retinal autofluorescence intensity (AFI) values sampled over a 5-min period under confocal excitation with 488 nm high intensity blue laser light. AFI is used here as an indirect measure of pupil size since the amount of excitation light entering and emission light leaving the eye is proportional to the pupil area. Immunohistochemistry (IHC) staining of mRGCs and RT-PCR of melanopsin mRNA are performed at the end-point. The vascular calibre of both control and STZ-treated diabetic mice is assessed via in vivo fluorescein angiography (FA) on day 0 (base-line), 1/2, 1 and 4 months post-STZ treatment. The PLR profile shows a more rapid pupil constriction and slower dilation in diabetic mice compared to the control. Changes in PLR coincide or even precede the onset of retinal hypoperfusion. Extensive dendritic network of the mRGCs in retinal whole-mounts and increased melanopsin mRNA from the whole eye are also observed in diabetic mice. These pathological changes to mRGCs during early DR may in turn contribute towards changes in PLR. We present here a quantitative method of measuring PLR which enables an early detection of DR with potential application in the clinical setting. In contrast to

  14. High Frequency Stimulation of the Subthalamic Nucleus Leads to Presynaptic GABA(B)-Dependent Depression of Subthalamo-Nigral Afferents

    PubMed Central

    Dvorzhak, Anton; Gertler, Christoph; Harnack, Daniel; Grantyn, Rosemarie

    2013-01-01

    Patients with akinesia benefit from chronic high frequency stimulation (HFS) of the subthalamic nucleus (STN). Among the mechanisms contributing to the therapeutic success of HFS-STN might be a suppression of activity in the output region of the basal ganglia. Indeed, recordings in the substantia nigra pars reticulata (SNr) of fully adult mice revealed that HFS-STN consistently produced a reduction of compound glutamatergic excitatory postsynaptic currents at a time when the tetrodotoxin-sensitive components of the local field potentials had already recovered after the high frequency activation. These observations suggest that HFS-STN not only alters action potential conduction on the way towards the SNr but also modifies synaptic transmission within the SNr. A classical conditioning-test paradigm was then designed to better separate the causes from the indicators of synaptic depression. A bipolar platinum-iridium macroelectrode delivered conditioning HFS trains to a larger group of fibers in the STN, while a separate high-ohmic glass micropipette in the rostral SNr provided test stimuli at minimal intensity to single fibers. The conditioning-test interval was set to 100 ms, i.e. the time required to recover the excitability of subthalamo-nigral axons after HFS-STN. The continuity of STN axons passing from the conditioning to the test sites was examined by an action potential occlusion test. About two thirds of the subthalamo-nigral afferents were occlusion-negative, i.e. they were not among the fibers directly activated by the conditioning STN stimulation. Nonetheless, occlusion-negative afferents exhibited signs of presynaptic depression that could be eliminated by blocking GABA(B) receptors with CGP55845 (1 µM). Further analysis of single fiber-activated responses supported the proposal that the heterosynaptic depression of synaptic glutamate release during and after HFS-STN is mainly caused by the tonic release of GABA from co-activated striato

  15. 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

  16. Vagal afferent innervation of the rat fundic stomach: morphological characterization of the gastric tension receptor.

    PubMed

    Berthoud, H R; Powley, T L

    1992-05-01

    Although the gastric tension receptor has been characterized behaviorally and electrophysiologically quite well, its location and structure remains elusive. Therefore, the vagal afferents to the rat fundus (forestomach or nonglandular stomach) were anterogradely labeled in vivo with injections of the carbocyanine dye Dil into the nodose ganglia, and the nerves and ganglia of the enteric nervous system were labeled in toto with intraperitoneal Fluorogold injection. Dissected layers and cryostat cross sections of the fundic wall were mounted in glycerin and analyzed by means of conventional and laser scanning confocal microscopy. Particularly in the longitudinal, and to a lesser extent in the circular, smooth muscle layers, Dil-labeled fibers and terminals were abundant. These processes, which originated from fibers coursing through the myenteric ganglia and connectives, entered either muscle coat and then ran parallel to the respective muscle fibers, often for several millimeters. They ran in close association with the Fluorogold-labeled network of interstitial cells of Cajal, upon which they appeared to form multiple spiny appositions or varicosities. In the myenteric plexus, two different types of afferent vagal structures were observed. Up to 300 highly arborizing endings forming dense accumulations of small puncta similar to the esophageal intraganglionic laminar endings (Rodrigo et al., '75 Acta Anat. 92:79-100) were found in the fundic wall ipsilateral to the injected nodose ganglion. They often covered small clusters of myenteric neurons or even single isolated ganglion cells (mean = 5.8 neurons) and tended to extend throughout the neuropil of the ganglia. In a second pattern, fine varicose fibers with less profuse arborizations innervated mainly the central regions of myenteric ganglia. Camera lucida analyses established that single vagal afferent fibers had separate collaterals in both a smooth muscle layer and the myenteric ganglia. Finally, Dil

  17. The Dynamics of Voluntary Force Production in Afferented Muscle Influence Involuntary Tremor.

    PubMed

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

    2016-01-01

    Voluntary control of force is always marked by some degree of error and unsteadiness. Both neural and mechanical factors contribute to these fluctuations, but how they interact to produce them is poorly understood. In this study, we identify and characterize a previously undescribed neuromechanical interaction where the dynamics of voluntary force production suffice to generate involuntary tremor. Specifically, participants were asked to produce isometric force with the index finger and use visual feedback to track a sinusoidal target spanning 5-9% of each individual's maximal voluntary force level. Force fluctuations and EMG activity over the flexor digitorum superficialis (FDS) muscle were recorded and their frequency content was analyzed as a function of target phase. Force variability in either the 1-5 or 6-15 Hz frequency ranges tended to be largest at the peaks and valleys of the target sinusoid. In those same periods, FDS EMG activity was synchronized with force fluctuations. We then constructed a physiologically-realistic computer simulation in which a muscle-tendon complex was set inside of a feedback-driven control loop. Surprisingly, the model sufficed to produce phase-dependent modulation of tremor similar to that observed in humans. Further, the gain of afferent feedback from muscle spindles was critical for appropriately amplifying and shaping this tremor. We suggest that the experimentally-induced tremor may represent the response of a viscoelastic muscle-tendon system to dynamic drive, and therefore does not fall into known categories of tremor generation, such as tremorogenic descending drive, stretch-reflex loop oscillations, motor unit behavior, or mechanical resonance. Our findings motivate future efforts to understand tremor from a perspective that considers neuromechanical coupling within the context of closed-loop control. The strategy of combining experimental recordings with physiologically-sound simulations will enable thorough exploration

  18. The Dynamics of Voluntary Force Production in Afferented Muscle Influence Involuntary Tremor

    PubMed Central

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

    2016-01-01

    Voluntary control of force is always marked by some degree of error and unsteadiness. Both neural and mechanical factors contribute to these fluctuations, but how they interact to produce them is poorly understood. In this study, we identify and characterize a previously undescribed neuromechanical interaction where the dynamics of voluntary force production suffice to generate involuntary tremor. Specifically, participants were asked to produce isometric force with the index finger and use visual feedback to track a sinusoidal target spanning 5–9% of each individual's maximal voluntary force level. Force fluctuations and EMG activity over the flexor digitorum superficialis (FDS) muscle were recorded and their frequency content was analyzed as a function of target phase. Force variability in either the 1–5 or 6–15 Hz frequency ranges tended to be largest at the peaks and valleys of the target sinusoid. In those same periods, FDS EMG activity was synchronized with force fluctuations. We then constructed a physiologically-realistic computer simulation in which a muscle-tendon complex was set inside of a feedback-driven control loop. Surprisingly, the model sufficed to produce phase-dependent modulation of tremor similar to that observed in humans. Further, the gain of afferent feedback from muscle spindles was critical for appropriately amplifying and shaping this tremor. We suggest that the experimentally-induced tremor may represent the response of a viscoelastic muscle-tendon system to dynamic drive, and therefore does not fall into known categories of tremor generation, such as tremorogenic descending drive, stretch-reflex loop oscillations, motor unit behavior, or mechanical resonance. Our findings motivate future efforts to understand tremor from a perspective that considers neuromechanical coupling within the context of closed-loop control. The strategy of combining experimental recordings with physiologically-sound simulations will enable thorough

  19. Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

    PubMed

    Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

    2016-07-01

    Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. PMID:27052583

  20. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion. II. Phase asymmetry

    PubMed Central

    Spardy, Lucy E.; Markin, Sergey N.; Shevtsova, Natalia A.; Prilutsky, Boris I.; Rybak, Ilya A.; Rubin, Jonathan E.

    2012-01-01

    We analyze a closed loop neuromechanical model of locomotor rhythm generation. The model is composed of a spinal central pattern generator (CPG) and a single-joint limb, with CPG outputs projecting via motoneurons to muscles that control the limb and afferent signals from the muscles feeding back to the CPG. In a preceding companion paper, we analyzed how the model generates oscillations in the presence or absence of feedback, identified curves in a phase plane associated with the limb that signify where feedback levels induce phase transitions within the CPG, and explained how increasing feedback strength restores oscillations in a model representation of spinal cord injury; from these steps, we derived insights about features of locomotor rhythms in several scenarios and made predictions about rhythm responses to various perturbations. In this paper, we exploit our analytical observations to construct a reduced model that retains important characteristics from the original system. We prove the existence of an oscillatory solution to the reduced model using a novel version of a Melnikov function, adapted for discontinuous systems and also comment on the uniqueness and stability of this solution. Our analysis yields a deeper understanding of how the model must be tuned to generate oscillations and how the details of the limb dynamics shape overall model behavior. In particular, we explain how, due to the feedback signals in the model, changes in the strength of a tonic supra-spinal drive to the CPG yield asymmetric alterations in the durations of different locomotor phases, despite symmetry within the CPG itself. PMID:22058275

  1. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: II. Phase asymmetry.

    PubMed

    Spardy, Lucy E; Markin, Sergey N; Shevtsova, Natalia A; Prilutsky, Boris I; Rybak, Ilya A; Rubin, Jonathan E

    2011-12-01

    In this paper we analyze a closed loop neuromechanical model of locomotor rhythm generation. The model is composed of a spinal central pattern generator (CPG) and a single-joint limb, with CPG outputs projecting via motoneurons to muscles that control the limb and afferent signals from the muscles feeding back to the CPG. In a preceding companion paper (Spardy et al 2011 J. Neural Eng. 8 065003), we analyzed how the model generates oscillations in the presence or absence of feedback, identified curves in a phase plane associated with the limb that signify where feedback levels induce phase transitions within the CPG, and explained how increasing feedback strength restores oscillations in a model representation of spinal cord injury; from these steps, we derived insights about features of locomotor rhythms in several scenarios and made predictions about rhythm responses to various perturbations. In this paper, we exploit our analytical observations to construct a reduced model that retains important characteristics from the original system. We prove the existence of an oscillatory solution to the reduced model using a novel version of a Melnikov function, adapted for discontinuous systems, and also comment on the uniqueness and stability of this solution. Our analysis yields a deeper understanding of how the model must be tuned to generate oscillations and how the details of the limb dynamics shape overall model behavior. In particular, we explain how, due to the feedback signals in the model, changes in the strength of a tonic supra-spinal drive to the CPG yield asymmetric alterations in the durations of different locomotor phases, despite symmetry within the CPG itself. PMID:22058275

  2. Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity

    PubMed Central

    Saku, Keita; Kishi, Takuya; Sakamoto, Kazuo; Hosokawa, Kazuya; Sakamoto, Takafumi; Murayama, Yoshinori; Kakino, Takamori; Ikeda, Masataka; Ide, Tomomi; Sunagawa, Kenji

    2014-01-01

    Abstract It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague–Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was ‐28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex. PMID:25194023

  3. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: II. Phase asymmetry

    NASA Astrophysics Data System (ADS)

    Spardy, Lucy E.; Markin, Sergey N.; Shevtsova, Natalia A.; Prilutsky, Boris I.; Rybak, Ilya A.; Rubin, Jonathan E.

    2011-10-01

    In this paper we analyze a closed loop neuromechanical model of locomotor rhythm generation. The model is composed of a spinal central pattern generator (CPG) and a single-joint limb, with CPG outputs projecting via motoneurons to muscles that control the limb and afferent signals from the muscles feeding back to the CPG. In a preceding companion paper (Spardy et al 2011 J. Neural Eng. 8 065003), we analyzed how the model generates oscillations in the presence or absence of feedback, identified curves in a phase plane associated with the limb that signify where feedback levels induce phase transitions within the CPG, and explained how increasing feedback strength restores oscillations in a model representation of spinal cord injury; from these steps, we derived insights about features of locomotor rhythms in several scenarios and made predictions about rhythm responses to various perturbations. In this paper, we exploit our analytical observations to construct a reduced model that retains important characteristics from the original system. We prove the existence of an oscillatory solution to the reduced model using a novel version of a Melnikov function, adapted for discontinuous systems, and also comment on the uniqueness and stability of this solution. Our analysis yields a deeper understanding of how the model must be tuned to generate oscillations and how the details of the limb dynamics shape overall model behavior. In particular, we explain how, due to the feedback signals in the model, changes in the strength of a tonic supra-spinal drive to the CPG yield asymmetric alterations in the durations of different locomotor phases, despite symmetry within the CPG itself.

  4. 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. PMID:25591867

  5. Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing

    PubMed Central

    Hickman, Tyler T.; Liberman, M. Charles

    2015-01-01

    Normal hearing requires proper differentiation of afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) that carry acoustic information to the brain. Within individual IHCs, presynaptic ribbons show a size gradient with larger ribbons on the modiolar face and smaller ribbons on the pillar face. This structural gradient is associated with a gradient of spontaneous rates and threshold sensitivity, which is essential for a wide dynamic range of hearing. Despite their importance for hearing, mechanisms that direct ribbon differentiation are poorly defined. We recently identified adenomatous polyposis coli protein (APC) as a key regulator of interneuronal synapse maturation. Here, we show that APC is required for ribbon size heterogeneity and normal cochlear function. Compared with wild-type littermates, APC conditional knock-out (cKO) mice exhibit decreased auditory brainstem responses. The IHC ribbon size gradient is also perturbed. Whereas the normal-developing IHCs display ribbon size gradients before hearing onset, ribbon sizes are aberrant in APC cKOs from neonatal ages on. Reporter expression studies show that the CaMKII-Cre used to delete the floxed APC gene is present in efferent olivocochlear (OC) neurons, not IHCs or SGNs. APC loss led to increased volumes and numbers of OC inhibitory dopaminergic boutons on neonatal SGN fibers. Our findings identify APC in efferent OC neurons as essential for regulating ribbon heterogeneity, dopaminergic terminal differentiation, and cochlear sensitivity. This APC effect on auditory epithelial cell synapses resembles interneuronal and nerve–muscle synapses, thereby defining a global role for APC in synaptic maturation in diverse cell types. Significance Statement This study identifies novel molecules and cellular interactions that are essential for the proper maturation of afferent ribbon synapses in sensory cells of the inner ear, and for normal hearing. PMID:26085645

  6. Whole-brain mapping of afferent projections to the bed nucleus of the stria terminalis in tree shrews.

    PubMed

    Ni, Rong-Jun; Luo, Peng-Hao; Shu, Yu-Mian; Chen, Ju-Tao; Zhou, Jiang-Ning

    2016-10-01

    The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. The aim of the present study was to investigate the sources of afferent projections to the BST throughout the brain of tree shrews using the retrograde tracer Fluoro-Gold (FG). The present results provide the first detailed whole-brain mapping of BST-projecting neurons in the tree shrew brain. The BST was densely innervated by the prefrontal cortex, entorhinal cortex, ventral subiculum, amygdala, ventral tegmental area, and parabrachial nucleus. Moreover, moderate projections to the BST originated from the medial preoptic area, supramammillary nucleus, paraventricular thalamic nucleus, pedunculopontine tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and nucleus of the solitary tract. Afferent projections to the BST are identified in the ventral pallidum, nucleus of the diagonal band, ventral posteromedial thalamic nucleus, posterior complex of the thalamus, interfascicular nucleus, retrorubral field, rhabdoid nucleus, intermediate reticular nucleus, and parvicellular reticular nucleus. In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal. PMID:27436534

  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. Identification of bladder and colon afferents in the nodose ganglia of male rats.

    PubMed

    Herrity, April N; Rau, Kristofer K; Petruska, Jeffrey C; Stirling, David P; Hubscher, Charles H

    2014-11-01

    The sensory neurons innervating the urinary bladder and distal colon project to similar regions of the central nervous system and often are affected simultaneously by various diseases and disorders, including spinal cord injury. Anatomical and physiological commonalities between the two organs involve the participation of shared spinally derived pathways, allowing mechanisms of communication between the bladder and colon. Prior electrophysiological data from our laboratory suggest that the bladder also may receive sensory innervation from a nonspinal source through the vagus nerve, which innervates the distal colon as well. The present study therefore aimed to determine whether anatomical evidence exists for vagal innervation of the male rat urinary bladder and to assess whether those vagal afferents also innervate the colon. Additionally, the relative contribution to bladder and colon sensory innervation of spinal and vagal sources was determined. By using lipophilic tracers, neurons that innervated the bladder and colon in both the nodose ganglia (NG) and L6/S1 and L1/L2 dorsal root ganglia (DRG) were quantified. Some single vagal and spinal neurons provided dual innervation to both organs. The proportions of NG afferents labeled from the bladder did not differ from spinal afferents labeled from the bladder when considering the collective population of total neurons from either group. Our results demonstrate evidence for vagal innervation of the bladder and colon and suggest that dichotomizing vagal afferents may provide a neural mechanism for cross-talk between the organs. PMID:24845615

  9. Afferent control of locomotor CPG: insights from a simple neuromechanical model.

    PubMed

    Markin, Sergey N; Klishko, Alexander N; Shevtsova, Natalia A; Lemay, Michel A; Prilutsky, Boris I; Rybak, Ilya A

    2010-06-01

    A simple neuromechanical model has been developed that describes a spinal central pattern generator (CPG) controlling the locomotor movement of a single-joint limb via activation of two antagonist (flexor and extensor) muscles. The limb performs rhythmic movements under control of the muscular, gravitational and ground reaction forces. Muscle afferents provide length-dependent (types Ia and II) and force-dependent (type Ib from the extensor) feedback to the CPG. We show that afferent feedback adjusts CPG operation to the kinematics and dynamics of the limb providing stable "locomotion." Increasing the supraspinal drive to the CPG increases locomotion speed by reducing the duration of stance phase. We show that such asymmetric, extensor-dominated control of locomotor speed (with relatively constant swing duration) is provided by afferent feedback independent of the asymmetric rhythmic pattern generated by the CPG alone (in "fictive locomotion" conditions). Finally, we demonstrate the possibility of reestablishing stable locomotion after removal of the supraspinal drive (associated with spinal cord injury) by increasing the weights of afferent inputs to the CPG, which is thought to occur following locomotor training. PMID:20536917

  10. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion. I. Rhythm generation

    PubMed Central

    Spardy, Lucy E.; Markin, Sergey N.; Shevtsova, Natalia A.; Prilutsky, Boris I.; Rybak, Ilya A.; Rubin, Jonathan E.

    2012-01-01

    Locomotion in mammals is controlled by a spinal central pattern generator (CPG) coupled to a biomechanical limb system, with afferent feedback to the spinal circuits and CPG closing the control loop. We have considered a simplified model of this system, in which the CPG establishes a rhythm when a supra-spinal activating drive is present and afferent signals from a single-joint limb feed back to affect CPG operation. Using dynamical systems methods, in a series of two papers, we analyze the mechanisms by which this model produces oscillations, and the characteristics of these oscillations, in the closed and open loop regimes. In this first paper, we analyze the phase transition mechanisms operating within the CPG and use the results to explain how afferent feedback allows oscillations to occur at a wider range of drive values to the CPG than the range over which oscillations occur in the CPG without feedback and to comment on why stronger feedback leads to faster oscillations. Linking these transitions to structure in the phase plane associated with the limb segment clarifies how increased weights of afferent feedback to the CPG can restore locomotion after removal of supra-spinal drive to simulate spinal cord injury. PMID:22058274

  11. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: I. Rhythm generation.

    PubMed

    Spardy, Lucy E; Markin, Sergey N; Shevtsova, Natalia A; Prilutsky, Boris I; Rybak, Ilya A; Rubin, Jonathan E

    2011-12-01

    Locomotion in mammals is controlled by a spinal central pattern generator (CPG) coupled to a biomechanical limb system, with afferent feedback to the spinal circuits and CPG closing the control loop. We have considered a simplified model of this system, in which the CPG establishes a rhythm when a supra-spinal activating drive is present and afferent signals from a single-joint limb feed back to affect CPG operation. Using dynamical system methods, in a series of two papers we analyze the mechanisms by which this model produces oscillations, and the characteristics of these oscillations, in the closed- and open-loop regimes. In this first paper, we analyze the phase transition mechanisms operating within the CPG and use the results to explain how afferent feedback allows oscillations to occur at a wider range of drive values to the CPG than the range over which oscillations occur in the CPG without feedback, and then to comment on why stronger feedback leads to faster oscillations. Linking these transitions to structures in the phase plane associated with the limb segment clarifies how increased weights of afferent feedback to the CPG can restore locomotion after removal of supra-spinal drive to simulate spinal cord injury. PMID:22058274

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

    PubMed

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

    2016-06-15

    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, such as 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 deselection 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. J. Comp. Neurol. 524:1892-1919, 2016. © 2016 Wiley Periodicals, Inc. PMID:26660356

  13. A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: I. Rhythm generation

    NASA Astrophysics Data System (ADS)

    Spardy, Lucy E.; Markin, Sergey N.; Shevtsova, Natalia A.; Prilutsky, Boris I.; Rybak, Ilya A.; Rubin, Jonathan E.

    2011-10-01

    Locomotion in mammals is controlled by a spinal central pattern generator (CPG) coupled to a biomechanical limb system, with afferent feedback to the spinal circuits and CPG closing the control loop. We have considered a simplified model of this system, in which the CPG establishes a rhythm when a supra-spinal activating drive is present and afferent signals from a single-joint limb feed back to affect CPG operation. Using dynamical system methods, in a series of two papers we analyze the mechanisms by which this model produces oscillations, and the characteristics of these oscillations, in the closed- and open-loop regimes. In this first paper, we analyze the phase transition mechanisms operating within the CPG and use the results to explain how afferent feedback allows oscillations to occur at a wider range of drive values to the CPG than the range over which oscillations occur in the CPG without feedback, and then to comment on why stronger feedback leads to faster oscillations. Linking these transitions to structures in the phase plane associated with the limb segment clarifies how increased weights of afferent feedback to the CPG can restore locomotion after removal of supra-spinal drive to simulate spinal cord injury.

  14. Pre-Synaptic Inhibition of Afferent Feedback in the Macaque Spinal Cord Does Not Modulate with Cycles of Peripheral Oscillations Around 10 Hz

    PubMed Central

    Galán, Ferran; Baker, Stuart N.

    2015-01-01

    Spinal interneurons are partially phase-locked to physiological tremor around 10 Hz. The phase of spinal interneuron activity is approximately opposite to descending drive to motoneurons, leading to partial phase cancellation and tremor reduction. Pre-synaptic inhibition of afferent feedback modulates during voluntary movements, but it is not known whether it tracks more rapid fluctuations in motor output such as during tremor. In this study, dorsal root potentials (DRPs) were recorded from the C8 and T1 roots in two macaque monkeys following intra-spinal micro-stimulation (random inter-stimulus interval 1.5–2.5 s, 30–100 μA), whilst the animals performed an index finger flexion task which elicited peripheral oscillations around 10 Hz. Forty one responses were identified with latency < 5 ms; these were narrow (mean width 0.59 ms), and likely resulted from antidromic activation of afferents following stimulation near terminals. Significant modulation during task performance occurred in 16/41 responses, reflecting terminal excitability changes generated by pre-synaptic inhibition (Wall's excitability test). Stimuli falling during large-amplitude 8–12 Hz oscillations in finger acceleration were extracted, and sub-averages of DRPs constructed for stimuli delivered at different oscillation phases. Although some apparent phase-dependent modulation was seen, this was not above the level expected by chance. We conclude that, although terminal excitability reflecting pre-synaptic inhibition of afferents modulates over the timescale of a voluntary movement, it does not follow more rapid changes in motor output. This suggests that pre-synaptic inhibition is not part of the spinal systems for tremor reduction described previously, and that it plays a role in overall—but not moment-by-moment—regulation of feedback gain. PMID:26635536

  15. Pupillary efficient lighting system

    DOEpatents

    Berman, Samuel M.; Jewett, Don L.

    1991-01-01

    A lighting system having at least two independent lighting subsystems each with a different ratio of scotopic illumination to photopic illumination. The radiant energy in the visible region of the spectrum of the lighting subsystems can be adjusted relative to each other so that the total scotopic illumination of the combined system and the total photopic illumination of the combined system can be varied independently. The dilation or contraction of the pupil of an eye is controlled by the level of scotopic illumination and because the scotopic and photopic illumination can be separately controlled, the system allows the pupil size to be varied independently of the level of photopic illumination. Hence, the vision process can be improved for a given level of photopic illumination.

  16. Intraspinal sprouting of unmyelinated pelvic afferents after complete spinal cord injury is correlated with autonomic dysreflexia induced by visceral pain

    PubMed Central

    Hou, Shaoping; Duale, Hanad; Rabchevsky, Alexander G.

    2012-01-01

    Autonomic dysreflexia is a potentially life-threatening hypertensive syndrome following high thoracic (T) spinal cord injury (SCI). It is commonly triggered by noxious pelvic stimuli below the injury site that correlates with increased sprouting of primary afferent C-fibers into the lumbosacral spinal cord. We have recently demonstrated that injury-induced plasticity of lumbosacral propriospinal neurons, which relay pelvic visceral sensations to thoracolumbar sympathetic preganglionic neurons, is also correlated with the development of this syndrome. To determine the phenotype of pelvic afferent fiber sprouts after SCI, cholera toxin subunit beta (CTb) was injected into the distal colon 2 weeks post T4 transection/sham to label colonic visceral afferents. After 1 week transport, the lumbosacral spinal cords were cryosectioned and immunohistochemically stained for CTb, the nociceptive-specific marker calcitonin gene-related peptide (CGRP), and the myelinated fiber marker RT97. Quantitative analysis showed that the density of CGRP+ afferent fibers was significantly increased in the L6/S1 dorsal horns of T4-transected versus sham rats, whereas RT97+ afferent fiber density showed no change. Importantly, CTb-labeled pelvic afferent fibers were co-localized with CGRP+ fibers, but not with RT97+ fibers. These results suggest that the sprouting of unmyelinated nociceptive pelvic afferents following high thoracic SCI, but not myelinated fibers, contributes to hypertensive autonomic dysreflexia induced by pelvic visceral pain. PMID:19146928

  17. 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. PMID:27019197

  18. Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli

    PubMed Central

    Bráz, João M.; Basbaum, Allan I.

    2010-01-01

    Although transgenic and knockout mice have helped delineate the mechanisms of action of diverse noxious compounds, it is still difficult to determine unequivocally the subpopulations of primary afferent nociceptor that these molecules engage. As most noxious stimuli lead to tissue and/or nerve injury, here we used induction of activating transcription factor 3 (ATF3), a reliable marker of nerve injury, to assess the populations of primary afferent fibers that are activated after peripheral administration of noxious chemical stimuli. In wild-type mice, hindpaw injections of capsaicin, formalin, mustard oil or menthol induce expression of ATF3 in distinct subpopulations of sensory neurons. Interestingly, even though these noxious chemicals are thought to act through subtypes of transient receptor potential (TRP) channels, all compounds also induced ATF3 in neurons that appear not to express the expected TRP channel subtypes. On the other hand, capsaicin failed to induce ATF3 in mice lacking TRPV1, indicating that TRPV1 is required for both the direct and indirect induction of ATF3 in sensory neurons. By contrast, only low doses of formalin or mustard oil failed to induce ATF3 in TRPA1 null mice, indicating that injections of high doses (>0.5%) of formalin or mustard oil recruit both TRPA1 and non-TRPA1 expressing primary afferent fibers. Finally, peripheral injection of menthol, a TRPM8 receptor agonist, induced ATF3 in a wide variety of sensory neurons, but in a TRPM8-independent manner. We conclude that purportedly selective agonists can activate a heterogeneous population of sensory neurons, which ultimately could contribute to the behavioral responses evoked. PMID:20605331

  19. Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat.

    PubMed Central

    Baker, D G; Coleridge, H M; Coleridge, J C; Nerdrum, T

    1980-01-01

    1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain. 2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd--5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 . 1--1 . 0 microgram/ml.) locally to the site of the ending; we also injected bradykinin (0 . 3--1 . 0 microgram/kg) into the left atrium. 3. Afferent endings excited by bradykinin (159 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with A delta of C fibres (mean conduction velocity, 7 . 5 +/- 0 . 6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume. 4. Bradykinin increased mechanoreceptor firing from 0 . 7 +/- to 5 . 0 +/- 0 . 3 (mean +/- S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle. 5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A delta fibres (mean conduction velocity, 2 . 3 +/- 0 . 7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0 . 6 to 15 . 6 +/- 1 . 3 impulses/sec and

  20. Temporal Dynamics of L5 Dendrites in Medial Prefrontal Cortex Regulate Integration Versus Coincidence Detection of Afferent Inputs

    PubMed Central

    Zemelman, Boris V.; Johnston, Daniel

    2015-01-01

    Distinct brain regions are highly interconnected via long-range projections. How this inter-regional communication occurs depends not only upon which subsets of postsynaptic neurons receive input, but also, and equally importantly, upon what cellular subcompartments the projections target. Neocortical pyramidal neurons receive input onto their apical dendrites. However, physiological characterization of these inputs thus far has been exclusively somatocentric, leaving how the dendrites respond to spatial and temporal patterns of input unexplored. Here we used a combination of optogenetics with multisite electrode recordings to simultaneously measure dendritic and somatic responses to afferent fiber activation in two different populations of layer 5 (L5) pyramidal neurons in the rat medial prefrontal cortex (mPFC). We found that commissural inputs evoked monosynaptic responses in both intratelencephalic (IT) and pyramidal tract (PT) dendrites, whereas monosynaptic hippocampal input primarily targeted IT, but not PT, dendrites. To understand the role of dendritic integration in the processing of long-range inputs, we used dynamic clamp to simulate synaptic currents in the dendrites. IT dendrites functioned as temporal integrators that were particularly responsive to dendritic inputs within the gamma frequency range (40–140 Hz). In contrast, PT dendrites acted as coincidence detectors by responding to spatially distributed signals within a narrow time window. Thus, the PFC extracts information from different brain regions through the combination of selective dendritic targeting and the distinct dendritic physiological properties of L5 pyramidal dendrites. PMID:25788669

  1. Divergence in Endothelin-1- and Bradykinin-Activated Store-Operated Calcium Entry in Afferent Sensory Neurons

    PubMed Central

    Szteyn, Kalina; Gomez, Ruben; Berg, Kelly A

    2015-01-01

    Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal through Gαq/11-protein coupled receptors (GPCRs) to produce nociceptor sensitization and pain. Both peptides activate phospholipase C to stimulate Ca2+ accumulation, diacylglycerol production, and protein kinase C activation and are rapidly desensitized via a G-protein receptor kinase 2-dependent mechanism. However, ET-1 produces a greater response and longer lasting nocifensive behavior than BK in multiple models, indicating a potentially divergent signaling mechanism in primary afferent sensory neurons. Using cultured sensory neurons, we demonstrate significant differences in both Ca2+ influx and Ca2+ release from intracellular stores following ET-1 and BK treatments. As intracellular store depletion may contribute to the regulation of other signaling cascades downstream of GPCRs, we concentrated our investigation on store-operated Ca2+ channels. Using pharmacological approaches, we identified transient receptor potential canonical channel 3 (TRPC3) as a dominant contributor to Ca2+ influx subsequent to ET-1 treatment. On the other hand, BK treatment stimulated Orai1 activation, with only minor input from TRPC3. Taken together, data presented here suggest that ET-1 signaling targets TRPC3, generating a prolonged Ca2+ signal that perpetuates nocifensive responses. In contrast, Orai1 dominates as the downstream target of BK receptor activation and results in transient intracellular Ca2+ increases and abridged nocifensive responses. PMID:25873305

  2. GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells123

    PubMed Central

    Martinez-Monedero, Rodrigo

    2016-01-01

    Abstract Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many “ribbonless” afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the “empty slots” corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts. PMID:27257620

  3. Opioids inhibit visceral afferent activation of catecholamine neurons in the solitary tract nucleus.

    PubMed

    Cui, R J; Roberts, B L; Zhao, H; Andresen, M C; Appleyard, S M

    2012-10-11

    Brainstem A2/C2 catecholamine (CA) neurons within the solitary tract nucleus (NTS) influence many homeostatic functions, including food intake, stress, respiratory and cardiovascular reflexes. They also play a role in both opioid reward and withdrawal. Injections of opioids into the NTS modulate many autonomic functions influenced by catecholamine neurons including food intake and cardiac function. We recently showed that NTS-CA neurons are directly activated by incoming visceral afferent inputs. Here we determined whether opioid agonists modulate afferent activation of NTS-CA neurons using transgenic mice with EGFP expressed under the control of the tyrosine hydroxylase promoter (TH-EGFP) to identify catecholamine neurons. The opioid agonist Met-enkephalin (Met-Enk) significantly attenuated solitary tract-evoked excitatory postsynaptic currents (ST-EPSCs) in NTS TH-EGFP neurons by 80%, an effect reversed by wash or the mu opioid receptor-specific antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP). Met-Enk had a significantly greater effect to inhibit afferent inputs onto TH-EGFP-positive neurons than EGFP-negative neurons, which were only inhibited by 50%. The mu agonist, DAMGO, also inhibited the ST-EPSC in TH-EGFP neurons in a dose-dependent manner. In contrast, neither the delta agonist DPDPE, nor the kappa agonist, U69,593, consistently inhibited the ST-EPSC amplitude. Met-Enk and DAMGO increased the paired pulse ratio, decreased the frequency, but not amplitude, of mini-EPSCs and had no effect on holding current, input resistance or current-voltage relationships in TH-EGFP neurons, suggesting a presynaptic mechanism of action on afferent terminals. Met-Enk significantly reduced both the basal firing rate of NTS TH-EGFP neurons and the ability of afferent stimulation to evoke an action potential. These results suggest that opioids inhibit NTS-CA neurons by reducing an excitatory afferent drive onto these neurons through presynaptic inhibition of

  4. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization.

    PubMed

    Ford, Anthony P

    2012-02-01

    Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers

  5. Firing of antagonist small-diameter muscle afferents reduces voluntary activation and torque of elbow flexors.

    PubMed

    Kennedy, David S; McNeil, Chris J; Gandevia, Simon C; Taylor, Janet L

    2013-07-15

    During muscle fatigue, firing of small-diameter muscle afferents can decrease voluntary activation of the fatigued muscle. However, these afferents may have a more widespread effect on other muscles in the exercising limb. We examined if the firing of fatigue-sensitive afferents from elbow extensor muscles in the same arm reduces torque production and voluntary activation of elbow flexors. In nine subjects we examined voluntary activation of elbow flexors by measuring changes in superimposed twitches evoked by transcranial magnetic stimulation of the motor cortex during brief (2-3 s) maximal voluntary contractions (MVC). Inflation of a blood pressure cuff following a 2-min sustained MVC blocked blood flow to the fatigued muscle and maintained firing of small-diameter afferents. After a fatiguing elbow flexion contraction, maximal flexion torque was lower (26.0 ± 4.4% versus 67.9 ± 5.2% of initial maximal torque; means ± s.d.; P < 0.001) and superimposed twitches were larger (4.1 ± 1.1% versus 1.8 ± 0.2% ongoing MVC, P = 0.01) with than without ischaemia. After a fatiguing elbow extensor contraction, maximal flexion torque was also reduced (82.2 ± 4.9% versus 91.4 ± 2.3% of initial maximal torque; P = 0.007), superimposed twitches were larger (2.7 ± 0.7% versus 1.3 ± 0.2% ongoing MVC; P = 0.02) and voluntary activation lower (81.6 ± 8.2% versus 95.5 ± 6.9%; P = 0.04) with than without ischaemia. After a fatiguing contraction, voluntary drive to the fatigued muscles is reduced with continued input from small-diameter muscle afferents. Furthermore, fatigue of the elbow extensor muscles decreases voluntary drive to unfatigued elbow flexors of the same arm. Therefore, firing of small-diameter muscle afferents from one muscle can affect voluntary activation and hence torque generation of another muscle in the same limb. PMID:23652589

  6. Primary afferents with TRPM8 and TRPA1 profiles target distinct subpopulations of rat superficial dorsal horn neurones

    PubMed Central

    Wrigley, Paul J; Jeong, Hyo-Jin; Vaughan, Christopher W

    2009-01-01

    Background and purpose: The transient receptor potential (TRP) channels, transient receptor potential melastatin-1 (TRPM8) and transient receptor potential ankyrin-1 (TRPA1), are expressed in subpopulations of sensory neurones and have been proposed to mediate innocuous and noxious cold sensation respectively. The aim of this study was to compare TRPM8 and TRPA1 modulation of glutamatergic afferent transmission within the spinal dorsal horn. Experimental approach: Whole cell patch clamp recordings were made from rat spinal cord slices in vitro to examine the effect of TRP agonists and temperature on glutamatergic excitatory postsynaptic currents (EPSCs). Key results: Icilin (3 or 100 µmol·L−1), menthol (200 µmol·L−1) and capsaicin (1 µmol·L−1) reduced the amplitude of primary afferent evoked EPSCs in subpopulations of lamina I and II neurones. In a subpopulation of superficial neurones, innocuous cold (threshold 29°C), 3 µmol·L−1 icilin (EC50 1.5 µmol·L−1) and menthol (EC50 263 µmol·L−1) increased the rate of spontaneous miniature EPSCs. In the majority of lamina I and II neurones, 100 µmol·L−1 icilin (EC50 79 µmol·L−1), allyl isothiocyanate (EC50 226 µmol·L−1), cinnamaldehyde (EC50 38 µmol·L−1) and capsaicin (1 µmol·L−1) increased miniature EPSC rate. The response to 100 µmol·L−1, but not 3 µmol·L−1 icilin, was abolished by ruthenium red, while neither was affected by iodoresiniferatoxin. Responsiveness to 3 µmol·L−1, but not to 100 µmol·L−1 icilin, was highly predictive of innocuous cold responsiveness. Neurones responding to 3 µmol·L−1 icilin and innocuous cold were located more superficially than those responding to 100 µmol·L−1 icilin. Conclusions and implications: Activation of TRPM8 and TRPA1 presynaptically modulated glutamatergic transmission onto partially overlapping but distinct populations of superficial dorsal horn neurones. Spinal TRPM8 and TRPA1 channels may therefore provide

  7. Reliable detection of predator cues in afferent spike trains of a katydid under high background noise levels

    PubMed Central

    Hartbauer, Manfred; Radspieler, Gerald; Römer, Heiner

    2014-01-01

    SUMMARY Katydid receivers face the problem of detecting behaviourally relevant predatory cues from echolocating bats in the same frequency domain as their own conspecific mating signals. We therefore tested the hypothesis that katydids are able to detect the presence of insectivorous bats in spike discharges at early stages of nervous processing in the auditory pathway by using the temporal details characteristic for responses to echolocation sequences. Spike activity was recorded from an identified nerve cell (omega neuron) under both laboratory and field conditions. In the laboratory, the preparation was stimulated with sequences of bat calls at different repetition rates typical for the guild of insectivorous bats, in the presence of background noise. The omega cell fired brief high-frequency bursts of action potentials in response to each bat sound pulse. Repetition rates of 18 and 24 Hz of these pulses resulted in a suppression of activity resulting from background noise, thus facilitating the detection of bat calls. The spike activity typical for responses to bat echolocation contrasts to responses to background noise, producing different distributions of inter-spike intervals. This allowed development of a ‘neuronal bat detector’ algorithm, optimized to detect responses to bats in afferent spike trains. The algorithm was applied to more than 24 hours of outdoor omega-recordings performed either at a rainforest clearing with high bat activity or in rainforest understory, where bat activity was low. In 95% of cases, the algorithm detected a bat reliably, even under high background noise, and correctly rejected responses when an electronic bat detector showed no response. PMID:20709932

  8. Reliable detection of predator cues in afferent spike trains of a katydid under high background noise levels.

    PubMed

    Hartbauer, Manfred; Radspieler, Gerald; Römer, Heiner

    2010-09-01

    Katydid receivers face the problem of detecting behaviourally relevant predatory cues from echolocating bats in the same frequency domain as their own conspecific mating signals. We therefore tested the hypothesis that katydids are able to detect the presence of insectivorous bats in spike discharges at early stages of nervous processing in the auditory pathway by using the temporal details characteristic for responses to echolocation sequences. Spike activity was recorded from an identified nerve cell (omega neuron) under both laboratory and field conditions. In the laboratory, the preparation was stimulated with sequences of bat calls at different repetition rates typical for the guild of insectivorous bats, in the presence of background noise. The omega cell fired brief high-frequency bursts of action potentials in response to each bat sound pulse. Repetition rates of 18 and 24 Hz of these pulses resulted in a suppression of activity resulting from background noise, thus facilitating the detection of bat calls. The spike activity typical for responses to bat echolocation contrasts to responses to background noise, producing different distributions of inter-spike intervals. This allowed development of a 'neuronal bat detector' algorithm, optimized to detect responses to bats in afferent spike trains. The algorithm was applied to more than 24 hours of outdoor omega-recordings performed either at a rainforest clearing with high bat activity or in rainforest understory, where bat activity was low. In 95% of cases, the algorithm detected a bat reliably, even under high background noise, and correctly rejected responses when an electronic bat detector showed no response. PMID:20709932

  9. Efficacy of Endoscopically Created Bypass Anastomosis in Treatment of Afferent Limb Syndrome: A Single-Center Study.

    PubMed

    Rodrigues-Pinto, Eduardo; Grimm, Ian S; Baron, Todd H

    2016-04-01

    Afferent limb syndrome is a postoperative complication of gastrointestinal surgery, resulting from obstruction of a biliary-enteric limb. Surgery has been the cornerstone of treatment for this condition, but advances in endoscopic and percutaneous techniques could offer less-invasive options. Creation of an internal endoscopic anastomosis between the obstructed afferent limb and an adjacent gastrointestinal lumen can relieve symptoms and might provide a long-term solution. We report the efficacy of endoscopic treatment of afferent limb syndrome using lumen-apposing self-expandable metal stents to create 3 types of enteric anastomoses: a jejunojejunostomy, 2 gastrojejunostomies, and a duodenuojejunostomy in patients who developed afferent limb obstruction following a resection for pancreaticobiliary cancer. PMID:26674590

  10. Regulation of Piezo2 Mechanotransduction by Static Plasma Membrane Tension in Primary Afferent Neurons.

    PubMed

    Jia, Zhanfeng; Ikeda, Ryo; Ling, Jennifer; Viatchenko-Karpinski, Viacheslav; Gu, Jianguo G

    2016-04-22

    The Piezo2 channel is a newly identified mammalian mechanical transducer that confers rapidly adapting mechanically activated (RA-MA) currents in primary afferent neurons. The Piezo2 channels sense rapid membrane displacement, but it is not clear whether they are sensitive to osmotic swelling, which slowly increases static plasma membrane tension (SPMT). Here, we show that SPMT exerts a profound impact on the mechanical sensitivity of RA-MA channels in primary afferent neurons. RA-MA currents are greatly enhanced, and the mechanical threshold was reduced in both primary afferent neurons of rat dorsal root ganglia (DRG) and HEK293 cells heterologously expressing Piezo2 when these cells undergo osmotic swelling to increase SPMT. Osmotic swelling switches the kinetics of RA-MA currents to the slowly adapting type in both cultured DRG neurons and HEK293 cells heterologously expressing Piezo2. The potentiation of RA-MA currents is abolished when cultured DRG neurons are treated with cytochalasin D, an actin filament disruptor that prevents SPMT of cultured DRG neurons from an increase by osmotic swelling. Osmotic swelling significantly increases DRG neuron mechano-excitability such that a subthreshold mechanical stimulus can result in action potential firing. Behaviorally, the mechanical hind paw withdrawal threshold in rats is reduced following the injection of a hypotonic solution, but this osmotic effect is abolished when cytochalasin D or Gd(3+) is co-administered with the hypo-osmotic solution. Taken together, our findings suggest that Piezo2-mediated mechanotransduction is regulated by SPMT in primary afferent neurons. Because SPMT can be changed by multiple biological factors, our findings may have broad implications in mechanical sensitivity under physiological and pathological conditions. PMID:26929410

  11. The auriculo-vagal afferent pathway and its role in seizure suppression in rats

    PubMed Central

    2013-01-01

    Background The afferent projections from the auricular branch of the vagus nerve (ABVN) to the nucleus tractus solitaries (NTS) have been proposed as the anatomical basis for the increased parasympathetic tone seen in auriculo-vagal reflexes. As the afferent center of the vagus nerve, the NTS has been considered to play roles in the anticonvulsant effect of cervical vagus nerve stimulation (VNS). Here we proposed an “auriculo-vagal afferent pathway” (AVAP), by which transcutaneous auricular vagus nerve stimulation (ta-VNS) suppresses pentylenetetrazol (PTZ)-induced epileptic seizures by activating the NTS neurons in rats. Results The afferent projections from the ABVN to the NTS were firstly observed in rats. ta-VNS increased the first grand mal latency of the epileptic seizure and decreased the seizure scores in awake rats. Furthermore, when the firing rates of the NTS neurons decreased, epileptiform activity manifested as electroencephalogram (EEG) synchronization increased with 0.37±0.12 s delay in anaesthetized rats. The change of instantaneous frequency, mean frequency of the NTS neurons was negative correlated with the amplitude of the epileptic activity in EEG traces. ta-VNS significantly suppressed epileptiform activity in EEG traces via increasing the firing rates of the neurons of the NTS. In comparison with tan-VNS, the anticonvulsant durations of VNS and ta-VNS were significantly longer (P<0.01). There was no significant difference between the anticonvulsant durations of VNS and ta-VNS (P>0.05). The anticonvulsant effect of ta-VNS was weakened by reversible cold block of the NTS. Conclusions There existed an anatomical relationship between the ABVN and the NTS, which strongly supports the concept that ta-VNS has the potential for suppressing epileptiform activity via the AVAP in rats. ta-VNS will provide alternative treatments for neurological disorders, which can avoid the disadvantage of VNS. PMID:23927528

  12. Temperature Differentially Facilitates Spontaneous but Not Evoked Glutamate Release from Cranial Visceral Primary Afferents

    PubMed Central

    Fawley, Jessica A.; Hofmann, Mackenzie E.; Largent-Milnes, Tally M.; Andresen, Michael C.

    2015-01-01

    Temperature is fundamentally important to all biological functions including synaptic glutamate release. Vagal afferents from the solitary tract (ST) synapse on second order neurons in the nucleus of the solitary tract, and glutamate release at this first central synapse controls autonomic reflex function. Expression of the temperature-sensitive Transient Receptor Potential Vanilloid Type 1 receptor separates ST afferents into C-fibers (TRPV1+) and A-fibers (TRPV1-). Action potential-evoked glutamate release is similar between C- and A-fiber afferents, but TRPV1 expression facilitates a second form of synaptic glutamate release in C-fibers by promoting substantially more spontaneous glutamate release. The influence of temperature on different forms of glutamate release is not well understood. Here we tested how temperature impacts the generation of evoked and spontaneous release of glutamate and its relation to TRPV1 expression. In horizontal brainstem slices of rats, activation of ST primary afferents generated synchronous evoked glutamate release (ST-eEPSCs) at constant latency whose amplitude reflects the probability of evoked glutamate release. The frequency of spontaneous EPSCs in these same neurons measured the probability of spontaneous glutamate release. We measured both forms of glutamate from each neuron during ramp changes in bath temperature of 4–5°C. Spontaneous glutamate release from TRPV1+ closely tracked with these thermal changes indicating changes in the probability of spontaneous glutamate release. In the same neurons, temperature changed axon conduction registered as latency shifts but ST-eEPSC amplitudes were constant and independent of TRPV1 expression. These data indicate that TRPV1-operated glutamate release is independent of action potential-evoked glutamate release in the same neurons. Together, these support the hypothesis that evoked and spontaneous glutamate release originate from two pools of vesicles that are independently

  13. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    PubMed

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. PMID:25056352

  14. 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

  15. Effect of estrogen on vagal afferent projections to the brainstem in the female.

    PubMed

    Ciriello, John; Caverson, Monica M

    2016-04-01

    The effects of 17β-estradiol (E) on the distribution and density of brainstem projections of small or large diameter primary vagal afferents were investigated in Wistar rats using transganglionic transport of wheat germ agglutinin- (WGA; preferentially transported by non-myelinated afferent C-fibers; 2%), or cholera toxin B-subunit- (CTB, 5%; preferentially transported by large myelinated afferent A-fibers) conjugated horseradish peroxidase (HRP) in combination with the tetramethylbenzidine method in age matched ovariectomized (OVX) only or OVX and treated with E (OVX+E; 30 pg/ml plasma) females for 12 weeks. Additionally, these projections were compared to aged matched males. Unilateral microinjection of WGA-HRP into the nodose ganglion resulted in dense anterograde labeling bilaterally, with an ipsilateral predominance in several subnuclei of the nucleus of the solitary tract (NTS) and in area postrema that was greatest in OVX+E animals compared to OVX only and males. Moderately dense anterograde labeling was also observed in paratrigeminal nucleus (PAT) of the OVX+E animals. CTB-HRP produced less dense anterograde labeling in the NTS complex, but had a wider distribution within the brainstem including the area postrema, dorsal motor nucleus of the vagus, PAT, the nucleus ambiguus complex and ventrolateral medulla in all groups. The distribution of CTB-HRP anterograde labeling was densest in OVX+E, less dense in OVX only females and least dense in male rats. Little, if any, labeling was found within PAT in males using either WGA-or CTB-HRP. Taken together, these data suggest that small, non-myelinated (WGA-labeled) and large myelinated (CTB-labeled) diameter vagal afferents projecting to brainstem autonomic areas are differentially affected by circulating levels of estrogen. These effects of estrogen on connectivity may contribute to the sex differences observed in central autonomic mechanisms between gender, and in females with and without estrogen. PMID

  16. [Changes in the afferent activity of the vagus nerve and the rectal temperature in rats following Escherichia coli endotoxin administration].

    PubMed

    Lapsha, V I; Lukashenko, T M; Utkina, L N; Gurin, V N

    2001-10-01

    In anaesthetised rats, i.p. administration of the Echerichia coli lipopolysaccharide in doses 5 mcg/kg (LPS) increased afferent activity of the cervical vagus, whereas 100 and 1000 mcg/kg doses inhibited the afferent discharges. Pyrogen-free saline (PFS) did not alter the activity. Rectal temperature (RT) was decreased by the PFS and by large doses of the LPS. Sodium salicylate administration prevented the effects. PMID:11767451

  17. Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.