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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. Pupillary responses to chromatic stimulus

    NASA Astrophysics Data System (ADS)

    Suaste-Gomez, Ernesto; Rodriguez Guzman, M. C. Ma. Dolores A.; Druzgalski, Christopher

    2000-06-01

    Pupillary responses of the subjects under chromatic visual stimulation were filmed with video-oculography systems (VOG). Specifically, programmable chromatic visual stimuli were displayed on the monitor of a personal computer (PC) and responses tested in several normal subjects and those with ophthalmic pathologic conditions. Visual excitation utilized a reversal stimulus checkerboard pattern. Image processing techniques were applied in order to evaluate the pupil variations due to chromatic stimulation. In particular, the studies determined a relationship between pupillary response (PR) and steady-state retinal sensitivity (photopic vision). Finally, the retinal illuminance in trolands (td), as a product of the pupil area in mm2 and luminance in cd/m2 to full-field chromatic stimulation (FFCS) and checkerboard pattern reversal chromatic stimulation (CPRCS) was determined.

  3. Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

    PubMed Central

    Gracitelli, Carolina P. B.; Tatham, Andrew J.; Zangwill, Linda M.; Weinreb, Robert N.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Paranhos, Augusto; Baig, Saif; Medeiros, Felipe A.

    2016-01-01

    Purpose We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. Methods A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. Results There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R2 = 0.350, P < 0.001) and SAP MD (R2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. Conclusions Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma. PMID:27064394

  4. Cross-sectional pupillographic evaluation of relative afferent pupillary defect in age-related macular degeneration.

    PubMed

    Takayama, Kei; Ito, Yasuki; Kaneko, Hiroki; Nagasaka, Yosuke; Tsunekawa, Taichi; Sugita, Tadasu; Terasaki, Hiroko

    2016-09-01

    To evaluate, using pupillography, the difference between eyes affected by age-related macular degeneration and their contralateral normal eyes with regard to the mean relative afferent pupillary defect (RAPD) score. Also, to ascertain any correlations between this difference in RAPD score and differences in visual acuity or age-related macular degeneration (AMD) dimensions. Measurements were made using the RAPDx pupillographer (Konan Medical, Nishinomiya, Japan), which analyzes pupil response to light stimulation. Both best corrected visual acuity (converted to logMAR) and greatest linear dimension (GLD; calculated on the basis of fluorescence angiography images) were measured. The correlations between RAPD difference and logMAR difference, and GLD difference were then analyzed. The study included 32 patients (18 men, 14 women; mean age = 74.8 ± 9.7 years) who had AMD in 1 eye and a normal fundus in the contralateral eye. Mean resting pupil diameter, mean latency onset of constriction, mean velocity of constriction, and recovery were not significantly different in AMD eyes compared with normal eyes. The mean amplitude of constriction was smaller (P = 0.028), and the mean latency of maximum constriction was shorter (P = 0.0013) in AMD eyes than in normal eyes. Regarding RAPD scores, there was a significant correlation between visual acuity difference and RAPD score differences of both amplitude (P < 0.001, r = 0.53) and latency (P = 0.034, r = 0.33). GLD difference was also significantly correlated with differences in both amplitude (P = 0.021, r = 0.36) and latency (P = 0.033, r = 0.33) scores. RAPD outcomes were correlated with visual acuity and AMD dimension. Automated pupillography may be a useful tool in monitoring the progression of AMD and assessing changes in retinal function that result from novel interventions. PMID:27684848

  5. A linear chromatic mechanism drives the pupillary response.

    PubMed Central

    Tsujimura, S.; Wolffsohn, J. S.; Gilmartin, B.

    2001-01-01

    Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or nonlinear chromatic mechanism drives pupillary responses by using test stimuli of various colours that are defined in cone contrast space. The pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously objectively measured by photorefraction. The results with isochromatic and isoluminant stimuli showed that the accommodative level remained approximately constant (< 0.25 D change in mean level) even when the concurrent pupillary response was large (ca. 0.30 mm). The pupillary response to an isoluminant grating was sustained, delayed (by ca. 60 ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were used and isoresponse contours in cone contrast space were obtained. The results showed that the isoresponse contour in cone contrast space is well described (r(2) = 0.99) by a straight line with a positive slope. The results indicate that a /L - M/ linear chromatic mechanism, whereby a signal from the long wavelength cone is subtracted from that of the middle wavelength cone and vice versa, drives pupillary responses. PMID:11674867

  6. Pupillary responses evoked by electrical stimulation of area pretectalis in cats.

    PubMed

    Shoumura, K; Imai, H

    1986-01-01

    Pupillary responses evoked by electrical stimulation of the area pretectalis and neighboring midbrain structures were studied in the cat. The pupillary responses evoked were recorded using an infrared pupilloanalyzing system. Bilateral pupillary constriction was evoked with a low threshold current intensity by stimulation of the nucleus pretectalis medialis, nucleus pretectalis olivaris, rostral part of the nucleus pretectalis posterior, the most rostral part of the periaqueductal grey and the nucleus of posterior commissure. Bilateral pupillary dilation was induced with a low threshold current intensity by stimulating the nucleus pretectalis anterior, caudal periaqueductal grey and the midbrain tegmentum. The effects of changing stimulus intensity and stimulus frequency were also studied.

  7. Dynamic Visual Acuity Associated With Eye Movements And Pupillary Responses

    NASA Astrophysics Data System (ADS)

    Suaste, Ernesto; García, Nadia; Rodríguez, Dolores; Zúñiga, Arturo

    2004-09-01

    Objectively was evaluate dynamic visual acuity (DVA), using moving optotypes, while monitoring eye movements and pupillary responses. Under controlled conditions of luminance and contrast the viewers were asked to look carefully at a moving alphabetic letter. The letter was moved in the horizontal plane at a determined speed by a sinusoidal frequency generator. The initial frequency was gradually incremented until the viewer reported was not able to distinguish the object. Objective measures of DVA were obtained using video-oculography (VOG) in which, pupillary images and eye movements were analyzed by image processing. We found that when a large dilatation of the pupil is presented coincided with a pause eye movement (0.1s). It was when the viewer leaves to see clearly the letter of Snellen. The changes of pupil diameter of the five viewers were found averages to nasal trajectory from 3.58 mm (0 Hz) to 3.85 mm (1Hz), and to temporal trajectory from 3.54 mm (0 Hz) to 3.96 mm (1 Hz). Also, the bandwidth since 0.6 to 1.2 Hz, of the viewers due to the response at the stimulus (letter of Snellen) with 20° of amplitude, was obtained.

  8. 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

  9. 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

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

    PubMed

    Binda, Paola; Murray, Scott O

    2015-02-02

    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.

  11. 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.

  12. 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.

  13. The development of the pupillary light reflex and menace response in neonatal lambs and kids.

    PubMed

    Raoofi, Afshin; Mirfakhraie, Pejman; Yourdkhani, Sorush

    2011-03-01

    The aim of this study was to investigate the development of the pupillary light reflex and menace response in neonatal lambs and goat kids. Thirty lambs and 33 kids were assessed daily from birth until the pupillary light reflex and menace response had become established. All animals had a controlled pupillary light reflex within 20 h of birth. Lambs and kids had developed menace responses by 8 ± 3 and 14 ± 2 days, respectively. The Mann-Whitney test revealed a significant difference (P < 0.001) in the ages at which lambs and kids developed a menace response. Male kids developed this response significantly (P = 0.006) later than females. There was no sex difference in the menace response in the lambs. Overall, the findings indicated that lambs develop a menace response earlier than kids, and female kids develop this response more rapidly than their male counterparts.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. The Pupillary Response as an Index of Cognitive Processing in Mentally Retarded Persons. Final Report.

    ERIC Educational Resources Information Center

    Buckhalt, Joseph A.

    Two studies examined the effectiveness of pupillary measurements to indicate cognitive processes in educable mentally retarded (EMR) and nonretarded elementary and high school students. In the first study, pupillary scores from 20 nonretarded and 10 EMR students were measured for two conditions of an auditory task: listening and remembering.…

  1. 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.

  2. The musculature and pupillary response of the great horned owl iris.

    PubMed

    Oliphant, L W; Johnson, M R; Murphy, C; Howland, H

    1983-12-01

    There is considerable confusion in the literature regarding the nature of the musculature of the avian iris. The most commonly held view is that both the sphincter and dilator are striated. The iris of the Great Horned Owl (Bubo virginianus) has a complex iridial musculature consisting of three circumferential components (a myoepithelium, smooth muscle and striated muscle) and two radial components (a well-developed myoepithelium and a few striated fibers). On the basis of the anatomy and relative development of these components, and a quantitative analysis of the pupillary reflex, it is proposed that the circumferential striated muscle is the primary pupillary constrictor and radial myoepithelium is the primary dilator. The annular band of smooth muscle may play an important role in maintaining pupillary size. PMID:6662207

  3. 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

  4. 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.

  5. 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

  6. Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.

    PubMed

    Olausson, Håkan; Cole, Jonathan; Rylander, Karin; McGlone, Francis; Lamarre, Yves; Wallin, B Gunnar; Krämer, Heidrun; Wessberg, Johan; Elam, Mikael; Bushnell, M Catherine; Vallbo, Ake

    2008-01-01

    In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects' ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.

  7. 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

  8. 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

  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.

  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. 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

  13. Renal afferents responsive to chemical and mechanical pelvic stimuli in the rabbit.

    PubMed

    Genovesi, S; Pieruzzi, F; Camisasca, P; Golin, R; Zanchetti, A; Stella, A

    1997-05-01

    1. Afferent nerve fibres sensitive to changes in the renal chemical environment have been found in the rat. To verify the existence of these fibres in the rabbit and their response pattern, afferent renal nerve activity was recorded during pelvic perfusions with NaCl solutions at different concentrations. 2. The experiments were carried out in 13 anaesthetized rabbits. Arterial pressure from a femoral catheter and afferent renal nerve activity from the distal stump of a cut renal nerve bundle were recorded. Three catheters were inserted into the renal pelvis to measure pelvic pressure, to allow pelvic perfusions at constant rates and to drain pelvic fluids. 3. After a control period, the pelvis was perfused with physiological saline (0.14 mol/l for 2 min), followed by one of a series of solutions containing increasing concentrations of NaCl (0.5, 0.75, 1.0 and 1.5 mol/l for 2 min). Pelvic perfusion was performed both at a low (0.2 ml/min) and a high (0.8 ml/min) flow rate for each solution tested. 4. In all animals arterial pressure was not modified during pelvic perfusions. Physiological saline did not change afferent renal nerve activity at the low perfusion rate, but it significantly increased afferent renal nerve activity and pelvic pressure at the high rate. Hypertonic NaCl solutions caused progressive increases in afferent renal nerve activity at both perfusion rates, and these effects were larger at the high perfusion rate. 5. These data demonstrate, in the rabbit, the existence of renal afferent nerves sensitive to discrete changes in pelvic ionic or osmotic concentration. The neural response is enhanced when renal mechano- and chemo-receptors are simultaneously activated.

  14. Working memory load predicts visual search efficiency: Evidence from a novel pupillary response paradigm.

    PubMed

    Attar, Nada; Schneps, Matthew H; Pomplun, Marc

    2016-10-01

    An observer's pupil dilates and constricts in response to variables such as ambient and focal luminance, cognitive effort, the emotional stimulus content, and working memory load. The pupil's memory load response is of particular interest, as it might be used for estimating observers' memory load while they are performing a complex task, without adding an interruptive and confounding memory test to the protocol. One important task in which working memory's involvement is still being debated is visual search, and indeed a previous experiment by Porter, Troscianko, and Gilchrist (Quarterly Journal of Experimental Psychology, 60, 211-229, 2007) analyzed observers' pupil sizes during search to study this issue. These authors found that pupil size increased over the course of the search, and they attributed this finding to accumulating working memory load. However, since the pupil response is slow and does not depend on memory load alone, this conclusion is rather speculative. In the present study, we estimated working memory load in visual search during the presentation of intermittent fixation screens, thought to induce a low, stable level of arousal and cognitive effort. Using standard visual search and control tasks, we showed that this paradigm reduces the influence of non-memory-related factors on pupil size. Furthermore, we found an early increase in working memory load to be associated with more efficient search, indicating a significant role of working memory in the search process.

  15. Pupillary signs in diabetic autonomic neuropathy.

    PubMed Central

    Smith, S E; Smith, S A; Brown, P M; Fox, C; Sönksen, P H

    1978-01-01

    Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex responses to light flashes of an intensity adjusted for individual retinal sensitivities. The pupillary findings were compared with results of five tests of cardiovascular function and five tests of peripheral sensory and motor nerve function. Almost all the patients with autonomic neuropathy had pupillary signs, which we therefore conclude are a common manifestation of diabetic autonomic neuropathy. PMID:709128

  16. Histamine (H3) receptors modulate the excitatory amino acid receptor response of the vestibular afferents.

    PubMed

    Chávez, Hortencia; Vega, Rosario; Soto, Enrique

    2005-12-01

    Although the effectiveness of histamine-related drugs in the treatment of peripheral and central vestibular disorders may be explained by their action on the vestibular nuclei, it has also been shown that antivertigo effects can take place at the peripheral level. In this work, we examined the actions of H3 histaminergic agonists and antagonists on the afferent neuron electrical discharge in the isolated inner ear of the axolotl. Our results indicate that H3 antagonists such as thioperamide, clobenpropit, and betahistine (BH) decreased the electrical discharge of afferent neurons by interfering with the postsynaptic response to excitatory amino acid agonists. These results lend further support to the idea that the antivertigo action of histamine-related drugs may be caused, at least in part, by a decrease in the sensory input from the vestibular endorgans. The present data show that the inhibitory action of the afferent neurons discharge previously described for BH is not restricted to this molecule but is also shared by other H3 antagonists.

  17. 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

  18. 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.

  19. 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

  20. Action of vibration on the response of cat muscle spindle Ia afferents to low frequency sinusoidal stretching.

    PubMed Central

    Matthews, P B; Watson, J D

    1981-01-01

    1. A study has been made of the effect of continuous vibration, at 150 Hz, upon the response of muscle spindle afferents to low frequency sinusoidal stretching (1 and 8 Hz). Using the soleus muscle of the anaesthetized cat, with severed ventral roots, recordings were made of single Ia afferents and of the massed Ia afferent discharges in the main bulk of the cut L7 dorsal root. 2. When the amplitude of vibration was large (50 micrometers, short pulses) and that of the sinusoidal stretching was not too great (50-100 micrometers, peak-to-peak) the discharge of the afferents was largely locked 1:1 to the vibration and the response to the sinusoidal stretching was abolished. 3. When the amplitude of the vibration was reduced to below that eliciting continuous afferent driving, then the response to sinusoidal stretching of any amplitude was often markedly increased. This arose through the vibration having a much more powerful excitatory action during the rising phase of the sinusoidal stretch than it did during the falling phase. 4. Averaged over a full cycle, the phase of the response to the sinusoidal stretching tended to be delayed during the vibration in comparison with the normal. This was largely dependent upon the afferents continuing to respond maximally to the vibration around the peak of the sinusoidal stretch, at which stage their unvibrated response is declining, rather than to a phase lag of the whole pattern of response. 5. The results are discussed in relation to the effects of vibration on tremor and the human stretch reflex, and on the determination of the frequency-response of spindle afferents. PMID:6458696

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Chewing-induced hypertension in afferent baroreflex failure: A sympathetic response?

    PubMed Central

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

    2016-01-01

    Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure due to baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD, and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and RR intervals were measured continuously while chewing gum (n= 15), swallowing food (n=20) and distending the stomach with a gastrostomy feed (n=9). Responses were compared to those of normal controls (n=10) and of patients with autonomic failure (n=10) who have chronically impaired sympathetic outflow. In patients with FD, swallowing food was associated with a marked, but transient pressor response (p<0.0001) and additional signs of sympathetic activation including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in controls (p=0.0001), but was absent in patients with autonomic failure. In patients with FD distending the stomach with a gastrostomy feed failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure that is exaggerated in patients with FD due to blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD. PMID:26435473

  7. Neural responses from the filiform receptor neuron afferents of the wind-sensitive cercal system in three cockroach species.

    PubMed

    Olsen, Anne C K; Triblehorn, Jeffrey D

    2014-09-01

    The wind-sensitive insect cercal system is involved in many important behaviors, such as initiating terrestrial escape responses and providing sensory feedback during flight. The occurrence of these behaviors vary in cockroach species Periplaneta americana (strong terrestrial response and flight), Blaberus craniifer (weak terrestrial response and flight), and Gromphodorhina portentosa (no terrestrial response and no flight). A previous study focusing on wind-sensitive interneuron (WSI) responses demonstrated that variations in sensory processing of wind information accompany these behavioral differences. In this study, we recorded extracellularly from the cercal nerve to characterize filiform afferent population responses to different wind velocities to investigate how sensory processing differs across these species at the initial encoding of wind. We compared these results and responses from the WSI population to examine information transfer at the first synapse. Our main results were: (1) G. portentosa had the weakest responses of the three species over the stimulus duration and possessed the smallest cerci with the least filiform hair receptors of the three species; (2) B. craniifer filiform responses were similar to or greater than P. americana responses even though B. craniifer possessed smaller cerci with less filiform hair receptors than P. americana; (3) the greater filiform afferent responses in B. craniifer, including a larger amplitude second positive peak compared to the other two species, suggest more synchronous activity between filiform afferents in this species; (4) the transfer of information at the first synapse appears to be similar in both P. americana and G. portentosa, but different in B. craniifer.

  8. Neural responses from the filiform receptor neuron afferents of the wind-sensitive cercal system in three cockroach species

    PubMed Central

    Olsen, Anne C.K.; Triblehorn, Jeffrey D.

    2014-01-01

    The wind-sensitive insect cercal system is involved in many important behaviors, such as initiating terrestrial escape responses and providing sensory feedback during flight. The occurrence of these behaviors vary in cockroach species Periplaneta americana (strong terrestrial response and flight), Blaberus craniifer (weak terrestrial response and flight), and Gromphodorhina portentosa (no terrestrial response and no flight). A previous study focusing on wind-sensitive interneuron (WSI) responses demonstrated that variations in sensory processing of wind information accompany these behavioral differences. In this study, we recorded extracellurlarly from the cercal nerve to characterize filiform afferent population responses to different wind velocities to investigate how sensory processing differs across these species at the initial encoding of wind. We compared these results and responses from the WSI population to examine information transfer at the first synapse. Our main results were: 1) G portentosa had the weakest responses of the three species over the stimulus duration and possessed the smallest cerci with the least filiform hair receptors of the three species; 2) B. craniifer filiform responses were similar to or greater than P. americana responses even though B. craniifer possessed smaller cerci with less filiform hair receptors than P. americana; 3) the greater filiform afferent responses in B. craniifer, including a larger amplitude second positive peak compared to the other two species, suggest more synchronous activity between filiform afferents in this species; 4) the transfer of information at the first synapse appears to be similar in both P. americana and G. portentosa, but different in B. craniifer. PMID:25046275

  9. 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.

  10. Variation in response dynamics of regular and irregular vestibular-nerve afferents during sinusoidal head rotations and currents in the chinchilla.

    PubMed

    Kim, Kyu-Sung; Minor, Lloyd B; Della Santina, Charles C; Lasker, David M

    2011-05-01

    In mammals, vestibular-nerve afferents that innervate only type I hair cells (calyx-only afferents) respond nearly in phase with head acceleration for high-frequency motion, whereas afferents that innervate both type I and type II (dimorphic) or only type II (bouton-only) hair cells respond more in phase with head velocity. Afferents that exhibit irregular background discharge rates have a larger phase lead re-head velocity than those that fire more regularly. The goal of this study was to investigate the cause of the variation in phase lead between regular and irregular afferents at high-frequency head rotations. Under the assumption that externally applied galvanic currents act directly on the nerve, we derived a transfer function describing the dynamics of a semicircular canal and its hair cells through comparison of responses to sinusoidally modulated head velocity and currents. Responses of all afferents were fit well with a transfer function with one zero (lead term). Best-fit lead terms describing responses to current for each group of afferents were similar to the lead term describing responses to head velocity for regular afferents (0.006 s + 1). This finding indicated that the pre-synaptic and synaptic inputs to regular afferents were likely to be pure velocity transducers. However, the variation in phase lead between regular and irregular afferents could not be explained solely by the ratio of type I to II hair cells (Baird et al 1988), suggesting that the variation was caused by a combination of pre- (type of hair cell) and post-synaptic properties.

  11. 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.

  12. Relation between discharge regularity and responses to externally applied galvanic currents in vestibular nerve afferents of the squirrel monkey.

    PubMed

    Goldberg, J M; Smith, C E; Fernández, C

    1984-06-01

    Most vestibular nerve afferents can be classified as regularly or irregularly discharging. Two factors are theoretically identified as being potentially responsible for differences in discharge regularity. The first, ascribable to synaptic noise, is the variance (sigma v2) characterizing the transmembrane voltage fluctuations of the axon's spike trigger site, i.e., the place where impulses normally arise. The second factor is the slope (dmuv/dt) of the trigger site's postspike recovery function. Were (dmuv/dt) a major determinant of discharge regularity, the theory predicts that the more irregular the discharge of a unit, the greater should be its sensitivity to externally applied galvanic currents and the faster should be the postspike recovery of its electrical excitability. The predictions would not hold if differences in the discharge regularity between units largely reflected variations in sigma v. To test these predictions, the responses of vestibular nerve afferents to externally applied galvanic currents were studied in the barbiturate-anesthetized squirrel monkey. Current steps of 5-s duration and short (50 microsecond) shocks were delivered by way of the perilymphatic space of the vestibule. Results were similar regardless of which end organ an afferent innervated. The regularity of discharge of each unit was expressed by a normalized coefficient of variation (CV*). The galvanic sensitivity (beta p) of a unit, measured from its response to current steps, was linearly related to discharge regularity (CV*), there being approximately 20-fold variations in both variables across the afferent population. Various geometric factors--including fiber diameter, position of individual axons within the various nerve branches, and the configuration of unmyelinated processes within the sensory epithelium--are unlikely to have made a major contribution to the positive relation between beta P and CV*. The postspike recovery of electrical excitability was measured as

  13. Analysis of afferent responses from isolated semicircular canal of the guitarfish using rotational acceleration white-noise inputs. I. Correlation of response dynamics with receptor innervation.

    PubMed

    O'Leary, D P; Dunn, R F

    1976-05-01

    The small-signal linear characteristics of afferent responses from the isolated semicircular canal were described by the use of white-noise rotational acceleration inputs. The results, based on cross-correlation analysis, showed a striking and systematic variation in linear system impulse response characteristics from afferents which innervated different regions of the receptor. Afferents from centrally located nerve bundles innervating the crest region of the crista exhibited an initial maximum response amplitude followed by a rapid decay. In contrast, afferents from extreme rostral and caudal nerve bundles innervating the crista slopes exhibited an initial rise up to a low-amplitude maximum followed by a slower decay. These results imply that the afferents innervating a single canal do not merely carry redundant information concerning current head acceleration, but could be considered an ensemble of specific classes of filters that are tuned individually to specific classes of head movements. On the basis of these considerations, a new hypothesis of matched filter detection was proposed as relevant to information processing and dynamic control in central vestibular pathways. PMID:948010

  14. Coronary responses to cold air inhalation following afferent and efferent blockade

    PubMed Central

    Gao, Zhaohui; McQuillan, Patrick M.; Leuenberger, Urs A.; Sinoway, Lawrence I.

    2014-01-01

    Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (−15 to −30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise. PMID:24816257

  15. 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

  16. Effects of altered afferent articular input on sensation, proprioception, muscle tone and sympathetic reflex responses.

    PubMed

    Slosberg, M

    1988-10-01

    The influence of afferent articular and periarticular input on muscle tone, joint mobility, proprioception and pain is of considerable interest to practitioners using manipulation. It has long been hypothesized that dysfunctional articulations may generate altered patterns of afferent input. This article reviews the relevant studies that have investigated the impact of articular input on efferent activity under normal conditions and under conditions of altered joint function. The findings suggest that sensory input does have a substantial effect on efferent function and sensation. Furthermore, the studies indicate that the pattern of articular input may be significantly modified by joint inflammation, trauma and effusion and result in changes of muscle tone, joint mobility, proprioception and pain. PMID:3069947

  17. Cognitive context detection using pupillary measurements

    NASA Astrophysics Data System (ADS)

    Mannaru, Pujitha; Balasingam, Balakumar; Pattipati, Krishna; Sibley, Ciara; Coyne, Joseph

    2016-05-01

    In this paper, we demonstrate the use of pupillary measurements as indices of cognitive workload. We analyze the pupillary data of twenty individuals engaged in a simulated Unmanned Aerial System (UAS) operation in order to understand and characterize the behavior of pupil dilation under varying task load (i.e., workload) levels. We present three metrics that can be employed as real-time indices of cognitive workload. In addition, we develop a predictive system utilizing the pupillary metrics to demonstrate cognitive context detection within simulated supervisory control of UAS. Further, we use pupillary data collected concurrently from the left and right eye and present comparative results of the use of separate vs. combined pupillary data for detecting cognitive context.

  18. Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish.

    PubMed

    Haehnel-Taguchi, Melanie; Akanyeti, Otar; Liao, James C

    2014-09-15

    The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 μm/ms. However, spike rate did not change when the cupula was deflected below 8 μm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior.

  19. Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish

    PubMed Central

    Haehnel-Taguchi, Melanie; Akanyeti, Otar

    2014-01-01

    The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 μm/ms. However, spike rate did not change when the cupula was deflected below 8 μm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior. PMID:24966296

  20. The dependence of the response of cat spindle Ia afferents to sinusoidal stretch on the velocity of concomitant movement.

    PubMed Central

    Baumann, T K; Hulliger, M

    1991-01-01

    1. The responses of de-efferented soleus muscle spindle primary afferents to 1 Hz sinusoidal stretches, which were superimposed on triangular background movements of intermediate amplitude (1.2 mm, half peak-to-peak) and widely varying speed, were recorded in anaesthetized cats. 2. Compared with control responses to the same sinusoids applied at fixed mean muscle length, the sensitivity to small (50 and 100 microns, half peak-to-peak), but not to large (1000 microns), sinusoidal movements was dramatically reduced during concomitant stretching, unless the background movements were extremely slow (well below 0.005 resting lengths per second). 3. For small stretches (50 and 100 microns) the reduction of sensitivity caused by background movement depended on the speed of this movement. For the highest velocity studied (1.6 mm s-1, corresponding to about 0.03 resting lengths per second) sensitivity dropped to below 10% of the control values. 4. The functional implication is that the sensitivity of spindle Ia afferents to small irregularities of voluntary movements (of any but the slowest speeds) may well be very much lower than it has hitherto been inferred from the striking sensitivity to minute disturbances at fixed mean muscle length. The present finding clearly puts extra demands on the gain of any spinal or central reflex actions of the sensory feedback from spindle afferents. 5. The effect is interpreted in terms of the widely accepted cross-bridge hypothesis of spindle small-movement sensitivity. The result suggests that in de-efferented intrafusal muscle fibres, which are subjected to imposed stretches, connected cross-bridges (conveying a friction-like property to the contractile fibre poles) may exist not only in a state of permanent attachment, but also in a dynamic equilibrium between stretch-induced detachment and reattachment. Indirect evidence further suggests that the duration of this disruption and reattachment cycle is of the order of 1 s. PMID:1832716

  1. Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists.

    PubMed

    Lin, Yu-Jung; Lin, You Shuei; Lai, Ching Jung; Yuan, Zung Fan; Ruan, Ting; Kou, Yu Ru

    2013-02-01

    The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,β-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

  2. 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

  3. 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

  4. Test of the mechanotactile hypothesis: neuromast morphology and response dynamics of mechanosensory lateral line primary afferents in the stingray.

    PubMed

    Maruska, Karen P; Tricas, Timothy C

    2004-09-01

    The mechanotactile hypothesis proposes that ventral non-pored lateral line canals in the stingray function to facilitate localization of prey that contact the skin during benthic feeding. This study used comparative neurophysiological and morphological techniques to test whether ventral non-pored canals encode the velocity of skin movements, and show other adaptations that may enhance detection of tactile stimuli from their prey. Resting discharge rate of lateral line primary afferent neurons was lower among units from ventral than dorsal canal groups. The ventral non-pored canals had a higher proportion of silent units (31%) than either ventral (3%) or dorsal (13%) pored canals, thus may have an enhanced potential for detection of phasic contact with prey. Primary afferents from pored canals showed response characteristics consistent with acceleration detectors, with best frequencies of 20-30 Hz. In contrast, units from non-pored canals responded to tactile skin depression velocities of 30-630 microm s(-1) from 1-20 Hz, and encoded the velocity of canal fluid induced by skin movement with best frequencies of < or =10 Hz. Sensitivity of non-pored canals to direct skin depression velocity was 2-10 times greater than to hydrodynamic dipole stimulation near the skin. No morphological specialization of hair cell orientation was found among pored and non-pored canals. These low frequency, tactile response properties support the hypothesis that the stingray's non-pored ventral lateral line functions as a mechanotactile receptor subsystem used to guide small benthic invertebrates to the ventrally positioned mouth. PMID:15339942

  5. Response of hip joint afferent fibers to pressure and vibration in the cat.

    PubMed

    Aloisi, A M; Carli, G; Rossi, A

    1988-07-19

    Mechanical properties of 33 slowly adapting and 8 quickly adapting capsule receptors of the hip joint were investigated. All the slowly adapting receptors identified were of a limited range, discharging only when the femur was rotated to its limit of movement. They behaved as single-spot high-threshold pressure receptors as shown by the von Frey's hairs. In addition they showed a low sensitivity to vibratory stimuli applied perpendicularly to their receptive field. Only 14 out of 33 units were found to discharge following vibration; 11 could be driven 1:1 at different frequencies. There was a general trend to be entrained at lower amplitudes for higher frequencies of vibration. A positive correlation between the pressure threshold and both activation angle and vibration threshold was found. The mechanical properties of all the quickly adapting capsule receptors were found to be similar to those described in other tissues. Finally, unlike joint receptors, slowly adapting muscle afferents travelling in the same hip articular nerve were highly sensitive to pressure and vibratory stimuli.

  6. 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

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

    PubMed

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

    2015-04-15

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

  8. 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

  9. 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

  10. 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.

  11. Cardiovascular effects of afferent renal nerve stimulation.

    PubMed

    Stella, A; Weaver, L; Golin, R; Genovesi, S; Zanchetti, A

    1987-01-01

    Electrical stimulation of afferent renal nerves elicits an increase in arterial pressure and heart rate. The hypertensive response is presumably due to the widespread activation of the sympathetic nervous system leading to peripheral vasoconstriction. Interestingly, the kidney does not appear involved in this reflex excitatory response to afferent renal nerve stimulation since changes in vascular conductances and excretory functions are equal in both the innervated and denervated kidney, and secondary to changes in renal perfusion pressure. In addition, no changes in renin release from either kidneys are observed during afferent renal nerve stimulation. It is likely that the electrical stimulation of afferent renal nerves activates other reflexes exerting an inhibitory influence on efferent renal nerve activity. Indeed, neural renorenal reflexes which tonically inhibit renal functions have clearly been demonstrated. Furthermore, preferential inhibition of efferent renal nerve activity by cardiopulmonary and sinoaortic receptors has recently been shown during activation of other visceral afferents.

  12. 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

  13. Task-dependent changes in the responses to low-threshold cutaneous afferent volleys in the human lower limb.

    PubMed

    Burke, D; Dickson, H G; Skuse, N F

    1991-01-01

    1. In seven human subjects who were standing without support the sural nerves were stimulated electrically using trains of non-painful stimuli (five pulses at 300 Hz), designed to activate afferents from cutaneous mechanoreceptors. The reflex effects of the stimulus train on different muscles of the ipsilateral and contralateral legs were sought in post-stimulus averages of rectified EMG. Changes in the pattern of reflex influence were investigated when the subjects maintained different postures. 2. Clear reflex responses were seen in ipsilateral tibialis anterior, soleus, biceps femoris and vastus lateralis, but only when the muscles were actively contracting. In each muscle, inhibition was the dominant reflex response within the first 100 ms. In four of the seven subjects, reflex changes were detectable in the contralateral tibialis anterior and soleus, the peak-to-peak modulation within the first 200 ms being 25-50% of that for the homologous ipsilateral muscle. 3. When subjects attempted to stand on a tilted platform, an unstable platform or on one leg with the other flexed, different combinations of muscles were active, involving both flexors and extensors or predominantly flexors or predominantly extensors. In each posture the reflex effects were demonstrable only in the active muscles. 4. With ipsilateral tibialis anterior, there were task-dependent changes in the short-latency components of the EMG response, approximately 60 ms and 80 ms after the stimulus. When seated performing voluntary contractions these components were difficult to define, and when standing on a platform tilted toe-up they were small. When the ipsilateral leg was flexed or when standing on an unstable base, these early components were more prominent in each subject. With contralateral tibialis anterior, the dominant reflex pattern was inhibition when seated and contracting voluntarily, and facilitation during bipedal stance tilted toe-up. These changes in reflex pattern could not be

  14. 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.

  15. 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

  16. 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

  17. Pupillary contagion: central mechanisms engaged in sadness processing

    PubMed Central

    Harrison, Neil A.; Singer, Tania; Rotshtein, Pia; Dolan, Ray J.; Critchley, Hugo D.

    2006-01-01

    Empathic responses underlie our ability to share emotions and sensations with others. We investigated whether observed pupil size modulates our perception of other's emotional expressions and examined the central mechanisms modulated by incidental perception of pupil size in emotional facial expressions. We show that diminishing pupil size enhances ratings of emotional intensity and valence for sad, but not happy, angry or neutral facial expressions. This effect was associated with modulation of neural activity within cortical and subcortical regions implicated in social cognition. In an identical context, we show that the observed pupil size was mirrored by the observers’ own pupil size. This empathetic contagion engaged the brainstem pupillary control nuclei (Edinger–Westphal) in proportion to individual subject's sensitivity to this effect. These findings provide evidence that perception–action mechanisms extend to non-volitional operations of the autonomic nervous system. PMID:17186063

  18. 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

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

    PubMed Central

    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

  20. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity

    PubMed Central

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity. PMID:27694818

  1. Relationship between Human Pupillary Light Reflex and Circadian System Status.

    PubMed

    Bonmati-Carrion, Maria Angeles; Hild, Konstanze; Isherwood, Cheryl; Sweeney, Stephen J; Revell, Victoria L; Skene, Debra J; Rol, Maria Angeles; Madrid, Juan Antonio

    2016-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex (PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of the circadian system. Thus, evaluating PLR under short wavelength light (λmax ≤ 500 nm) and creating an integrated PLR parameter, as a possible tool to indirectly assess the status of the circadian system, becomes of interest. Nine monochromatic, photon-matched light stimuli (300 s), in 10 nm increments from λmax 420 to 500 nm were administered to 15 healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (Horne-Östberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations between the different PLR parameters and circadian status index obtained from WT, WA and L recordings and scores from questionnaires were calculated. In summary, we found markers of robust circadian rhythms, namely high stability, reduced fragmentation, high amplitude, phase advance and low internal desynchronization, were correlated with a reduced PLR to 460-490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR) parameters are proposed, that also showed an inverse correlation. These results demonstrate, for the first time, the existence of a close relationship between the circadian system robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC input. PMID:27636197

  2. Relationship between Human Pupillary Light Reflex and Circadian System Status

    PubMed Central

    Bonmati-Carrion, Maria Angeles; Hild, Konstanze; Isherwood, Cheryl; Sweeney, Stephen J.; Revell, Victoria L.; Skene, Debra J.; Rol, Maria Angeles; Madrid, Juan Antonio

    2016-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex (PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of the circadian system. Thus, evaluating PLR under short wavelength light (λmax ≤ 500 nm) and creating an integrated PLR parameter, as a possible tool to indirectly assess the status of the circadian system, becomes of interest. Nine monochromatic, photon-matched light stimuli (300 s), in 10 nm increments from λmax 420 to 500 nm were administered to 15 healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (Horne-Östberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations between the different PLR parameters and circadian status index obtained from WT, WA and L recordings and scores from questionnaires were calculated. In summary, we found markers of robust circadian rhythms, namely high stability, reduced fragmentation, high amplitude, phase advance and low internal desynchronization, were correlated with a reduced PLR to 460–490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR) parameters are proposed, that also showed an inverse correlation. These results demonstrate, for the first time, the existence of a close relationship between the circadian system robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC input. PMID:27636197

  3. 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

  4. Cognitive modulation of midbrain function: task-induced reduction of the pupillary light reflex.

    PubMed

    Steinhauer, S R; Condray, R; Kasparek, A

    2000-12-01

    The activation of processing resources has widespread effects in the nervous system. A model of pupillary control systems (Steinhauer S.R. , Hakerem G., 1992. The pupillary response in cognitive psychophysiology and schizophrenia. Ann. N.Y. Acad. Sci. 658, 182-204) had predicted that ongoing cognitive activation should result in inhibition of the light reaction at the level of the oculomotor nucleus, n. III, in the midbrain. In this study, modification of parameters of the pupillary reaction to light were examined during varying task demands. The averaged light reaction was recorded from 33 male and female healthy volunteers during the performance of a serial 7 subtraction task and compared to a 'no task' condition. For 13 subjects, an additional verbalization task with little processing demand (add 1) also was presented. Two types of effects were observed. Firstly, the tonic pupil diameter increased from the no task to the easy (add 1) task, and increased further in the more demanding condition (subtract 7). Secondly, the extent of the phasic light reaction was significantly reduced and the latency at the end of the contraction was significantly decreased in the 'subtract 7' condition compared to both the no task and easy conditions (which did not differ from each other). The locus of interference with the light reaction was the Edinger-Westphal complex of the oculomotor nucleus, which is the motor center for the pupillary sphincter muscles. Descending cortical influences inhibited the activity of the Edinger-Westphal complex. Thus, increasing activation had a tonic inhibitory effect on this center, while higher levels of processing complexity produced a separate component of inhibition that interacted with dynamic activation at this midbrain site. It was suggested that the variation in the light reaction is quantitatively responsive to varying processing loads, and may be utilized as a sensitive metric for a wide variety of cognitive operations.

  5. 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

  6. 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

  7. Short-latency afferent inhibition determined by the sensory afferent volley.

    PubMed

    Bailey, Aaron Z; Asmussen, Michael J; Nelson, Aimee J

    2016-08-01

    Short-latency afferent inhibition (SAI) is characterized by the suppression of the transcranial magnetic stimulation motor evoked potential (MEP) by the cortical arrival of a somatosensory afferent volley. It remains unknown whether the magnitude of SAI reflects changes in the sensory afferent volley, similar to that observed for somatosensory evoked potentials (SEPs). The present study investigated stimulus-response relationships between sensory nerve action potentials (SNAPs), SAI, and SEPs and their interrelatedness. Experiment 1 (n = 23, age 23 ± 1.5 yr) investigated the stimulus-response profile for SEPs and SAI in the flexor carpi radialis muscle after stimulation of the mixed median nerve at the wrist using ∼25%, 50%, 75%, and 100% of the maximum SNAP and at 1.2× and 2.4× motor threshold (the latter equated to 100% of the maximum SNAP). Experiment 2 (n = 20, age 23.1 ± 2 yr) probed SEPs and SAI stimulus-response relationships after stimulation of the cutaneous digital nerve at ∼25%, 50%, 75%, and 100% of the maximum SNAP recorded at the elbow. Results indicate that, for both nerve types, SAI magnitude is dependent on the volume of the sensory afferent volley and ceases to increase once all afferent fibers within the nerve are recruited. Furthermore, for both nerve types, the magnitudes of SAI and SEPs are related such that an increase in excitation within somatosensory cortex is associated with an increase in the magnitude of afferent-induced MEP inhibition. PMID:27226451

  8. 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.

  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. Detection thresholds of macaque otolith afferents.

    PubMed

    Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

    2012-06-13

    The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

  11. 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

  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. Primary afferent depolarization and frequency processing in auditory afferents.

    PubMed

    Baden, Tom; Hedwig, Berthold

    2010-11-01

    Presynaptic inhibition is a widespread mechanism modulating the efficiency of synaptic transmission and in sensory pathways is coupled to primary afferent depolarizations. Axonal terminals of bush-cricket auditory afferents received 2-5 mV graded depolarizing inputs, which reduced the amplitude of invading spikes and indicated presynaptic inhibition. These inputs were linked to a picrotoxin-sensitive increase of Ca(2+) in the terminals. Electrophysiological recordings and optical imaging showed that in individual afferents the sound frequency tuning based on spike rates was different from the tuning of the graded primary afferent depolarizations. The auditory neuropil of the bush-cricket Mecopoda elongata is tonotopically organized, with low frequencies represented anteriorly and high frequencies represented posteriorly. In contrast graded depolarizing inputs were tuned to high-frequencies anteriorly and to low-frequencies posteriorly. Furthermore anterior and posterior axonal branches of individual afferents received different levels of primary afferent depolarization depending on sound frequency. The presence of primary afferent depolarization in the afferent terminals indicates that presynaptic inhibition may shape the synaptic transmission of frequency-specific activity to auditory interneurons.

  14. 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.

  15. 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

  16. 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

  17. 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

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

    PubMed

    Feng, Bin; Brumovsky, Pablo R; Gebhart, Gerald F

    2010-03-01

    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.

  19. Force-sensitive afferents recruited during stance encode sensory depression in the contralateral swinging limb during locomotion.

    PubMed

    Hochman, Shawn; Hayes, Heather Brant; Speigel, Iris; Chang, Young-Hui

    2013-03-01

    Afferent feedback alters muscle activity during locomotion and must be tightly controlled. As primary afferent depolarization-induced presynaptic inhibition (PAD-PSI) regulates afferent signaling, we investigated hindlimb PAD-PSI during locomotion in an in vitro rat spinal cord-hindlimb preparation. We compared the relation of PAD-PSI, measured as dorsal root potentials (DRPs), to observed ipsilateral and contralateral limb endpoint forces. Afferents activated during stance-phase force strongly and proportionately influenced DRP magnitude in the swinging limb. Responses increased with locomotor frequency. Electrical stimulation of contralateral afferents also preferentially evoked DRPs in the opposite limb during swing (flexion). Nerve lesioning, in conjunction with kinematic results, support a prominent contribution from toe Golgi tendon organ afferents. Thus, force-dependent afferent feedback during stance binds interlimb sensorimotor state to a proportional PAD-PSI in the swinging limb, presumably to optimize interlimb coordination. These results complement known actions of ipsilateral afferents on PAD-PSI during locomotion.

  20. Development, plasticity and modulation of visceral afferents

    PubMed Central

    Christianson, Julie A.; Bielefeldt, Klaus; Altier, Christophe; Cenac, Nicolas; Davis, Brian M.; Gebhart, Gerald F.; High, Karin W.; Kollarik, Marian; Randich, Alan; Undem, Brad; Vergnolle, Nathalie

    2010-01-01

    Visceral pain is the most common reason for doctor visits in the US. Like somatic pain, virtually all visceral pain sensations begin with the activation of primary sensory neurons innervating the viscera and/or the blood vessels associated with these structures. Visceral afferents also play a central role in tissue homeostasis. Recent studies show that in addition to monitoring the state of the viscera, they perform efferent functions through the release of small molecules (e.g. peptides like CGRP) that can drive inflammation, thereby contributing to the development of visceral pathologies (e.g. diabetes Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M., 2006. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes, Cell 127 1123–1135). Visceral afferents are heterogeneous with respect to their anatomy, neurochemistry and function. They are also highly plastic in that their cellular environment continuously influences their response properties. This plasticity makes them susceptible to long-term changes that may contribute significantly to the development of persistent pain states such as those associated with irritable bowel syndrome, pancreatitis, and visceral cancers. This review examines recent insights into visceral afferent anatomy and neurochemistry and how neonatal insults can affect the function of these neurons in the adult. New approaches to the treatment of visceral pain, which focus on primary afferents, will also be discussed. PMID:19150371

  1. 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

  2. Mast cells drive mesenteric afferent signalling during acute intestinal ischaemia

    PubMed Central

    Jiang, Wen; Kirkup, Anthony J; Grundy, David

    2011-01-01

    Abstract Acute intestinal ischaemia stimulates visceral afferent nerves but the mechanisms responsible for this excitation are not fully understood. Mast cells may participate in this process as they are known to signal to mesenteric afferents during intestinal anaphylaxis and contribute to early inflammation and neuronal damage in response to cerebral ischaemia. We therefore hypothesised that mast cells are early responders to acute intestinal ischaemia and their activation initiates rapid signalling to the CNS via the excitation of mesenteric afferents. Primary afferent firing was recorded from a mesenteric nerve bundle supplying a segment of jejunum in anaesthetized adult rats. Acute focal ischaemia was produced by clamping the mesenteric vessels for 8 min, and reperfusion followed removal of the vessel clip. Two episodes of ischaemia–reperfusion (I–R) separated by a 30 min interval were performed. Drugs or their vehicles were administered 10 min before the 2nd I–R episode. Ischaemia caused a reproducible, intense and biphasic afferent firing that was temporally dissociated from the concomitantly triggered complex pattern of intestinal motor activity. The L-type calcium channel blocker, nifedipine, significantly attenuated this afferent firing by a mechanism independent of its action on intestinal tone. Ischaemia-induced afferent firing was also abrogated by the mast cell stabilizer, doxantrazole, and the H1 histamine receptor antagonist, pyrilamine. In contrast, the nicotinic receptor antagonist, hexamethonium, and the N-type calcium channel toxin, ω-conotoxin GVIA, each reduced the ischaemia-evoked motor inhibition but not the concurrent afferent discharge. Similarly, the cyclooxygenase inhibitor, naproxen, had no effect on the ischaemic afferent response but reduced the intestinal tone shortly from the onset of ischaemia to the early period of reperfusion. These data support a critical role for mast cell-derived histamine in the direct chemoexcitation

  3. Spectral decomposition of pupillary unrest using wavelet entropy.

    PubMed

    Schumann, Andy; Kralisch, Caroline; Bär, Karl-Jürgen

    2015-01-01

    Respiratory and cardiovascular rhythms were discovered in the temporal fluctuations of pupil sizes. The mechanism is physiologically explainable but the potential clinical importance of pupillary unrest has not been studied extensively in the past. Here we analyzed the pupillograms of 29 healthy controls on different time scales and correlated the results to established indices of cardiovascular and cardiorespiratory autonomic function. We discovered a clear lateralization of pupil unrest dependencies. Correlation to vagal heart rate regulation and baroreflex sensitivity indicates the significance of the left pupil's fluctuations evaluating the status of the autonomic nervous system.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Thermal nociceptive properties of trigeminal afferent neurons in rats

    PubMed Central

    2010-01-01

    Background Although nociceptive afferents innervating the body have been heavily studied form many years, much less attention has been paid to trigeminal afferent biology. In particular, very little is known concerning trigeminal nociceptor responses to heat, and almost nothing in the rat. This study uses a highly controlled and reproducible diode laser stimulator to investigate the activation of trigeminal afferents to noxious skin heating. Results The results of this experiment demonstrate that trigeminal thermonociceptors are distinct from themonociceptors innervating the limbs. Trigeminal nociceptors have considerably slower action potential conduction velocities and lower temperature thresholds than somatic afferent neurons. On the other hand, nociceptors innervating both tissue areas separate into those that respond to short pulse, high rate skin heating and those that respond to long pulse, low rate skin heating. Conclusions This paper provides the first description in the literature of the in vivo properties of thermonociceptors in rats. These finding of two separate populations aligns with the separation between C and A-delta thermonociceptors innervating the paw, but have significant differences in terms of temperature threshold and average conduction velocities. An understanding of the temperature response properties of afferent neurons innervating the paw skin have been critical in many mechanistic discoveries, some leading to new pain therapies. A clear understanding of trigeminal nociceptors may be similarly useful in the investigation of trigeminal pain mechanisms and potential therapies. PMID:20609212

  9. 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

  10. 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

  11. Standard deviation of luminance distribution affects lightness and pupillary response.

    PubMed

    Kanari, Kei; Kaneko, Hirohiko

    2014-12-01

    We examined whether the standard deviation (SD) of luminance distribution serves as information of illumination. We measured the lightness of a patch presented in the center of a scrambled-dot pattern while manipulating the SD of the luminance distribution. Results showed that lightness decreased as the SD of the surround stimulus increased. We also measured pupil diameter while viewing a similar stimulus. The pupil diameter decreased as the SD of luminance distribution of the stimuli increased. We confirmed that these results were not obtained because of the increase of the highest luminance in the stimulus. Furthermore, results of field measurements revealed a correlation between the SD of luminance distribution and illuminance in natural scenes. These results indicated that the visual system refers to the SD of the luminance distribution in the visual stimulus to estimate the scene illumination. PMID:25606770

  12. Standard deviation of luminance distribution affects lightness and pupillary response.

    PubMed

    Kanari, Kei; Kaneko, Hirohiko

    2014-12-01

    We examined whether the standard deviation (SD) of luminance distribution serves as information of illumination. We measured the lightness of a patch presented in the center of a scrambled-dot pattern while manipulating the SD of the luminance distribution. Results showed that lightness decreased as the SD of the surround stimulus increased. We also measured pupil diameter while viewing a similar stimulus. The pupil diameter decreased as the SD of luminance distribution of the stimuli increased. We confirmed that these results were not obtained because of the increase of the highest luminance in the stimulus. Furthermore, results of field measurements revealed a correlation between the SD of luminance distribution and illuminance in natural scenes. These results indicated that the visual system refers to the SD of the luminance distribution in the visual stimulus to estimate the scene illumination.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  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. 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

  20. 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

  1. Altered pupillary light reflex in PACAP receptor 1-deficient mice.

    PubMed

    Engelund, Anna; Fahrenkrug, Jan; Harrison, Adrian; Luuk, Hendrik; Hannibal, Jens

    2012-05-01

    The pupillary light reflex (PLR) is regulated by the classical photoreceptors, rods and cones, and by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. IpRGCs receive input from rods and cones and project to the olivary pretectal nucleus (OPN), which is the primary visual center involved in PLR. Mice lacking either the classical photoreceptors or melanopsin exhibit some changes in PLR, whereas the reflex is completely lost in mice deficient of all three photoreceptors. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is co-stored with melanopsin in ipRGCs and mediates light signaling to the brain via the specific PACAP receptor 1 (PAC1R). Here, we examined the occurrence of PACAP and PAC1R in the mouse OPN, and studied if lack of PAC1R affected the PLR. PACAP-immunoreactive nerve fibers were shown in the mouse OPN, and by in situ hybridization histochemistry, we demonstrated the presence of PAC1R mRNA. Mice lacking PAC1R exhibited a significantly attenuated PLR compared to wild type mice upon light stimulation, and the difference became more pronounced as light intensity was increased. Our findings accord well with observations of the PLR in the melanopsin-deficient mouse. We conclude that PACAP/PAC1R signaling is involved in the sustained phase of the PLR at high irradiances.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Prolonged GABAA-mediated inhibition following single hair afferent input to single spinal dorsal horn neurones in cats.

    PubMed

    De Koninck, Y; Henry, J L

    1994-04-01

    To study the central processing mechanisms of sensory input from low threshold afferents to the spinal cord, we examined the excitatory response of single lumbar dorsal horn neurones to stimulation of hairs in the receptive field using a mechanically driven probe, and to activation of single hair follicle afferents using an intracellular current pulse to the cell bodies in the dorsal root ganglion. Experiments were done on anaesthetized, paralysed cats, spinalized at the L1 lumbar level. Responses of spinal neurones to two types of hair afferent input were characteristically different. The excitatory response to input from a single group II hair afferent (A beta; innervating guard hair follicle receptors) was multimodal, characterized by a small early depolarization followed by a sharp, large component with a slow, prolonged decay phase, whereas the response to input from a single group III hair afferent (A delta; innervating down hair follicle receptors) was unimodal. The unitary EPSPs in response to activation of group III hair afferents had a slower rise time and longer decay time constant than those in response to activation of group II hair afferents. When the receptive field of the afferent was located in the centre of the receptive field of the dorsal horn neurone, the gain of the central response was greater for the input from a single group II afferent (> 1) than that for the input from a single group III afferent (< 1). In the case of single group II hair afferents, when pairs of single action potentials or pairs of trains of action potentials were generated at intervals of 20 ms to 3 s, the response in the dorsal horn neurone to the second volley was markedly depressed at intervals of less than 2 s, without any apparent inhibition of the on-going rate of firing. The response to the second volley in single group III afferents was less depressed. This inhibition of the response to the second of a paired volley in single group II hair afferents was

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. The relationship between the size of a muscle afferent volley and the cerebral potential it produces.

    PubMed Central

    Gandevia, S; Burke, D; McKeon, B

    1982-01-01

    This study examined the relationship between the size of an afferent neural input produced by electrical stimulation of the posterior tibial nerve at the ankle and the size of the early components of the evoked cerebral potential. For five of six subjects the first peak of the afferent neural volley recorded in the popliteal fossa was uncontaminated by either motor efferents or cutaneous afferents. This was established by measuring the conduction times of motor fibres in the posterior tibial nerve and cutaneous fibres in the sural and posterior tibial nerves over the ankle to popliteal fossa segment. It is likely therefore that the first peak of the afferent volley contained predominantly, if not exclusively, activity in rapidly conducting afferents from the small muscles of the foot. The size of the two earliest components of the cerebral potential did not increase in direct proportion to the size of the afferent volley which produced it. The early components of the cerebral potential reached a maximum when the responsible muscle afferent volley was less than 50% of its maximum. PMID:6290605

  13. 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

  14. 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

  15. Sequential argon-YAG laser membranotomy of extensive persistent pupillary membrane with visual loss.

    PubMed

    Mansour, Ahmad M; Hamade, Issam; Antonios, Rafic S

    2015-08-25

    A 20-year-old woman, a registered nurse, presented with best-corrected visual acuity of 6/15 (20/50) due to bilateral extensive persistent pupillary membrane. Sequential argon laser photocoagulation of the iris strands at the pupillary membrane iris collarette followed by neodymium:YAG laser lysis resulted in partial clearing of the central visual axis without bleeding. Best-corrected visual acuity improved to 6/9 (20/30) bilaterally without complications noted 1 year after combined laser therapy.

  16. 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

  17. Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation.

    PubMed

    Pinkham, Maximilian I; Barrett, Carolyn J

    2015-06-01

    The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 ± 17% in OVX versus -50 ± 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 ± 11% in OVX vs 62 ± 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway.

  18. 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

  19. 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.

  20. Cryptococcal HSP70 homologue Ssa1 contributes to pulmonary expansion of C. neoformans during the afferent phase of the immune response by promoting macrophage M2 polarization1

    PubMed Central

    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.

    2015-01-01

    Numerous virulence factors expressed by C. neoformans (C. neo) modulate host defenses by promoting non-protective Th2-biased adaptive immune responses. Prior studies demonstrate that the HSP70 homologue, Ssa1, significantly contributes to serotype-D C. neo virulence through the induction of laccase, a Th2-skewing and CNS-tropic factor. In the current study, we sought to determine whether Ssa1 modulates host defenses in mice infected with a highly virulent serotype A (serA) strain of C. neo (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 days. 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, 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. neo, but ultimately has no effect on cryptococcal control by adaptive immunity. PMID:25972480

  1. Non-Linear Neuronal Responses as an Emergent Property of Afferent Networks: A Case Study of the Locust Lobula Giant Movement Detector

    PubMed Central

    Bermúdez i Badia, Sergi; Bernardet, Ulysses; Verschure, Paul F. M. J.

    2010-01-01

    In principle it appears advantageous for single neurons to perform non-linear operations. Indeed it has been reported that some neurons show signatures of such operations in their electrophysiological response. A particular case in point is the Lobula Giant Movement Detector (LGMD) neuron of the locust, which is reported to locally perform a functional multiplication. Given the wide ramifications of this suggestion with respect to our understanding of neuronal computations, it is essential that this interpretation of the LGMD as a local multiplication unit is thoroughly tested. Here we evaluate an alternative model that tests the hypothesis that the non-linear responses of the LGMD neuron emerge from the interactions of many neurons in the opto-motor processing structure of the locust. We show, by exposing our model to standard LGMD stimulation protocols, that the properties of the LGMD that were seen as a hallmark of local non-linear operations can be explained as emerging from the dynamics of the pre-synaptic network. Moreover, we demonstrate that these properties strongly depend on the details of the synaptic projections from the medulla to the LGMD. From these observations we deduce a number of testable predictions. To assess the real-time properties of our model we applied it to a high-speed robot. These robot results show that our model of the locust opto-motor system is able to reliably stabilize the movement trajectory of the robot and can robustly support collision avoidance. In addition, these behavioural experiments suggest that the emergent non-linear responses of the LGMD neuron enhance the system's collision detection acuity. We show how all reported properties of this neuron are consistently reproduced by this alternative model, and how they emerge from the overall opto-motor processing structure of the locust. Hence, our results propose an alternative view on neuronal computation that emphasizes the network properties as opposed to the local

  2. Distinct recurrent versus afferent dynamics in cortical visual processing.

    PubMed

    Reinhold, Kimberly; Lien, Anthony D; Scanziani, Massimo

    2015-12-01

    How intracortical recurrent circuits in mammalian sensory cortex influence dynamics of sensory representation is not understood. Previous methods could not distinguish the relative contributions of recurrent circuits and thalamic afferents to cortical dynamics. We accomplish this by optogenetically manipulating thalamus and cortex. Over the initial 40 ms of visual stimulation, excitation from recurrent circuits in visual cortex progressively increased to exceed direct thalamocortical excitation. Even when recurrent excitation exceeded thalamic excitation, upon silencing thalamus, sensory-evoked activity in cortex decayed rapidly, with a time constant of 10 ms, which is similar to a neuron's integration time window. In awake mice, this cortical decay function predicted the time-locking of cortical activity to thalamic input at frequencies <15 Hz and attenuation of the cortical response to higher frequencies. Under anesthesia, depression at thalamocortical synapses disrupted the fidelity of sensory transmission. Thus, we determine dynamics intrinsic to cortical recurrent circuits that transform afferent input in time.

  3. Renal afferents signaling diuretic activity in the cat.

    PubMed

    Genovesi, S; Pieruzzi, F; Wijnmaalen, P; Centonza, L; Golin, R; Zanchetti, A; Stella, A

    1993-11-01

    Mechanoreceptors and chemoreceptors have been identified inside the kidney, but their functional role is still largely unclear. The aim of this study was to investigate whether changes in urine output could modify the discharge rate of renal afferent fibers. Experiments were performed in anesthetized cats in which afferent renal nerve activity (ARNA) was recorded by standard electrophysiological techniques from a centrally cut renal nerve. Arterial pressure, renal blood flow velocity, urine flow rate, and renal pelvic pressure were also measured. Three diuretic maneuvers were tested in the same cat: intravenous administration of physiological saline (8 to 13 mL/min for 2 minutes), furosemide (1 mg/kg), and atrial natriuretic peptide (ANP, 1 microgram/kg). The three maneuvers increased urine flow rate and pelvic pressure, respectively, 137.0 +/- 20.6% and 136.8 +/- 21.1% (saline), 148.6 +/- 31.7% and 139.6 +/- 43.5% (furosemide), and 75.9 +/- 7.9% and 62.1 +/- 21.2% (ANP) at the time of the maximum response. Arterial pressure slightly increased after saline, did not change after furosemide, and slightly decreased after ANP. Renal blood flow increased after saline and did not change after furosemide and ANP. The three maneuvers increased ARNA by 98.4 +/- 15.2% (saline), 270.7 +/- 100.8% (furosemide), and 59.6 +/- 23.4% (ANP). Changes in ARNA significantly correlate with changes in both pelvic pressure and urine flow rate. Our data demonstrate that increments in urine flow rate increase the firing rate of renal afferent fibers and suggest that (1) pelvic pressure is the major determinant of the neural response, and (2) this increased afferent discharge is due to activation of renal mechanoreceptors.

  4. Excitation of rat colonic afferent fibres by 5-HT3 receptors

    PubMed Central

    Hicks, Gareth A; Coldwell, Jonathan R; Schindler, Marcus; Bland Ward, Philip A; Jenkins, David; Lynn, Penny A; Humphrey, Patrick P A; Blackshaw, L Ashley

    2002-01-01

    The gastrointestinal tract contains most of the body's 5-hydroxytryptamine (5-HT) and releases large amounts after meals or exposure to toxins. Increased 5-HT release occurs in patients with irritable bowel syndrome (IBS) and their peak plasma 5-HT levels correlate with pain episodes. 5-HT3 receptor antagonists reduce symptoms of IBS clinically, but their site of action is unclear and the potential for other therapeutic targets is unexplored. Here we investigated effects of 5-HT on sensory afferents from the colon and the expression of 5-HT3 receptors on their cell bodies in the dorsal root ganglia (DRG). Distal colon, inferior mesenteric ganglion and the lumbar splanchnic nerve bundle (LSN) were placed in a specialized organ bath. Eighty-six single fibres were recorded from the LSN. Three classes of primary afferents were found: 70 high-threshold serosal afferents, four low-threshold muscular afferents and 12 mucosal afferents. Afferent cell bodies were retrogradely labelled from the distal colon to the lumbar DRG, where they were processed for 5-HT3 receptor-like immunoreactivity. Fifty-six percent of colonic afferents responded to 5-HT (between 10−6 and 10−3 M) and 30 % responded to the selective 5-HT3 agonist, 2-methyl-5-HT (between 10−6 and 10−2 M). Responses to 2-methyl-5-HT were blocked by the 5-HT3 receptor antagonist alosetron (2 × 10−7 M), whereas responses to 5-HT were only partly inhibited. Twenty-six percent of L1 DRG cell bodies retrogradely labelled from the colon displayed 5-HT3 receptor-like immunoreactivity. We conclude that colonic sensory neurones expressing 5-HT3 receptors also functionally express the receptors at their peripheral endings. Our data reveal actions of 5-HT on colonic afferent endings via both 5-HT3 and non-5-HT3 receptors. PMID:12411529

  5. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2014-10-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

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

    PubMed

    Gullan, Penny J; Williams, Douglas J

    2016-05-30

    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.

  7. 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

  8. 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…

  9. 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…

  10. [A new method for measuring central activation: fourier analysis of pupillary oscillations in depressed patients].

    PubMed

    Grünberger, J; Linzmayer, L; Grünberger, M; Saletu, B

    1994-01-01

    While the changes in pupillary size during wakefulness and drowsiness are easy to understand, the origin of pupillary oscillations is quite mysterious. Waves of spontaneous pupillary constriction and dilation accompany periods of increasing sleepiness and spontaneous arousal. Lowenstein et al. (1963) demonstrated that in the dark, the pupils of young normal alert subjects show waves of dilatation and contraction lasting from about 4 to 40 s and measuring up to 0.5 mm. Furthermore, superimposed fast and very extensive oscillations were observed. The first described oscillations seemed to reflect central nervous activation. Therefore we analysed pupillary oscillations during the recording period of static pupillometry (described by the authors in 1992) which lasted for 25.6 s. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique which is called "smoothing". Using the Fourier analysis, the spectrum was divided into 5 frequency bands (0.0-0.2; 0.21-0.4; 0.41-0.60; 0.61-0.8; 0.81-1 Hz). We were also interested in the total spectrum. In order to demonstrate utilisation of the new technique, 146 male and female depressed patients (ICD-Diagnosis 296.1, 296.3, 296.1, 296.3 + 300, respectively, 300.4, 301.1, 296.1, 296.3 + 290, respectively), aged between 18 and 45 years, were investigated by means of pupillometry, followed by analysis of pupillary oscillations. The whole group of depressive patients who received antidepressive medication was compared with 64 healthy subjects of similar age to demonstrate differences in the frequency bands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8197747

  11. Macrophages engulf endothelial cell membrane particles preceding pupillary membrane capillary regression

    PubMed Central

    Poché, Ross A.; Hsu, Chih-Wei; McElwee, Melissa L.; Burns, Alan R.; Dickinson, Mary E.

    2015-01-01

    Programmed capillary regression and remodeling are essential developmental processes. However, the cellular and molecular mechanisms that regulate vessel regression are only beginning to be understood. Here, using in vivo, dynamic, confocal imaging of mouse transgenic reporters as well as static confocal and electron microscopy, we studied the embryonic development and postnatal regression of the transient mouse pupillary membrane (PM) vasculature. This approach allowed us to directly observe the precise temporal sequence of cellular events preceding and during the elimination of the PM from the mouse eye. Imaging of Tcf/Lef-H2B::GFP Wnt-reporter mice uncovered that, unlike the hyaloid vasculature of the posterior eye, a PM endothelial cell (EC) Wnt/β-catenin response is unlikely to be part of the regression mechanism. Live imaging of EC and macrophage dynamics revealed highly active Csf1r-GFP+ macrophages making direct contact with the Flk1-myr::mCherry+ vessel surface and with membrane protrusions or filopodia extending from the ECs. Flk1-myr::mCherry+ EC membrane particles were observed on and around ECs as well as within macrophages. Electron microscopy studies confirmed that they were in phagosomes within macrophages, indicating that the macrophages engulfed the membrane particles. Interestingly, EC plasma membrane uptake by PM macrophages did not correlate with apoptosis and was found shortly after vessel formation at mid-gestation stages in the embryo; long before vessel regression begins during postnatal development. Additionally, genetic ablation of macrophages showed that EC membrane particles were still shed in the absence of macrophages suggesting that macrophages do not induce the formation or release of EC microparticles. These studies have uncovered a novel event during programmed capillary regression in which resident macrophages scavenge endothelial cell microparticles released from the PM vessels. This finding suggests that there may be an

  12. Piezo2 expression in corneal afferent neurons.

    PubMed

    Bron, Romke; Wood, Rhiannon J; Brock, James A; Ivanusic, Jason J

    2014-09-01

    Recently, a novel class of mechanically sensitive channels has been identified and have been called Piezo channels. In this study, we explored Piezo channel expression in sensory neurons supplying the guinea pig corneal epithelium, which have well-defined modalities in this species. We hypothesized that a proportion of corneal afferent neurons express Piezo2, and that these neurons are neurochemically distinct from corneal polymodal nociceptors or cold-sensing neurons. We used a combination of retrograde tracing to identify corneal afferent neurons and double label in situ hybridization and/or immunohistochemistry to determine their molecular and/or neurochemical profile. We found that Piezo2 expression occurs in ∼26% of trigeminal ganglion neurons and 30% of corneal afferent neurons. Piezo2 corneal afferent neurons are almost exclusively non-calcitonin gene-related peptide (CGRP)-immunoreactive (-IR), medium- to large-sized neurons that are NF200-IR, suggesting they are not corneal polymodal nociceptors. There was no coexpression of Piezo2 and transient receptor potential cation channel subfamily M member 8 (TRPM8) transcripts in any corneal afferent neurons, further suggesting that Piezo2 is not expressed in corneal cold-sensing neurons. We also noted that TRPM8-IR or CGRP-IR corneal afferent neurons are almost entirely small and lack NF200-IR. Piezo2 expression occurs in a neurochemically distinct subpopulation of corneal afferent neurons that are not polymodal nociceptors or cold-sensing neurons, and is likely confined to a subpopulation of pure mechano-nociceptors in the cornea. This provides the first evidence in an in vivo system that Piezo2 is a strong candidate for a channel that transduces noxious mechanical stimuli.

  13. 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

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

    PubMed

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

    2012-10-01

    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.

  15. 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

  16. 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

  17. Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique.

    PubMed

    Aghajanian, G K; Wang, R Y

    1977-02-18

    Afferents to th midbrain dorsal and median raphe nuclei in the rat were studied by means of the horseradish peroxidase (HRP) retrograde transport method. The HRP was given by means of a modified iontophoretic delivery technique. This technique permitted an efficient and localized deposition of a high concentration of HRP into the raphe nuclei. Afferents to the raphe as determined by this method could be categorized into 2 classes; those exclusively to the raphe and those also positive for adjacent reticular formation. The most striking afferent area to the raphe, both in terms of selectivity and density, was the lateral habenula. This result is in accord with previous studies using degeneration methods which indicate an habenular projection to the raphe area. There were afferents exclusively positive for the dorsal raphe nucleus emanating from the nucleus of the solitary tract. Most other raphe afferent areas were also positive for the reticular formation (e.g;, prefrontal cortex, medial forebrain bundle, preoptic nuclei, and reticular formation). The existence of a major afferent system from the lateral habenula to the midbrain raphe is consistent with the concept of a "dorsal pathway" which might be responsible for relaying information from forebrain limbic structures to the "midbrain limbic areas".

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

    PubMed

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

    2006-03-01

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

  19. Single low-threshold afferents innervating the skin of the human foot modulate ongoing muscle activity in the upper limbs.

    PubMed

    Bent, Leah R; Lowrey, Catherine R

    2013-03-01

    We have shown for the first time that single cutaneous afferents in the foot dorsum have significant reflex coupling to motoneurons supplying muscles in the upper limb, particularly posterior deltoid and triceps brachii. These observations strengthen what we know from whole nerve stimulation, that skin on the foot and ankle can contribute to the modulation of interlimb muscles in distant innervation territories. The current work provides evidence of the mechanism behind the reflex, where one single skin afferent can evoke a reflex response, rather than a population. Nineteen of forty-one (46%) single cutaneous afferents isolated in the dorsum or plantar surface of the foot elicited a significant modulation of muscle activity in the upper limb. Identification of single afferents in this reflex indicates the strength of the connection and, ultimately, the importance of foot skin in interlimb coordination. The median response magnitude was 2.29% of background EMG, and the size of the evoked response did not significantly differ among the four mechanoreceptor classes (P > 0.1). Interestingly, although the distribution of afferents types did not differ across the foot dorsum, there was a significantly greater coupling response from receptors located on the medial aspect of the foot dorsum (P < 0.01). Furthermore, the most consistent coupling with upper limb muscles was demonstrated by type I afferents (fast and slowly adapting). This work contributes to the current literature on receptor specificity, supporting the view that individual classes of cutaneous afferents may subserve specific roles in kinesthesia, reflexes, and tactile perception.

  20. 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

  1. 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.

  2. Identified proprioceptive afferents and motor rhythm entrainment in the crayfish walking system.

    PubMed

    Elson, R C; Sillar, K T; Bush, B M

    1992-03-01

    1. In crayfish, Pacifastacus leniusculus, remotion of a walking leg stretches the thoraco-coxal (TC) muscle receptor organ (TCMRO), located at the leg's articulation with the thorax. In vitro, alternate stretch and release of the fourth leg's TCMRO entrained the centrally generated rhythmic motor output to that leg, with the remotor phase of the rhythm entraining to TCMRO stretch, the promoter phase to release. This coordination of motor bursts to afferent input corresponds to that of active, rhythmic movements in vivo. 2. Entrainment was rapid in onset (stable coordination resulting within the first or second stimulus cycle) and was relatively phase-constant (whatever the stimulus frequency, during 1:1 entrainment, remotor bursts began near the onset of stretch and promotor bursts began near the onset of release). Outside the range of 1:1 entrainment, 2:1, 1:2, and 1:3 coordination ratios (rhythm:stimulus) were encountered. Resetting by phasic stimulation of the TCMRO was complete and probabilistic: effective stimuli triggered rapid transitions between the two burst phases. 3. The TCMRO is innervated by two afferents, the nonspiking S and T fibers, which generate graded depolarizing receptor potentials in response to stretch. During proprioceptive entrainment, the more phasic T fiber depolarized and hyperpolarized more rapidly or in advance of the more tonic S fiber. These receptor potentials were modified differently in the two afferents by interaction with central synaptic inputs that were phase-locked to the entrained motor rhythm. 4. Injecting slow sinusoidal current into either afferent alone could entrain motor rhythms: promoter phase bursts were entrained to depolarization of the S fiber or hyperpolarization of the T fiber, whereas the converse response was obtained for remotor phase bursts. 5. During proprioceptive entrainment, tonic hyperpolarization of the S fiber weakened entrained promotor bursts and allowed remotor burst durations to increase

  3. 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

  4. 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

  5. The unsilent majority-TRPV1 drives "spontaneous" transmission of unmyelinated primary afferents within cardiorespiratory NTS.

    PubMed

    Andresen, Michael C; Hofmann, Mackenzie E; Fawley, Jessica A

    2012-12-15

    Cranial primary afferent sensory neurons figure importantly in homeostatic control of visceral organ systems. Of the two broad classes of visceral afferents, the role of unmyelinated or C-type class remains poorly understood. This review contrasts key aspects of peripheral discharge properties of C-fiber afferents and their glutamate transmission mechanisms within the solitary tract nucleus (NTS). During normal prevailing conditions, most information arrives at the NTS through myelinated A-type nerves. However, most of visceral afferent axons (75-90%) in NTS are unmyelinated, C-type axons. Centrally, C-type solitary tract (ST) afferent terminals have presynaptic transient receptor potential vanilloid type 1 (TRPV1) receptors. Capsaicin activation of TRPV1 blocks phasic or synchronous release of glutamate but facilitates release of glutamate from a separate pool of vesicles. This TRPV1-operated pool of vesicles is active at normal temperatures and is responsible for actively driving a 10-fold higher release of glutamate at TRPV1 compared with TRPV1- terminals even in the absence of afferent action potentials. This novel TRPV1 mechanism is responsible for an additional asynchronous release of glutamate that is not present in myelinated terminals. The NTS is rich with presynaptic G protein-coupled receptors, and the implications of TRPV1-operated glutamate offer unique targets for signaling in C-type sensory afferent terminals from neuropeptides, inflammatory mediators, lipid metabolites, cytokines, and cannabinoids. From a homeostatic view, this combination could have broad implications for integration in chronic pathological disturbances in which the numeric dominance of C-type endings and TRPV1 would broadly disturb multisystem control mechanisms.

  6. Short latency activation of pyramidal tract cells by Group I afferent volleys in the cat

    PubMed Central

    Swett, John E.; Bourassa, Charles M.

    1967-01-01

    1. The contralateral bulbar pyramids were explored with low impedance micro-electrodes in cats anaesthetized with chloralose to reveal the effect of Group I afferent volleys (deep radial nerve of the forelimb) on pyramidal tract (Pt) cells. 2. Low rate (0·5/sec) stimulation of Group I afferents produced small responses (5-30 μV) in the bulbar pyramid which could be detected only with response averaging methods. The responses appeared with an initial latency of 7·0-11·2 msec and reached peak amplitude in 15·7 msec (mean latency). The pyramidal tract origin of the potential was demonstrated by its depression at stimulus rates above 1-2 sec and its disappearance at rates above 4/sec. 3. Recordings of neurones in the Group I cortical projection zone of the posterior sigmoid gyrus revealed that several types of cells, including Pt cells, were activated by Group I afferent volleys. 4. Pt cells responding to Group I afferent volleys frequently received convergent actions from low threshold cutaneous nerve volleys. 5. Averaged response recordings from electrodes positioned in the medial portions of the lateral funiculus of the spinal cord at the level of C2, revealed a response to Group I afferent volleys as early as 7·4 msec which possessed the same characteristics as the relayed response to Group I in the bulbar pyramids. Some Pt cells, activated by Group I volleys orthodromically, could also be antidromically activated by stimulation of the recording site in C2. 6. It was concluded that group I afferent volleys can influence, after short latencies, Pt and non-Pt cells and that some of these Pt cells gave rise to axons incorporated in the corticospinal tract. PMID:16992239

  7. 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

  8. [Multiple ocular coloboma (MOC) with persistent pupillary membrane in the snow leopard (Panthera uncia)].

    PubMed

    Schäffer, E; Wiesner, H; von Hegel, G

    1988-01-01

    In a litter of three snow leopards, bilateral colobomata of the upper temporal eyelids, bilateral persistent pupillary membranes and a unilateral coloboma of the optic nerve entrance are described as "Multiple Ocular Colobomata" (MOC). The causal pathogenesis of each of the colobomata is discussed comparatively. The colobomata of the eyelids, essential feature of the MOC syndrome in snow leopards, are most probably not of hereditary, but rather of intrauterine infectious viral origin.

  9. [Multiple ocular coloboma (MOC) with persistent pupillary membrane in the snow leopard (Panthera uncia)].

    PubMed

    Schäffer, E; Wiesner, H; von Hegel, G

    1988-01-01

    In a litter of three snow leopards, bilateral colobomata of the upper temporal eyelids, bilateral persistent pupillary membranes and a unilateral coloboma of the optic nerve entrance are described as "Multiple Ocular Colobomata" (MOC). The causal pathogenesis of each of the colobomata is discussed comparatively. The colobomata of the eyelids, essential feature of the MOC syndrome in snow leopards, are most probably not of hereditary, but rather of intrauterine infectious viral origin. PMID:3368914

  10. 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

  11. 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

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

    PubMed

    Kiyatkin, Michael E; Feng, Bin; Schwartz, Erica S; Gebhart, G F

    2013-11-01

    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.

  13. Patterns of saccular afferent innervation in sciaenids.

    PubMed

    Selckmann, G M; Ramcharitar, J

    2013-09-01

    In this study, saccular afferent arborization patterns in Atlantic croaker Micropogonias undulatus, red drum Sciaenops ocellatus and spot Leiostomus xanthurus were characterized. Leiostomus xanthurus showed the simplest configuration while M. undulatus displayed the most complex. In addition, hair-cell densities at sites sampled along the rostro-caudal axis of the saccular epithelia correlated with the observed patterns of arborization. PMID:23991887

  14. 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

  15. 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

  16. 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

  17. 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

  18. Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response

    PubMed Central

    Barrionuevo, Pablo A.; Cao, Dingcai

    2016-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a “winner-takes-all” process, suggesting the integration with PC signals might be mediated by a postretinal site. PMID:27690169

  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.

  20. 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

  1. 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.

  2. 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…

  3. 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

  4. A High-Salt Diet Differentially Modulates Mechanical Activity of Afferent and Efferent Collecting Lymphatics in Murine Iliac Lymph Nodes

    PubMed Central

    Mizuno, Risuke; Ono, Nobuyuki; Nishimoto, Mitsuhiro; Fujita, Toshiro

    2015-01-01

    Abstract Background: The lymphatic system contributes to fluid homeostasis in various tissues. Recent evidence suggests that lymphangiogenesis induced by a high-salt diet (HSD) is associated with blood pressure regulation. Lymph nodes, located along lymphatic pathways, are not only important secondary lymphoid tissues for cancer metastasis, inflammation, and immune responses, but are also important for fluid homeostasis. Afferent lymphatics collect lymph from the pre-nodal area and efferent lymphatics drain lymph out of the lymph nodes. However, the difference in mechanical activity between afferent and efferent lymphatics and the effect of a HSD on these vessels have not been shown. Methods and Results: Changes in mechanical activity of isolated afferent and efferent lymphatics in normal salt diet (NSD) and 4-week HSD mice in response to increases in intraluminal pressures from 3 to 7 cmH2O were measured using video-microscopy. The higher intramural pressure equivalently decreased pumping activity of afferent and efferent lymphatics in NSD mice. A HSD suppressed the amplitude, ejection fraction, and stroke volume of afferent lymphatics, leading to marked reductions in pumping activity. In contrast, the pumping activities of efferent lymphatics were resistant to a HSD and were preserved by enhancing the contraction frequency. Conclusions: A HSD differentially modulated the mechanical activity of afferent and efferent collecting lymphatics in murine iliac lymph nodes. PMID:26091404

  5. Interactions between visceral afferent signaling and stimulus processing.

    PubMed

    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

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

    PubMed

    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

  7. 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

  8. 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

  9. Central pupillary light reflex circuits in the cat: I. The olivary pretectal nucleus.

    PubMed

    Sun, Wensi; May, Paul J

    2014-12-15

    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 the 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.

  10. 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

  11. 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.

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

    PubMed

    Feng, Bin; 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

  13. 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

  14. Activation of intestinal spinal afferent endings by changes in intra-mesenteric arterial pressure

    PubMed Central

    Humenick, A; Chen, B N; Wiklendt, L; Spencer, N J; Zagorodnyuk, V P; Dinning, P G; Costa, M; Brookes, S J H

    2015-01-01

    Spinal sensory neurons innervate many large blood vessels throughout the body. Their activation causes the hallmarks of neurogenic inflammation: vasodilatation through the release of the neuropeptide calcitonin gene-related peptide and plasma extravasation via tachykinins. The same vasodilator afferent neurons show mechanical sensitivity, responding to crushing, compression or axial stretch of blood vessels – responses which activate pain pathways and which can be modified by cell damage and inflammation. In the present study, we tested whether spinal afferent axons ending on branching mesenteric arteries (‘vascular afferents’) are sensitive to increased intravascular pressure. From a holding pressure of 5 mmHg, distension to 20, 40, 60 or 80 mmHg caused graded, slowly adapting increases in firing of vascular afferents. Many of the same afferent units showed responses to axial stretch, which summed with responses evoked by raised pressure. Many vascular afferents were also sensitive to raised temperature, capsaicin and/or local compression with von Frey hairs. However, responses to raised pressure in single, isolated vessels were negligible, suggesting that the adequate stimulus is distortion of the arterial arcade rather than distension per se. Increasing arterial pressure often triggered peristaltic contractions in the neighbouring segment of intestine, an effect that was mimicked by acute exposure to capsaicin (1 μm) and which was reduced after desensitisation to capsaicin. These results indicate that sensory fibres with perivascular endings are sensitive to pressure-induced distortion of branched arteries, in addition to compression and axial stretch, and that they contribute functional inputs to enteric motor circuits. PMID:26010893

  15. The organization of primary afferent depolarization in the isolated spinal cord of the frog

    PubMed Central

    Carpenter, D. O.; Rudomin, P.

    1973-01-01

    1. The organization of primary afferent depolarization (PAD) produced by excitation of peripheral sensory and motor nerves was studied in the frog cord isolated with hind limb nerves. 2. Dorsal root potentials from sensory fibres (DR-DRPs) were evoked on stimulation of most sensory nerves, but were largest from cutaneous, joint and flexor muscle afferents. With single shock stimulation the largest cutaneous and joint afferent fibres gave DR-DRPs, but potentials from muscle nerves resulted from activation of sensory fibres with thresholds to electrical stimulation higher than 1·2-1·5 times the threshold of the most excitable fibres in the nerve. This suggests that PAD from muscle afferents is probably due to excitation of extrafusal receptors. 3. Dorsal root potentials produced by antidromic activation of motor fibres (VR-DRPs) were larger from extensor muscles and smaller or absent from flexor muscles. The VR-DRPs were produced by activation of the lowest threshold motor fibres. 4. Three types of interactions were found between test and conditioning DRPs from the same or different nerves. With maximal responses occlusion was usually pronounced. At submaximal levels linear summation occurred. Near threshold the conditioning stimulus frequently resulted in a large facilitation of the test DRP. All three types of interactions were found with two DR-DRPs, two VR-DRPs or one DR-DRP and one VR-DRP. 5. The excitability of sensory nerve terminals from most peripheral nerves was increased during the DR-DRP. The magnitude of the excitability increase varied roughly with the magnitude of the DR-DRP evoked by the conditioning stimulus. 6. There was a marked excitability increase of cutaneous and extensor muscle afferent terminals during the VR-DRP. Flexor muscle afferent terminals often showed no excitability changes to ventral root stimulation. In those experiments where afferent terminals from flexor muscles did show an excitability increase, the effects were smaller than

  16. 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

  17. 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

  18. 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.

  19. Synaptic transmission of baro- and chemoreceptors afferents in the NTS second order neurons.

    PubMed

    Accorsi-Mendonça, Daniela; Machado, Benedito H

    2013-04-01

    Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise timing synaptic transmission. Since 2nd-order NTS neurons receiving baroreceptors inputs are relatively well characterized, their electrophysiological profile has been accepted as a general characteristic for all 2nd-order NTS neurons involved with the processing of different sensorial inputs. On the other hand, the synaptic properties of other afferent systems in NTS, such as the peripheral chemoreceptors, are not yet well understood. In this context, in previous studies we demonstrated that in response to repetitive afferents stimulation, the chemoreceptors 2nd-order NTS neurons also presented high fidelity of synaptic transmission, but with a large variability in the latency of evoked responses. This finding is different in relation to the precise timing transmission for baroreceptor 2nd-order NTS neurons, which was accepted as a general characteristic profile for all 2nd order neurons in the NTS. In this brief review we discuss this new concept as an index of complexity of the sensorial inputs to NTS with focus on the synaptic processing of baro- and chemoreceptor afferents.

  20. 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

  1. 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

  2. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. Inflammation increases the excitability of masseter muscle afferents.

    PubMed

    Harriott, A M; Dessem, D; Gold, M S

    2006-08-11

    Temporomandibular disorder is a major health problem associated with chronic orofacial pain in the masticatory muscles and/or temporomandibular joint. Evidence suggests that changes in primary afferents innervating the muscles of mastication may contribute to temporomandibular disorder. However, there has been little systematic study of the mechanisms controlling the excitability of these muscle afferents, nor their response to inflammation. In the present study, we tested the hypotheses that inflammation increases the excitability of sensory neurons innervating the masseter muscle of the rat and that the ionic mechanisms underlying these changes are unique to these neurons. We examined inflammation-induced changes in the excitability of trigeminal ganglia muscle neurons following intramuscular injections of complete Freund's adjuvant. Three days after complete Freund's adjuvant injection acutely dissociated, retrogradely labeled trigeminal ganglia neurons were studied using whole cell patch clamp techniques. Complete Freund's adjuvant-induced inflammation was associated with an increase in neuronal excitability marked by a significant decrease in rheobase and increase in the slope of the stimulus response function assessed with depolarizing current injection. The increase in excitability was associated with significant decreases in the rate of action potential fall and the duration of the action potential afterhyperpolarization. These changes in excitability and action potential waveform were associated with significant shifts in the voltage-dependence of activation and steady-state availability of voltage-gated K(+) current as well as significant decreases in the density of voltage-gated K(+) current subject to steady-state inactivation. These data suggest that K(+) channel subtypes may provide novel targets for the treatment of pain arising from inflamed muscle. These results also support the hypothesis that the underlying mechanisms of pain arising from

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Irregular primary otolith afferents from the guinea pig utricular and saccular maculae respond to both bone conducted vibration and to air conducted sound.

    PubMed

    Curthoys, Ian S; Vulovic, Vedran; Sokolic, Ljiljana; Pogson, Jacob; Burgess, Ann M

    2012-10-01

    This study sought to identify in guinea pig the peripheral sense organ of origin of otolith irregular primary vestibular afferent neurons having a very sensitive response to both air-conducted sound (ACS) and bone-conducted vibration (BCV). Neurons responding to both types of stimuli were labelled by juxtacellular labelling by neurobiotin. Whole mounts of the maculae showed that some vestibular afferents activated by both ACS and BCV originate from the utricular macula and some from the saccular macula - there is no "afferent specificity" by one sense organ for ACS and the other for BCV - instead some afferents from both sense organs have sensitive responses to both stimuli. The clinical implication of this result is that differential evaluation of the functional status of the utricular and saccular maculae cannot rely on stimulus type (ACS vs BCV), however the differential motor projections of the utricular and saccular maculae allow for differential evaluation of each sense organ.

  11. Irregular primary otolith afferents from the guinea pig utricular and saccular maculae respond to both bone conducted vibration and to air conducted sound.

    PubMed

    Curthoys, Ian S; Vulovic, Vedran; Sokolic, Ljiljana; Pogson, Jacob; Burgess, Ann M

    2012-10-01

    This study sought to identify in guinea pig the peripheral sense organ of origin of otolith irregular primary vestibular afferent neurons having a very sensitive response to both air-conducted sound (ACS) and bone-conducted vibration (BCV). Neurons responding to both types of stimuli were labelled by juxtacellular labelling by neurobiotin. Whole mounts of the maculae showed that some vestibular afferents activated by both ACS and BCV originate from the utricular macula and some from the saccular macula - there is no "afferent specificity" by one sense organ for ACS and the other for BCV - instead some afferents from both sense organs have sensitive responses to both stimuli. The clinical implication of this result is that differential evaluation of the functional status of the utricular and saccular maculae cannot rely on stimulus type (ACS vs BCV), however the differential motor projections of the utricular and saccular maculae allow for differential evaluation of each sense organ. PMID:22814095

  12. 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

  13. Baroreceptor afferents modulate brain excitation and influence susceptibility to toxic effects of hyperbaric oxygen.

    PubMed

    Demchenko, Ivan T; Gasier, Heath G; Zhilyaev, Sergei Yu; Moskvin, Alexander N; Krivchenko, Alexander I; Piantadosi, Claude A; Allen, Barry W

    2014-09-01

    Unexplained adjustments in baroreflex sensitivity occur in conjunction with exposures to potentially toxic levels of hyperbaric oxygen. To investigate this, we monitored central nervous system, autonomic and cardiovascular responses in conscious and anesthetized rats exposed to hyperbaric oxygen at 5 and 6 atmospheres absolute, respectively. We observed two contrasting phases associated with time-dependent alterations in the functional state of the arterial baroreflex. The first phase, which conferred protection against potentially neurotoxic doses of oxygen, was concurrent with an increase in baroreflex sensitivity and included decreases in cerebral blood flow, heart rate, cardiac output, and sympathetic drive. The second phase was characterized by baroreflex impairment, cerebral hyperemia, spiking on the electroencephalogram, increased sympathetic drive, parasympatholysis, and pulmonary injury. Complete arterial baroreceptor deafferentation abolished the initial protective response, whereas electrical stimulation of intact arterial baroreceptor afferents prolonged it. We concluded that increased afferent traffic attributable to arterial baroreflex activation delays the development of excessive central excitation and seizures. Baroreflex inactivation or impairment removes this protection, and seizures may follow. Finally, electrical stimulation of intact baroreceptor afferents extends the normal delay in seizure development. These findings reveal that the autonomic nervous system is a powerful determinant of susceptibility to sympathetic hyperactivation and seizures in hyperbaric oxygen and the ensuing neurogenic pulmonary injury.

  14. 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

  15. Projection of cat jaw muscle spindle afferents related to intrafusal fibre influence.

    PubMed

    Taylor, A; Durbaba, R; Rodgers, J F

    1993-06-01

    1. A method of classification of muscle spindle afferents using succinylcholine (SCh) and ramp stretches has recently been described, which appears to estimate separately the strength of influence of bag1 (b1) and of bag2 (b2) intrafusal fibres. Increase in dynamic difference (delta DD) indicates b1 influence whilst increase in initial frequency (delta IF) indicates b2 influence. The significance of this classification has now been examined by correlation with the strength of synaptic projection of jaw muscle spindle afferents to the fifth motor nucleus (MotV) and the supratrigeminal region (STR) in anaesthetized cats. 2. Projection strength was estimated by computing the extracellular focal synaptic potential (FSP) from spike-triggered averages of 1024 sweeps at 100 microns intervals along tracks through STR and MotV. Trigger pulses were derived from spindle afferent cell bodies of the jaw-closer muscles recorded in the mesencephalic trigeminal nucleus, and characterized by the effect of SCh on their responses to ramp-and-hold stretches. 3. The maximum size of FSPs in tracks traversing STR and MotV ranged from 2.08 to 36.99 microV with a mean of 7.55 microV. The amplitudes were bimodally distributed into roughly equal-sized groups with high and low amplitude FSPs. 4. Mean values of delta IF were significantly greater for the group with large FSPs than for those with small FSPs. There were no significant differences in delta DD. FSP amplitude was significantly positively correlated with delta IF, but not with delta DD. 5. Spindle afferents with high values of FSP amplitude in MotV had a wide range of values of delta DD (b1b2c and b2c groups), while units with large FSPs in STR were all in the b2c category. Some evidence is presented to indicate that this reflects a preferential projection of secondary afferents to the STR. 6. For those units with projection to both STR and to MotV, there was a significant positive correlation between FSP amplitude in the two nuclei

  16. Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients.

    PubMed

    Hughes, Patrick A; Moretta, Melissa; Lim, Amanda; Grasby, Dallas J; Bird, Daniel; Brierley, Stuart M; Liebregts, Tobias; Adam, Birgit; Blackshaw, L Ashley; Holtmann, Gerald; Bampton, Peter; Hoffmann, Peter; Andrews, Jane M; Zola, Heddy; Krumbiegel, Doreen

    2014-11-01

    Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS. PMID:25063707

  17. Impaired nitric oxide-independent dilation of renal afferent arterioles in spontaneously hypertensive rats.

    PubMed

    Hayashi, K; Matsuda, H; Nagahama, T; Fujiwara, K; Ozawa, Y; Kubota, E; Honda, M; Tokuyama, H; Saruta, T

    1999-03-01

    Sustained hypertension alters vasomotor regulation in various vascular beds. We studied whether nitric oxide (NO)-dependent and NO-independent vasodilator mechanisms are altered in renal microvessels in hypertension. To directly visualize the renal microcirculation, the isolated perfused hydronephrotic rat kidney model was used. After pretreatment with indomethacin (100 micromol/l), afferent arterioles were constricted by norepinephrine (NE) or by increasing renal arterial pressure (i.e., myogenic constriction; from 80 to 180 mmHg). Acetylcholine (ACH) was then added, and the renal microvascular response was assessed by computer-assisted video image analysis. A similar protocol was conducted in the presence of nitro-L-arginine methylester (L-NAME; 100 micromol/l). During NE constriction, ACH caused dose-dependent and sustained vasodilation of the afferent arteriole, similar in magnitude in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the presence of L-NAME, ACH (0.01-1 micromol/l) elicited only transient dilation, and the degree of vasodilation was very low in SHR. During myogenic constriction, afferent arterioles from WKY and SHR kidneys responded to ACH with only transient vasodilation, which was unaffected by NO inhibition; the transient vasodilative responses elicited by ACH (0.1-1 micromol/l) were smaller in SHR than in WKY. In conclusion, ACH has both sustained and transient vasodilative effects on the afferent arteriole. Sustained vasodilation is attributed to NO generation, which is similar in WKY and SHR. In contrast, transient vasodilation, mediated by NO-independent vasodilator factors, is impaired in SHR. Deranged vasodilatory mechanisms in hypertension may disturb the renal microcirculation, which may result in renal injury.

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

    PubMed

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

    2015-04-01

    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

  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. Neuronal activity of the cat supraoptic nucleus is influenced by muscle small-diameter afferent (groups III and IV) receptors.

    PubMed

    Kannan, H; Yamashita, H; Koizumi, K; Brooks, C M

    1988-08-01

    In anesthetized cats, responses of single neurosecretory neurons of the supraoptic nucleus to activation of muscle receptors were investigated. Electrical stimulation (1-3 pulses at 200 Hz) of group III and IV pure muscle afferents (gastrocnemius nerve) evoked excitation of greater than 50% of supraoptic nucleus neurons (n = 50), whereas stimulation of group Ia or Ib fibers was ineffective. Baroreceptor stimulation inhibited 95% of these supraoptic nucleus neurons that responded to activation of muscle afferents. Excitation of receptors in the gastrocnemius muscle by intra-arterial injection of chemicals (NaCl, KCl, and bradykinin) increased firing rates of most (84%, 74%, and 80%, respectively) neurosecretary neurons. The magnitude of the excitatory response was dose dependent--bradykinin being the most effective. The response disappeared after muscle denervation. When the gastrocnemius muscle alone was contracted phasically by ventral root stimulation, discharges of the supraoptic nucleus neurons increased, whereas quick stretch of the muscle had no effect. We conclude that activation of muscle receptors by chemical or mechanical stimulus can directly excite neurosecretory neurons in the supraoptic nucleus and that afferent impulses are carried by polymodal fibers of small diameter but not by the largest afferents (group I) from the muscle. The results may relate to increased concentrations of plasma vasopressin during exercise.

  1. 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

  2. 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

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

    PubMed

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

    2013-01-15

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

  4. 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.

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

    PubMed Central

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

    2014-01-01

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

  6. Afferent pathways of neural reno-renal reflexes controlling sodium and water excretion in the cat.

    PubMed

    Golin, R; Genovesi, S; Stella, A; Zanchetti, A

    1987-08-01

    We have studied the role of afferent renal nerve fibres in anaesthetized cats in mediating the decrease in sodium and water excretion from the contralateral kidney caused by unilateral renal denervation. Transient denervation of one kidney obtained by cooling of the left renal nerves increases contralateral efferent renal nerve activity and decreased sodium and water excretion from the opposite kidney. The results observed in animals with intact neural pathways were compared with those obtained after the left kidney had been selectively deafferentated by cutting the dorsal roots from T9 to L4. Bilateral section of dorsal roots did not affect the increase in sodium and water excretion from the transiently denervated left kidney, but entirely abolished the decrease in sodium and water excretion from the contralateral kidney. Neither the left nor the right dorsal root section alone, affected the response of the contralateral right kidney. Our data demonstrate that afferent renal nerve fibres project bilaterally to the spinal cord and form the afferent branch of the reno-renal reflex by which one kidney can control the function of the opposite one.

  7. ATP decreases mechanical sensitivity of muscle thin-fiber afferents in rats.

    PubMed

    Matsuda, Teru; Kubo, Asako; Taguchi, Toru; Mizumura, Kazue

    2015-08-01

    ATP is an energy rich substance contained in cells in the order of mM. It is released when cells are damaged and when muscle is compressed or contracted. Subcutaneous injection of ATP induces pain-related behavior and hyperalgesia to mechanical and heat stimulation in rats. However, the effects of ATP in muscle have not been fully studied. In the present study we examined the effects of ATP on muscle C-fiber afferent activities using single fiber recordings, and on nociceptive behavior. Muscle C-fiber activities were recorded in vitro using extensor digitorum longus muscle-common peroneal nerve preparations excised from rats deeply anesthetized with pentobarbital. ATP (100 μM and 1 mM, but not 1 μM) superfused for 5 min before the mechanical stimulation suppressed the mechanical responses of muscle thin fibers irrespective of whether they excited the fiber. This suppressive effect was reversed by P2X receptor antagonists PPADS (100 μM) and suramin (300 μM). We also found that subcutaneous injection of ATP (10 mM) induced nociceptive behavior, whereas intramuscular injection had no effect. These findings showed that effects of ATP on muscle afferents differ from those on cutaneous afferents.

  8. 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.

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

    PubMed

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

    2014-05-21

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

  10. 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

  11. Targeting primary afferent nerves for novel antitussive therapy.

    PubMed

    Undem, Bradley J; Carr, Michael J

    2010-01-01

    The best available data support the hypothesis that there are at least two types of vagal nerves responsible for initiating coughing reflexes. One type of nerve conducts action potentials in the A-range and is characterized by rapidly adapting responses to mechanical probing or acidification of the large airway epithelium. Stimulation of these nerves can evoke cough in unconscious experimental animals and humans. These nerves are important in immediate cough evoked by aspiration and as such perform a critical role in airway defense. The other type of primary afferent nerve involved in cough is the vagal C-fiber. Inhalation of selective C-fiber stimulants leads to cough only in conscious animals. In clinical studies, inhalation of a low concentration of a C-fiber stimulant causes an irritating, itchy urge-to-cough sensation that mimics the urge-to-cough sensations associated with respiratory tract infection, post-infection, gastroesophageal reflux disorders, and inflammatory airway diseases. Here we discuss the recent advances in sensory neurobiology that allow for the targeting of vagal C-fibers for novel antitussive therapy. No attempts are made to be all-inclusive with respect to the numerous possible molecular targets being considered to accomplish this goal. Rather, two general strategies are discussed: decreasing generator potential amplitude and decreasing the efficiency by which a generator potential evokes action-potential discharge. For the first category we focus on two targets, transient receptor potential vanilloid 1 and transient receptor potential A1. For the latter category we focus on recent advances in voltage-gated sodium (Na(V)) channel biology.

  12. Adipose afferent reflex: sympathetic activation and obesity hypertension.

    PubMed

    Xiong, X-Q; Chen, W-W; Zhu, G-Q

    2014-03-01

    Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.

  13. 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

  14. Differential presynaptic control of the synaptic effectiveness of cutaneous afferents evidenced by effects produced by acute nerve section

    PubMed Central

    Rudomin, P; Jiménez, I; Chávez, D

    2013-01-01

    In the anaesthetized cat, the acute section of the saphenous (Saph) and/or the superficial peroneal (SP) nerves was found to produce a long-lasting increase of the field potentials generated in the dorsal horn by stimulation of the medial branch of the sural (mSU) nerve. This facilitation was associated with changes in the level of the tonic primary afferent depolarization (PAD) of the mSU intraspinal terminals. The mSU afferent fibres projecting into Rexed's laminae III–IV were subjected to a tonic PAD that was reduced by the acute section of the SP and/or the Saph nerves. The mSU afferents projecting deeper into the dorsal horn (Rexed's laminae V–VI) were instead subjected to a tonic PAD that was increased after Saph and SP acute nerve section. A differential control of the synaptic effectiveness of the low-threshold cutaneous afferents according to their sites of termination within the dorsal horn is envisaged as a mechanism that allows selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks. PMID:23478136

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

    Hudson, Kathryn M.; Condon, Melia; Ackerley, Rochelle; McGlone, Francis; Olausson, Håkan; Birznieks, Ingvars

    2015-01-01

    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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. The classification of afferents from muscle spindles of the jaw-closing muscles of the cat.

    PubMed

    Taylor, A; Durbaba, R; Rodgers, J F

    1992-10-01

    1. The effects of the muscle-depolarizing drug succinylcholine (SCh) on the stretch responses of jaw-closer muscle spindle afferents were studied in the anaesthetized cat. Using ramp and hold stretches repeated every 6 s the basic measurements made were: initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Derived from these were: dynamic difference (DD) = PF-IF, dynamic index (DI) = PF-SI and static difference (SD) = SI-IF. Increases in these measures caused by a single I.V. dose of SCh (200 micrograms kg-1) are symbolized by the prefix delta. 2. In a population of 234 units, delta DD and delta IF were each distributed bimodally, but were uncorrelated, thus defining four subgroups. 3. delta DD was argued to be an index of the effect of bag1 intrafusal fibre contraction and delta IF to be an index of the effect of bag2 fibre contraction. On this basis it is proposed that units can be divided into four groups according to the predominant influences of the bag1, bag2 and chain fibres as b1c (6.8%), b1b2c (22.2%), b2c (54.3%) or c (16.7%). 4. Testing with sine wave stretches at 1 Hz showed that changes in mean frequency and amplitude of response caused by SCh correlated with delta IF and delta DD respectively, but separated groups of units much less effectively than did ramp and hold testing. 5. Evidence is presented to indicate that the control value of DD in passive spindles does not relate to the potential strength of bag1 fibre effects in fully activated spindles. The bag1 fibre appears to contribute little to responses of spindle afferents in the passive state. DD is superior to DI as a measure of bag1 effects. 6. Conduction velocity was unimodally distributed in masseter spindle afferents and was not correlated with delta DD or delta IF and was therefore of no value in classifying them. 7. Neither the threshold of afferents to quick transient stretch nor the coefficient of variation of

  6. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  7. 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.

  8. 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

  9. Cardiac Sympathetic Afferent Denervation Attenuates Cardiac Remodeling and Improves Cardiovascular Dysfunction in Rats with Heart Failure

    PubMed Central

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G.; Rozanski, George J.; Zucker, Irving H.

    2014-01-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympatho-excitation in chronic heart failure (CHF). Increased sympatho-excitation is positively related to mortality in CHF patients. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. In order to selectively delete the transient receptor potential vanilloid 1 receptor (TRPV1) -expressing CSAR afferents, epicardial application of resiniferatoxin (RTX, 50 μg/ml), an ultrapotent analogue of capsaicin, was performed during myocardium infarction (MI) surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of RTX largely prevented the elevated LVEDP, lung edema and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that RTX attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and TGF β-receptor I in CHF rats. Pressure - volume loop analysis showed that RTX reduced the end diastolic pressure volume relations in CHF rats indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. PMID:24980663

  10. Long lasting activity of nociceptive muscular afferents facilitates bilateral flexion reflex pattern in the feline spinal cord.

    PubMed

    Schomburg, E D; Steffens, H; Pilyavskii, A I; Maisky, V A; Brück, W; Dibaj, P; Sears, T A

    2015-06-01

    Chronic muscular limb pain requires the adoption of motor patterns distinct from the classic ipsilateral flexion, crossed extension and corresponding reciprocal inhibitions to acute exteroceptive stimulation. Using selective chemical activation of group III/IV afferents in gastrocnemius-soleus (GS) muscles we investigated bilaterally their reflex responses conditioned by (a) acute 'myositis' induced by intramuscular carrageenan; and (b) sub-acute 'myositis' induced by infusion of complete Freund's adjuvant (CFA). Reflex transmission was detected by monosynaptic testing and c-fos staining used to identify increased neuronal activity. In all control experiments with chemical stimulation of group III/IV afferents, ipsilateral responses conformed to the flexor reflex pattern. However, the expected contralateral facilitation of GS motoneurones occurred in fewer than 50% trials while only 9% of trials induced contralateral inhibition of flexor posterior-biceps-semitendinosus (PBSt) motoneurones. During carrageenan acute myositis contralateral PBSt was transiently facilitated by selective activation of group III/IV afferents. During CFA-induced myositis, contralateral only inhibition of GS motoneurones occurred instead of any facilitation, while bidirectionally a crossed facilitation of PBST dominated. These reflex changes were mirrored in an enhanced number of neurones with enhanced c-fos expression. Muscle pain, particularly if chronically persistent, requires another behavioural response pattern than acute exteroceptive pain.

  11. Thresholds of cutaneous afferents related to perceptual threshold across the human foot sole.

    PubMed

    Strzalkowski, Nicholas D J; Mildren, Robyn L; Bent, Leah R

    2015-10-01

    Perceptual thresholds are known to vary across the foot sole, despite a reported even distribution in cutaneous afferents. Skin mechanical properties have been proposed to account for these differences; however, a direct relationship between foot sole afferent firing, perceptual threshold, and skin mechanical properties has not been previously investigated. Using the technique of microneurography, we recorded the monofilament firing thresholds of cutaneous afferents and associated perceptual thresholds across the foot sole. In addition, receptive field hardness measurements were taken to investigate the influence of skin hardness on these threshold measures. Afferents were identified as fast adapting [FAI (n = 48) or FAII (n = 13)] or slowly adapting [SAI (n = 21) or SAII (n = 20)], and were grouped based on receptive field location (heel, arch, metatarsals, toes). Overall, perceptual thresholds were found to most closely align with firing thresholds of FA afferents. In contrast, SAI and SAII afferent firing thresholds were found to be significantly higher than perceptual thresholds and are not thought to mediate monofilament perceptual threshold across the foot sole. Perceptual thresholds and FAI afferent firing thresholds were significantly lower in the arch compared with other regions, and skin hardness was found to positively correlate with both FAI and FAII afferent firing and perceptual thresholds. These data support a perceptual influence of skin hardness, which is likely the result of elevated FA afferent firing threshold at harder foot sole sites. The close coupling between FA afferent firing and perceptual threshold across foot sole indicates that small changes in FA afferent firing can influence perceptual thresholds.

  12. Voltage-gated Na(+) channels in chemoreceptor afferent neurons--potential roles and changes with development.

    PubMed

    Donnelly, David F

    2013-01-01

    Carotid body chemoreceptors increase their action potential (AP) activity in response to a decrease in arterial oxygen tension and this response increases in the post-natal period. The initial transduction site is likely the glomus cell which responds to hypoxia with an increase in intracellular calcium and secretion of multiple neurotransmitters. Translation of this secretion to AP spiking levels is determined by the excitability of the afferent nerve terminals that is largely determined by the voltage-dependence of activation of Na(+) channels. In this review, we examine the biophysical characteristics of Na(+) channels present at the soma of chemoreceptor afferent neurons with the assumption that similar channels are present at nerve terminals. The voltage dependence of this current is consistent with a single Na(+) channel isoform with activation around the resting potential and with about 60-70% of channels in the inactive state around the resting potential. Channel openings, due to transitions from inactive/open or closed/open states, may serve to amplify external depolarizing events or generate, by themselves, APs. Over the first two post-natal weeks, the Na(+) channel activation voltage shifts to more negative potentials, thus enhancing the amplifying action of Na(+) channels on depolarization events and increasing membrane noise generated by channel transitions. This may be a significant contributor to maturation of chemoreceptor activity in the post-natal period.

  13. 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

  14. 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

  15. 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

  16. Functional specificity of rat vibrissal primary afferents.

    PubMed

    Lucianna, Facundo A; Farfán, Fernando D; Pizá, Gabriel A; Albarracín, Ana L; Felice, Carmelo J

    2016-06-01

    In this study, we propose to analyze the peripheral vibrissal system specificity through its neuronal responses. Receiver operating characteristics (ROC) curve analyses were used, which required the implementation of a binary classifier (artificial neural network) trained to identify the applied stimulus. The training phase consisted of the observation of a predetermined amount of vibrissal sweeps on two surfaces of different texture and similar roughness. Our results suggest that the specificity of the peripheral vibrissal system easily permits the discrimination between perceived stimuli, quantified through neuronal responses, and that it can be evaluated through an ROC curve analysis. We found that such specificity makes a linear binary classifier capable of detecting differences between stimuli with five sweeps at most.

  17. Characterization of primary afferent spinal innervation of mouse uterus.

    PubMed

    Herweijer, Geraldine; Kyloh, Melinda; Beckett, Elizabeth A H; Dodds, Kelsi N; Spencer, Nick J

    2014-01-01

    The primary afferent innervation of the uterus is incompletely understood. The aim of this study was to identify the location and characteristics of primary afferent neurons that innervate the uterine horn of mice and correlate the different morphological types of putative primary afferent nerve endings, immunoreactive to the sensory marker, calcitonin gene related peptide (CGRP). Using retrograde tracing, injection of 5-10 μL of 1,1'-didodecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate (DiI) into discrete single sites in each uterine horn revealed a biomodal distribution of sensory neurons in dorsal root ganglia (DRG) with peak labeling occurring between T13-L3 and a second smaller peak between L6-S1. The mean cross sectional area of labeled cells was 463 μm(2) ± s.e.m. A significantly greater proportion of labeled neurons consisted of small cell bodies (<300 μm(2)) in the sacral spinal cord (S2) compared with peak labeling at the lumbar (L2) region. In both sections and whole mount preparations, immunohistochemical staining for CGRP revealed substantial innervation of the uterus by CGRP-positive nerve fibers located primarily at the border between the circular and longitudinal muscle layers (N = 4). The nerve endings were classified into three distinct types: "single," "branching," or "complex," that often aligned preferentially in either the circular or longitudinal axis of the smooth muscles. Complex endings were often associated with mesenteric vessels. We have identified that the cell bodies of primary afferent neurons innervating the mouse uterus lie primarily in DRG at L2 and S1 spinal levels. Also, the greatest density of CGRP immunoreactivity lies within the myometrium, with at least three different morphological types of nerve endings identified. These findings will facilitate further investigations into the mechanisms underlying sensory transduction in mouse uterus. PMID:25120416

  18. Coding of stimuli by ampullary afferents in Gnathonemus petersii.

    PubMed

    Engelmann, J; Gertz, S; Goulet, J; Schuh, A; von der Emde, G

    2010-10-01

    Weakly electric fish use electroreception for both active and passive electrolocation and for electrocommunication. While both active and passive electrolocation systems are prominent in weakly electric Mormyriform fishes, knowledge of their passive electrolocation ability is still scarce. To better estimate the contribution of passive electric sensing to the orientation toward electric stimuli in weakly electric fishes, we investigated frequency tuning applying classical input-output characterization and stimulus reconstruction methods to reveal the encoding capabilities of ampullary receptor afferents. Ampullary receptor afferents were most sensitive (threshold: 40 μV/cm) at low frequencies (<10 Hz) and appear to be tuned to a mix of amplitude and slope of the input signals. The low-frequency tuning was corroborated by behavioral experiments, but behavioral thresholds were one order of magnitude higher. The integration of simultaneously recorded afferents of similar frequency-tuning resulted in strongly enhanced signal-to-noise ratios and increased mutual information rates but did not increase the range of frequencies detectable by the system. Theoretically the neuronal integration of input from receptors experiencing opposite polarities of a stimulus (left and right side of the fish) was shown to enhance encoding of such stimuli, including an increase of bandwidth. Covariance and coherence analysis showed that spiking of ampullary afferents is sufficiently explained by the spike-triggered average, i.e., receptors respond to a single linear feature of the stimulus. Our data support the notion of a division of labor of the active and passive electrosensory systems in weakly electric fishes based on frequency tuning. Future experiments will address the role of central convergence of ampullary input that we expect to lead to higher sensitivity and encoding power of the system. PMID:20685928

  19. Neuropathic pain: Early spontaneous afferent activity is the trigger

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Meij, Johanna T.A.; Zhang, Jun-Ming; Yu, Lei

    2005-01-01

    Intractable neuropathic pain often results from nerve injury. One immediate event in damaged nerve is a sustained increase in spontaneous afferent activity, which has a well-established role in ongoing pain. Using two rat models of neuropathic pain, the CCI and SNI models, we show that local, temporary nerve blockade of this afferent activity permanently inhibits the subsequent development of both thermal hyperalgesia and mechanical allodynia. Timing is critical—the nerve blockade must last at least 3–5 days and is effective if started immediately after nerve injury, but not if started at 10 days after injury when neuropathic pain is already established. Effective nerve blockade also prevents subsequent development of spontaneous afferent activity measured electrophysiologically. Similar results were obtained in both pain models, and with two blockade methods (200 mg of a depot form bupivacaine at the injury site, or perfusion of the injured nerve just proximal to the injury site with TTX). These results indicate that early spontaneous afferent fiber activity is the key trigger for the development of pain behaviors, and suggest that spontaneous activity may be required for many of the later changes in the sensory neurons, spinal cord, and brain observed in neuropathic pain models. Many pre-clinical and clinical studies of pre-emptive analgesia have used much shorter duration of blockade, or have not started immediately after the injury. Our results suggest that effective pre-emptive analgesia can be achieved only when nerve block is administered early after injury and lasts several days. PMID:15964687

  20. 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.

  1. 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

  2. Putative roles of neuropeptides in vagal afferent signaling

    PubMed Central

    de Lartigue, Guillaume

    2014-01-01

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

  3. 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

  4. Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension.

    PubMed

    Chen, W-W; Xiong, X-Q; Chen, Q; Li, Y-H; Kang, Y-M; Zhu, G-Q

    2015-04-01

    Persistent excessive sympathetic activation greatly contributes to the pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex with positive feedback characteristics. Humoral factors such as bradykinin, adenosine and reactive oxygen species produced in myocardium due to myocardial ischaemia stimulate cardiac sympathetic afferents and thereby reflexly increase sympathetic activity and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and hypertension. The enhanced CSAR at least partially contributes to the sympathetic activation and pathogenesis of these diseases. Nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla are the most important central sites involved in the modulation and integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase-derived superoxide anions pathway in the PVN are mainly responsible for the enhanced CSAR in CHF and hypertension. Central angiotensin-(1-7), nitric oxide, endothelin, intermedin, hydrogen peroxide and several other signal molecules are involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF and hypertension. This review focuses on the anatomical and physiological basis of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the role of enhanced CSAR in the pathogenesis of CHF and hypertension.

  5. Intact cutaneous C fibre afferent properties in mechanical and cold neuropathic allodynia

    PubMed Central

    Hulse, Richard; Wynick, David; Donaldson, Lucy F.

    2010-01-01

    Patients with neuropathy, report changes in sensory perception, particularly mechanical and thermal allodynia, and spontaneous pain. Similar sensory changes are seen in experimental neuropathies, in which alteration in primary afferent properties can also be determined. The neural correlate of spontaneous pain is ongoing activity in sensory afferents. Mechanical and heat allodynia are thought to result from lowered activation thresholds in primary afferent and/or central neurones, but the mechanisms underlying cold allodynia are very poorly understood. We investigated nociceptive behaviours and the properties of C and A fibre intact afferents running adjacent to damaged afferents following a partial ligation injury of the saphenous nerve (PSNI). Animals developed mechanical and cold allodynia by 3 days after PSNI. Intact mechanosensitive C fibre afferents developed ongoing activity, and had slower conduction velocities 3 and 7 days following nerve injury, with no change in mechanical threshold. There was a large increase (∼46-fold) in calculated afferent input 3 days after nerve injury, as a result of the ongoing activity in these fibres. Mechano-cooling-sensitive C fibre afferents showed both enhanced cooling-evoked firing, and increased ongoing activity. The afferent barrage associated with mechano-cooling-sensitive afferents was increased 26-fold 7 days after nerve injury. We observed no differences in the properties of intact A fibre mechanosensitive afferents. These studies demonstrate for the first time that the altered nociception seen after PSNI is associated with ongoing activity and enhanced cooling-evoked activity in intact C fibre afferents in the saphenous nerve, with no concurrent alteration in A fibre afferents. PMID:19942464

  6. 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.

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

    PubMed

    Wu, An; Dvoryanchikov, Gennady; Pereira, Elizabeth; Chaudhari, Nirupa; Roper, Stephen D

    2015-09-16

    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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

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

    PubMed

    Wang, Z-Y; McDowell, T; Wang, P; Alvarez, R; Gomez, T; Bjorling, D E

    2014-09-26

    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 (100ng/ml) for 30 min significantly increased the number of neurons that responded to capsaicin (as indicated by increased intracellular Ca(2 +) concentration). Pretreatment with the CB1 agonist ACEA (10nM) 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.

  13. 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

  14. 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

  15. The effect of succinylcholine on cat gastrocnemius muscle spindle afferents of different types.

    PubMed

    Taylor, A; Rodgers, J F; Fowle, A J; Durbaba, R

    1992-10-01

    1. A population of 269 gastrocnemius muscle spindle afferents have been studied in anaesthetized cats for the effects of succinylcholine (SCh) on their response to ramp and hold stretches repeated every 6 s. The effectiveness and reliability of the SCh test was improved by prior stimulation of the muscle at 10 Hz for 30 s to increase the blood flow. 2. Responses have been assessed from averaged cycle histograms before and after a single I.V. dose of SCh of 200 micrograms kg-1. As for previous studies of jaw muscle spindles the basic measurements were initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Dynamic difference (DD = PF-IF), dynamic index (DI = PF-SI) and static difference (SD = SI-IF) were derived from these and increases caused by SCh indicated by the prefix delta. 3. delta DD and delta IF were each distributed bimodally and since they were uncorrelated formed the basis for a four-way classification. Since delta DD can be attributed to activation of bag1 (b1) intrafusal fibres and delta IF to bag2 (b2) fibres, while all afferents receive input from chain (c) fibres it is proposed as with the jaw spindles that the classes correspond to predominant influence from b1c, b1b2c, b2c and c intrafusal fibres. 4. The proportion of units in the different groups were similar to those in the jaw muscles except for there being very few b1c type in gastrocnemius. 5. Conduction velocity was bimodally distributed with the best dividing line at 63.2 m s-1. The b1b2c units were all, save one, in the fast group, while the b2c units were equally divided between fast and slow. 6. Mean control values for DD did not differ between the b1b2c and the b2c groups, which is taken to indicate that the b1 fibre does not contribute significantly to the dynamic stretch response of spindles with no intrafusal contraction. 7. The results emphasize the importance of recognizing that some apparently primary afferents

  16. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla.

    PubMed

    Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E; Carey, John P

    2005-02-01

    Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P < 0.001) on the treated side (early: 44.3 +/- 16.3; late: 33.9 +/- 13.2 spikes x s(-1)) than on the untreated side (54.9 +/- 16.8 spikes x s(-1)). Spontaneous rates of irregular and intermediate afferents did not change. The majority of treated afferents did not measurably respond to tilt or rotation (82% in the early group, 76% in the late group). Those that did respond had abnormally low sensitivities (P < 0.001). Treated canal units that responded to rotation had mean sensitivities only 5-7% of the values for untreated canal afferents. Treated otolith afferents had mean sensitivities 23-28% of the values for untreated otolith units. Sensitivity to externally applied galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

  17. 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

  18. 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

  19. 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.

  20. Mechanosensory transduction of vagal and baroreceptor afferents revealed by study of isolated nodose neurons in culture.

    PubMed

    Snitsarev, Vladislav; Whiteis, Carol A; Abboud, Francois M; Chapleau, Mark W

    2002-06-28

    Changes in arterial pressure and blood volume are sensed by baroreceptor and vagal afferent nerves innervating aorta and heart with soma in nodose ganglia. The inability to measure membrane potential at the nerve terminals has limited our understanding of mechanosensory transduction. Goals of the present study were to: (1) Characterize membrane potential and action potential responses to mechanical stimulation of isolated nodose sensory neurons in culture; and (2) Determine whether the degenerin/epithelial sodium channel (DEG/ENaC) blocker amiloride selectively blocks mechanically induced depolarization without suppressing membrane excitability. Membrane potential of isolated rat nodose neurons was measured with sharp microelectrodes. Mechanical stimulation with buffer ejected from a micropipette (5, 10, 20 psi) depolarized 6 of 10 nodose neurons (60%) in an intensity-dependent manner. The depolarization evoked action potentials in 4 of the 6 neurons. Amiloride (1 microM) essentially abolished mechanically induced depolarization (15 +/- 4 mV during control vs. 1 +/- 2 mV during amiloride with 20-psi stimulation, n = 6) and action potential discharge. In contrast, amiloride did not inhibit the frequency of action potential discharge in response to depolarizing current injection (n = 6). In summary, mechanical stimulation depolarizes and triggers action potentials in a subpopulation of nodose sensory neurons in culture. The DEG/ENaC blocker amiloride at a concentration of 1 microM inhibits responses to mechanical stimulation without suppressing membrane excitability. The results support the hypothesis that DEG/ENaC subunits are components of mechanosensitive ion channels on vagal afferent and baroreceptor neurons. PMID:12144042

  1. Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

    PubMed

    Xu, Bo; Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

    2015-05-01

    Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-D-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure.

  2. Meningeal afferent signaling and the pathophysiology of migraine.

    PubMed

    Burgos-Vega, Carolina; Moy, Jamie; Dussor, Gregory

    2015-01-01

    Migraine is the most common neurological disorder. Attacks are complex and consist of multiple phases but are most commonly characterized by intense, unilateral, throbbing headache. The pathophysiology contributing to migraine is poorly understood and the disorder is not well managed with currently available therapeutics, often rendering patients disabled during attacks. The mechanisms most likely to contribute to the pain phase of migraine require activation of trigeminal afferent signaling from the cranial meninges and subsequent relay of nociceptive information into the central nervous system in a region of the dorsal brainstem known as the trigeminal nucleus caudalis. Events leading to activation of meningeal afferents are unclear, but nerve endings within this tissue are mechanosensitive and also express a variety of ion channels including acid-sensing ion channels and transient receptor-potential channels. These properties may provide clues into the pathophysiology of migraine by suggesting that decreased extracellular pH and environmental irritant exposure in the meninges contributes to headache. Neuroplasticity is also likely to play a role in migraine given that attacks are triggered by routine events that are typically nonnoxious in healthy patients and clear evidence of sensitization occurs during an attack. Where and how plasticity develops is also not clear but may include events directly on the afferents and/or within the TNC. Among the mediators potentially contributing to plasticity, calcitonin gene-related peptide has received the most attention within the migraine field but other mechanisms may also contribute. Ultimately, greater understanding of the molecules and mechanisms contributing to migraine will undoubtedly lead to better therapeutics and relief for the large number of patients across the globe who suffer from this highly disabling neurological disorder.

  3. 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

  4. Evidence for the participation of glutamate in reflexes involving afferent, substance P-containing nerve fibres in the rat.

    PubMed

    Juránek, I; Lembeck, F

    1996-01-01

    1. Responses mediated, either peripherally or centrally, by substance P-containing primary afferent C-fibres were investigated in the rat following impairment of axonal transport by colchicine (120 micrograms kg-1, i.p., daily for 3 days), and after treatment with the tachykinin antagonist SR-140333 (10-100 micrograms kg-1, i.v.) or the N-methyl-D-aspartate (NMDA) antagonist MK-801 (100 micrograms kg-1). 2. Peripheral effects mediated by afferent C-fibres were measured by plasma protein extravasation (Evans blue method), following antidromic stimulation of the sciatic nerve, topical application of mustard oil and, as control, i.v. injection of substance P. SR-140333 (100 micrograms kg-1) reduced the effects by 86%, 75% and 74%, respectively. Colchicine reduced the effects of the first two stimuli by 31% and 33% and, as expected not the effect of substance P. The increase of paw skin temperature following capsaicin i.v. was inhibited by SR-140333, but not by colchicine. MK-801 had no effect on the plasma protein extravasation following antidromic sciatic nerve stimulation or on the rise of paw skin temperature induced by capsaicin i.v., thus excluding an effect of MK-801 on peripheral terminals of afferent neurones. 3. Depressor reflexes, which are known to be mediated by capsaicin-sensitive afferent neuones, such as those elicited (A) by a stimulating dose of 30 ng capsaicin i.a., (B) by distension of the ascending colon or (C) by afferent sciatic nerve stimulation were studied. Colchicine significantly reduced depressor reflexes A and B, but had no effect on reflex C. None of the reflexes was affected by SR-140333. MK-801 significantly inhibited all three reflexes. 4. Capsaicin, injected either i.v. (200 micrograms kg-1) or into the nucleus caudatus/putamen (i.c., 30 micrograms), induced an increase in paw skin temperature and a decrease in colon temperature. The rise in fore paw skin temperature (delta t = 2.3 +/- 0.4 degrees C) evoked by capsaicin i.v. was

  5. Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents.

    PubMed

    Patacchini, R; Maggi, C A; Meli, A

    1990-07-01

    1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mumol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acrylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals.

  6. The role of resting frontal EEG asymmetry in psychopathology: afferent or efferent filter?

    PubMed

    Gatzke-Kopp, Lisa M; Jetha, Michelle K; Segalowitz, Sidney J

    2014-01-01

    Resting EEG asymmetry evident early in life is thought to bias affective behaviors and contribute to the development of psychopathology. However, it remains unclear at what stage of information processing this bias occurs. Asymmetry may serve as an afferent filter, modulating emotional reactivity to incoming stimuli; or as an efferent filter, modulating behavioral response tendencies under emotional conditions. This study examines 209 kindergarten children (M = 6.03 years old) to test predictions put forth by the two models. Resting asymmetry was examined in conjunction with electrodermal and cardiac measures of physiological reactivity to four emotion-inducing film clips (fear, sad, happy, anger) and teacher ratings of psychopathology. Results confirm an association between increased right side cortical activation and internalizing symptom severity as well as left activation and externalizing symptom severity. Significant interactions between resting asymmetry and physiological reactivity to emotion indicate that physiological reactivity moderates the association between resting asymmetry and symptoms of psychopathology.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. [Muscle afferent block for the treatment of writer's cramp].

    PubMed

    Sawamoto, N; Kaji, R; Katayama, M; Kubori, T; Kimura, J

    1995-11-01

    A 29-year-old man suffered from dystonic writer's cramp for over three years. When he wrote, typed and did other tasks using right hand, dystonic involuntary movement triggered medial rotation of the arm, wrist extension and shoulder elevation. Medication, biofeedback, and botulinum injection were performed without much success. We tried to block the sensory input from muscles by using lidocaine and ethanol. We made injections of 0.5% lidocaine 50ml and 99% ethanol 5ml into muscles with abnormal activity at the frequency of twice a week for about six months. After the treatment, dystonic movement was remarkably improved and he was then able to write, type and perform other tasks with the right hand. Side effects included pain of the injection site, nausea and dizziness, which lasted for a few hours. This "muscle afferent block" did not cause muscle weakness. We speculate that muscle afferent plays a pivotal role in dystonia so that its blocking may be of clinical use.

  13. Spontaneous hyperactivity in the auditory midbrain: relationship to afferent input.

    PubMed

    Robertson, Donald; Bester, Christofer; Vogler, Darryl; Mulders, Wilhelmina H A M

    2013-01-01

    Hyperactivity in the form of increased spontaneous firing rates of single neurons develops in the guinea pig inferior colliculus (IC) after unilateral loud sound exposures that result in behavioural signs of tinnitus. The hyperactivity is found in those parts of the topographic frequency map in the IC where neurons possess characteristic frequencies (CFs) closely related to the region in the cochlea where lasting sensitivity changes occur as a result of the loud sound exposure. The observed hyperactivity could be endogenous to the IC, or it could be driven by hyperactivity at lower stages of the auditory pathway. In addition to the dorsal cochlear nucleus (DCN) hyperactivity reported by others, specific cell types in the ventral cochlear nucleus (VCN) also show hyperactivity in this animal model suggesting that increased drive from several regions of the lower brainstem could contribute to the observed hyperactivity in the midbrain. In addition, spontaneous afferent drive from the cochlea itself is necessary for the maintenance of hyperactivity up to about 8 weeks post cochlear trauma. After 8 weeks however, IC hyperactivity becomes less dependent on cochlear input, suggesting that central neurons transition from a state of hyperexcitability to a state in which they generate their own endogenous firing. The results suggest that there might be a "therapeutic window" for early-onset tinnitus, using treatments that reduce cochlear afferent firing. PMID:22349094

  14. 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

  15. 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

  16. 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

  17. 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.

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

    PubMed

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B; Kaufmann, Horacio

    2011-11-01

    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

  19. Neonatal inflammation and primary afferent terminal plasticity in the rat dorsal horn.

    PubMed

    Walker, Suellen M; Meredith-Middleton, Jacqueta; Cooke-Yarborough, Claire; Fitzgerald, Maria

    2003-09-01

    Abnormal or excessive activity related to pain and injury in early life may alter normal synaptic development and lead to changes in somatosensory processing. The aim of the current study was to define the critical factors that determine long-term plasticity in spinal cord afferent terminals following neonatal inflammation. Hindpaw inflammation was produced in neonatal rat pups with 5 or 25 microl 2% carrageenan, and 5 or 25 microl complete Freund's adjuvant (CFA). All groups displayed a clear inflammatory response that recovered in 2 weeks in all but the 25 microl CFA group, who had persistent chronic inflammation confirmed by histological examination of the paw at 8 weeks. The 25 microl CFA group was also the only group that displayed a significant expansion of the sciatic and saphenous nerve terminal field in lamina II of the dorsal horn at 8 weeks, using wheat-germ agglutinin-horse radish peroxidase transganglionic labelling. This effect was not accompanied by changes in dorsal root ganglion (DRG) cell number, expression of activating transcription factor 3 (ATF3), or alterations in calcitonin gene related peptide (CGRP) or isolectin B4 binding; and was not mimicked by partial nerve damage. No long-term change in mechanical or thermal behavioural sensory thresholds was seen in any group. Lower dose CFA caused an acute, reversible expansion of terminal fields in lamina II in neonatal animals, while CFA did not produce this effect in adults. The duration and effect of neonatal inflammation is therefore dependent on the type and volume of inflammatory agent used. The expansion of afferent terminals in lamina II following neonatal CFA inflammation is maintained into adulthood if the inflammation is also maintained, as seen following 25 microl CFA. This effect is not seen in adult animals, emphasising the plasticity of the nervous system early in development.

  20. 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.

  1. 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

  2. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.

    PubMed

    Wild, Vanessa; Messlinger, Karl; Fischer, Michael J M

    2015-08-18

    Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.

  3. Fos activation of selective afferents to ventral tegmental area during cue-induced reinstatement of cocaine seeking in rats.

    PubMed

    Mahler, Stephen V; Aston-Jones, Gary S

    2012-09-19

    Ventral tegmental area (VTA) dopamine neurons are crucial for appetitive responses to Pavlovian cues, including cue-induced reinstatement of drug seeking. However, it is unknown which VTA inputs help activate these neurons, transducing stimuli into salient cues that drive drug-seeking behavior. Here we examined 56 VTA afferents from forebrain and midbrain that are Fos activated during cue-induced reinstatement. We injected the retrograde tracer cholera toxin β subunit (CTb) unilaterally into rostral or caudal VTA of male rats. All animals were trained to self-administer cocaine, then extinguished of this behavior. On a final test day, animals were exposed to response-contingent cocaine-associated cues, extinction conditions, a non-cocaine-predictive CS-, or a novel environment, and brains were processed to visualize CTb and Fos immunoreactivity to identify VTA afferents activated in relation to behaviors. VTA-projecting neurons in subregions of medial accumbens shell, ventral pallidum, elements of extended amygdala, and lateral septum (but not prefrontal cortex) were activated specifically during cue-induced cocaine seeking, and some of these were also activated proportionately to the degree of cocaine seeking. Surprisingly, though efferents from the lateral hypothalamic orexin field were also Fos activated during reinstatement, these were largely non-orexinergic. Also, VTA afferents from the rostromedial tegmental nucleus and lateral habenula were specifically activated during extinction and CS- tests, when cocaine was not expected. These findings point to a select set of subcortical nuclei which provide reinstatement-related inputs to VTA, translating conditioned stimuli into cocaine-seeking behavior.

  4. Puptrak 1.0--a new semiautomated system for pupillometry with the Octopus perimeter: a preliminary report.

    PubMed

    Fankhauser, F; Flammer, J

    1989-11-01

    A provisional, semiautomated version of a system for automated testing of the afferent pupillary reflex with perimetric methods under controlled conditions is described. The target projected onto the perimeter cupola is used as the stimulus for triggering the pupillary response. In a modification to the Octopus 201, the pupil is illuminated by two IR LED diodes, while the pupillary responses are recorded by the onboard IR sensitive TV camera built into the perimetric unit. Measurements of the pupillary area as a function of time and stimulus luminance have been performed and have resulted in consistent results. Here, one perimetric program, working with stimuli above the threshold for the afferent pupillary light reflex is described. The present setup works with system-specific software and standard hardware, the central data processing unit being a desk-top computer (IBM PC AT-03). The mating of an automated pupillary measuring unit to an automated perimeter may open the door for a more widespread evaluation of the value and the clinical application range of pupillary perimetry and may be of interest in other areas of visual and clinical psychophysics. The shortcomings of the present system, in particular insufficient temporal resolution and lack of full automation, are being removed at the present time.

  5. 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)

  6. 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.

  7. Organization of afferents to the striatopallidal systems in the fire-bellied toad Bombina orientalis.

    PubMed

    Ramsay, Zachary J; Laberge, Frédéric

    2014-11-01

    The cerebral hemispheres of amphibians display paired dorsal and ventral striatum (commonly referred to as striatum proper and nucleus accumbens, respectively). Each striatal region is proposed to be closely associated with a pallidal structure located caudal to it to form a striatopallidal system. In the present study, afferents to the dorsal and ventral striatopallidal systems of the fire-bellied toad (Bombina orientalis) were investigated using the neuronal tracer biocytin. A quantitative analysis of the topographical distribution of afferent neurons from the thalamus and posterior tubercle/ventral tegmentum was emphasised. The main results show that inputs to the two striatopallidal systems originate from distinct dorsal thalamic nuclei, with dorsal and ventral striatopallidal afferent neurons favouring strongly the lateral/central and anterior thalamic nuclei, respectively. However, afferent neuron distribution in the dorsal thalamus does not differ in the rostrocaudal axis of the brain. Afferent neurons from the posterior tubercle and ventral tegmentum, on the other hand, are organised topographically along the rostrocaudal axis. About 85 % of afferent neurons to the dorsal striatopallidal system are located rostrally in the posterior tubercle, while 75 % of afferent neurons to the ventral striatopallidal system are found more caudally in the ventral tegmentum. This difference is statistically significant and confirms the presence of distinct mesostriatal pathways in an amphibian. These findings demonstrate that an amphibian brain displays striatopallidal systems integrating parallel streams of sensory information potentially under the influence of distinct ascending mesostriatal pathways.

  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. 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.

  10. Afferent Input Selects NMDA Receptor Subtype to Determine the Persistency of Hippocampal LTP in Freely Behaving Mice

    PubMed Central

    Ballesteros, Jesús J.; Buschler, Arne; Köhr, Georg; Manahan-Vaughan, Denise

    2016-01-01

    The glutamatergic N-methyl-D-aspartate receptor (NMDAR) is critically involved in many forms of hippocampus-dependent memory that may be enabled by synaptic plasticity. Behavioral studies with NMDAR antagonists and NMDAR subunit (GluN2) mutants revealed distinct contributions from GluN2A- and GluN2B-containing NMDARs to rapidly and slowly acquired memory performance. Furthermore, studies of synaptic plasticity, in genetically modified mice in vitro, suggest that GluN2A and GluN2B may contribute in different ways to the induction and longevity of synaptic plasticity. In contrast to the hippocampal slice preparation, in behaving mice, the afferent frequencies that induce synaptic plasticity are very restricted and specific. In fact, it is the stimulus pattern and not variations in afferent frequency that determine the longevity of long-term potentiation (LTP) in vivo. Here, we explored the contribution of GluN2A and GluN2B to LTP of differing magnitudes and persistence in freely behaving mice. We applied differing high-frequency stimulation (HFS) patterns at 100 Hz to the hippocampal CA1 region, to induce NMDAR-dependent LTP in wild-type (WT) mice, that endured for <1 h (early (E)-LTP), (LTP, 2–4 h) or >24 h (late (L)-LTP). In GluN2A-knockout (KO) mice, E-LTP (HFS, 50 pulses) was significantly reduced in magnitude and duration, whereas LTP (HFS, 2 × 50 pulses) and L-LTP (HFS, 4 × 50 pulses) were unaffected compared to responses in WT animals. By contrast, pharmacological antagonism of GluN2B in WT had no effect on E-LTP but significantly prevented LTP. E-LTP and LTP were significantly impaired by GluN2B antagonism in GluN2A-KO mice. These data indicate that the pattern of afferent stimulation is decisive for the recruitment of distinct GluN2A and GluN2B signaling pathways that in turn determine the persistency of hippocampal LTP. Whereas brief bursts of patterned stimulation preferentially recruit GluN2A and lead to weak and short-lived forms of LTP, prolonged

  11. Electrical stimulation of low-threshold afferent fibers induces a prolonged synaptic depression in lamina II dorsal horn neurons to high-threshold afferent inputs in mice.

    PubMed

    Sdrulla, Andrei D; Xu, Qian; He, Shao-Qiu; Tiwari, Vinod; Yang, Fei; Zhang, Chen; Shu, Bin; Shechter, Ronen; Raja, Srinivasa N; Wang, Yun; Dong, Xinzhong; Guan, Yun

    2015-06-01

    Electrical stimulation of low-threshold Aβ-fibers (Aβ-ES) is used clinically to treat neuropathic pain conditions that are refractory to pharmacotherapy. However, it is unclear how Aβ-ES modulates synaptic responses to high-threshold afferent inputs (C-, Aδ-fibers) in superficial dorsal horn. Substantia gelatinosa (SG) (lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. We recorded C-fiber-evoked excitatory postsynaptic currents (eEPSCs) in spinal cord slices in response to paired-pulse test stimulation (500 μA, 0.1 millisecond, 400 milliseconds apart). We showed that 50-Hz and 1000-Hz, but not 4-Hz, Aβ-ES (10 μA, 0.1 millisecond, 5 minutes) induced prolonged inhibition of C-fiber eEPSCs in SG neurons in naive mice. Furthermore, 50-Hz Aβ-ES inhibited both monosynaptic and polysynaptic forms of C-fiber eEPSC in naive mice and mice that had undergone spinal nerve ligation (SNL). The paired-pulse ratio (amplitude second eEPSC/first eEPSC) increased only in naive mice after 50-Hz Aβ-ES, suggesting that Aβ-ES may inhibit SG neurons by different mechanisms under naive and nerve-injured conditions. Finally, 50-Hz Aβ-ES inhibited both glutamatergic excitatory and GABAergic inhibitory interneurons, which were identified by fluorescence in vGlut2-Td and glutamic acid decarboxylase-green fluorescent protein transgenic mice after SNL. These findings show that activities in Aβ-fibers lead to frequency-dependent depression of synaptic transmission in SG neurons in response to peripheral noxious inputs. However, 50-Hz Aβ-ES failed to induce cell-type-selective inhibition in SG neurons. The physiologic implication of this novel form of synaptic depression for pain modulation by Aβ-ES warrants further investigation. PMID:25974163

  12. 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

  13. Distribution of input and output synapses on the central branches of bushcricket and cricket auditory afferent neurones: immunocytochemical evidence for GABA and glutamate in different populations of presynaptic boutons.

    PubMed

    Hardt, M; Watson, A H

    1999-01-18

    In order to investigate the synapses on the terminals of primary auditory afferents in the bushcricket and cricket, these were impaled with microelectrodes and after physiological characterisation, injected intracellularly with horseradish peroxidase. The tissue was prepared for electron microscopy, and immunocytochemistry for gamma-aminobutyric acid (GABA) and glutamate was carried out on ultrathin sections by using a post-embedding immunogold technique. The afferent terminals received many input synapses. Between 60-65% of these were made by processes immunoreactive for GABA and approximately 25% from processes immunoreactive for glutamate. The relative distribution of the different classes of input were analysed from serial section reconstruction of terminal afferent branches. Inputs from GABA and glutamate-immunoreactive processes appeared to be scattered at random over the terminal arborisation of the afferents both with respect to each other and to the architecture of the terminals. They were, however, always found close to the output synapses. The possible roles of presynaptic inhibition in the auditory afferents is discussed in the context of the auditory responses of the animals.

  14. 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.

  15. 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.

  16. Complex interactions of NO/cGMP/PKG systems on Ca2+ signaling in afferent arteriolar vascular smooth muscle.

    PubMed

    Fellner, Susan K; Arendshorst, William J

    2010-01-01

    Little is known about the effects of nitric oxide (NO) and the cyclic GMP (cGMP)/protein kinase G (PKG) system on Ca(2+) signaling in vascular smooth muscle cells (VSMC) of resistance vessels in general and afferent arterioles in particular. We tested the hypotheses that cGMP-, Ca(2+)-dependent big potassium channels (BK(Ca(2+))) buffer the Ca(2+) response to depolarization by high extracellular KCl and that NO inhibits adenosine diphosphoribose (ADPR) cyclase, thereby reducing the Ca(2+)-induced Ca(2+) release. We isolated rat afferent arterioles, utilizing the magnetized microsphere method, and measured cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2, a preparation in which endothelial cells do not participate in [Ca(2+)](i) responses. KCl (50 mM)-induced depolarization causes an immediate increase in [Ca(2+)](i) of 151 nM. The blockers N(omega)-nitro-L-arginine methyl ester (of nitric oxide synthase), 1,2,4-oxodiazolo-[4,3-a]quinoxalin-1-one (ODQ, of guanylyl cyclase), KT-5823 (of PKG activation), and iberiotoxin (IBX, of BK(Ca(2+)) activity) do not alter the [Ca(2+)](i) response to KCl, suggesting no discernible endogenous NO production under basal conditions. The NO donor sodium nitroprusside (SNP) reduces the [Ca(2+)](i) response to 77 nM; IBX restores the response to control values. These data show that activation of BK(Ca(2+)) in the presence of NO/cGMP provides a brake on KCl-induced [Ca(2+)](i) responses. Experiments with the inhibitor of cyclic ADPR 8-bromo-cyclic ADPR (8-Br-cADPR) and SNP + downstream inhibitors of PKG and BK(Ca(2+)) suggest that NO inhibits ADPR cyclase in intact arterioles. When we pretreat afferent arterioles with 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP; 10 muM), the response to KCl is 143 nM. However, in the presence of both IBX and 8-Br-cGMP, we observe a surprising doubling of the [Ca(2+)](i) response to KCl. In summary, we present evidence for effects of the NO/cGMP/PKG system to reduce [Ca(2+)](i), via

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

    PubMed Central

    Kewin, Kevin; Jordan, Paivi M.; Cameron, Peter; Klapczynski, Marcin; McIntosh, J. Michael; Crooks, Peter A.; Dwoskin, Linda P.; Lysakowski, Anna

    2015-01-01

    Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton afferents. We recorded from CD and bouton afferents innervating the turtle posterior crista during electrical stimulation of vestibular efferents while applying several subtype-selective nAChR agonists and antagonists. The α9α10 nAChR antagonists, α-bungarotoxin and α-conotoxin RgIA, blocked efferent-mediated inhibition in bouton afferents while leaving efferent-mediated excitation in CD units largely intact. Conversely, 5-iodo-A-85380, sazetidine-A, varenicline, α-conotoxin MII, and bPiDDB (N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide) blocked efferent-mediated excitation in CD afferents without affecting efferent-mediated inhibition in bouton afferents. This pharmacological profile suggested that calyceal nAChRs contain α6 and β2, but not α9, nAChR subunits. Selective blockade of efferent-mediated excitation in CD afferents distinguished dimorphic from calyx afferents by revealing type II hair cell input. Dimorphic afferents differed in having higher mean discharge rates and a mean efferent-mediated excitation that was smaller in amplitude yet longer in duration. Molecular biological data demonstrated the expression of α9 in turtle hair cells and α4 and β2 in associated vestibular ganglia. PMID:25716861

  2. Physiological and anatomical characteristics of primary vestibular afferent neurons in the bullfrog.

    PubMed

    Honrubia, V; Sitko, S; Kimm, J; Betts, W; Schwartz, I

    1981-01-01

    Intracellular recordings were made in the VIIIth nerve of the bullfrog (Rana catesbiana) to measure the membrane characteristics and obtain records of spontaneous and evoked spike activity of primary semicircular canal afferents. Physiological stimulation of the canals was achieved by rotating the preparation on a servomotor driven turntable with the animals' head centered in the rotational axis. The responses of each neuron to sinusoidal rotations at frequencies of 0.05Hz, 0.5Hz and for impulsive accelerations of 400 deg/sec2 were obtained. Membrane characteristics measured included the cell resting and action potential amplitude, and spike-activation threshold for applied currents. Physiologically characterized neurons were injected with horseradish peroxidase by applying pneumatic pressure and/or iontophoretic currents to the micropipettes containing 5% HRP in 1 M KCI. Following survival times of 12--48 h, the VIIIth nerve and attached vestibular end organ was removed for histochemical processing using a diaminobenzidine procedure to visualize the HRP reaction product. Light microscopy was used to discern the anatomical features of the neurons and to trace their peripheral dendritic trajectories from the ganglion to their termination(s) in the crista. Our studies have revealed that the bullfrog's primary vestibular afferents are characterized by a broad range of soma and axon diameters which correspond to an equally broad range of spontaneous and evoked activity characteristics. The largest neurons had more irregular spontaneous firing rates and consistently exhibited the greatest gain and smallest phase shifts with respect to head acceleration. These neurons consistently terminated at or near the central region of the crista. On the other hand, the smallest neurons were characterized by having the most regular spontaneous discharge patterns, the lowest gains, and greatest phase shifts with respect to head acceleration. Our findings are thus consistent with the

  3. Increased hypoxic ventilatory sensitivity during exercise in man: are neural afferents necessary?

    PubMed Central

    Pandit, J J; Bergstrom, E; Frankel, H L; Robbins, P A

    1994-01-01

    1. The acute ventilatory response to 3 min periods of hypoxia (AHR) was examined in nine patients with clinically complete spinal cord transection (T4-T7) during (a) rest and (b) electrically induced leg exercise (EEL). 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee against gravity. End-tidal PCO2 was held constant 1-2 mmHg above resting values throughout both protocols. 3. On exercise, the average increase in metabolic CO2 production (VCO2 +/- S.E.M.) was 41 +/- 5 ml min-1. Venous lactate levels did not rise with exercise. 4. Baseline euoxic ventilation did not increase significantly with EEL, but there was a consistent and highly significant increase in the ventilatory response to hypoxia during EEL (mean delta AHR +/- S.E.M. of 1.6 +/- 0.21 min-1). 5. We conclude that an increase in hypoxic sensitivity during exercise can occur in the absence of volitional control of exercise and in the absence of afferent neural input from the limbs. PMID:8071884

  4. 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.

  5. Specific amino acids inhibit food intake via the area postrema or vagal afferents.

    PubMed

    Jordi, Josua; Herzog, Brigitte; Camargo, Simone M R; Boyle, Christina N; Lutz, Thomas A; Verrey, François

    2013-11-15

    To maintain nutrient homeostasis the central nervous system integrates signals that promote or inhibit eating. The supply of vital amino acids is tuned by adjusting food intake according to its dietary protein content. We hypothesized that this effect is based on the sensing of individual amino acids as a signal to control food intake. Here, we show that food intake was most potently reduced by oral L-arginine (Arg), L-lysine (Lys) and L-glutamic acid (Glu) compared to all other 17 proteogenic amino acids in rats. These three amino acids induced neuronal activity in the area postrema and the nucleus of the solitary tract. Surgical lesion of the area postrema abolished the anorectic response to Arg and Glu, whereas vagal afferent lesion prevented the response to Lys. These three amino acids also provoked gastric distension by differentially altering gastric secretion and/or emptying. Importantly, these peripheral mechanical vagal stimuli were dissociated from the amino acids' effect on food intake. Thus, Arg, Lys and Glu had a selective impact on food processing and intake suggesting them as direct sensory input to assess dietary protein content and quality in vivo. Overall, this study reveals novel amino acid-specific mechanisms for the control of food intake and of gastrointestinal function.

  6. The human spinal cord interprets velocity-dependent afferent input during stepping.

    PubMed

    Beres-Jones, Janell A; Harkema, Susan J

    2004-10-01

    We studied the motor response to modifying the rate of application of sensory input to the human spinal cord during stepping. We measured the electromyographic (EMG), kinematic and kinetic patterns of the legs during manually assisted or unassisted stepping using body weight support on a treadmill (BWST) in eight individuals with spinal cord injury (SCI). At various treadmill speeds (0.27-1.52 m/s), we measured the EMG activity of the soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA), medial hamstrings (MH), vastus lateralis (VL), rectus femoris (RF) and iliopsoas (ILIO); the hip, knee and ankle joint angles; the amount of body weight support (BWS); and lower limb loading. The EMG amplitude and burst duration of the SOL, MG, TA, MH, VL, RF and ILIO were related to the step cycle duration during stepping using BWST. EMG mean amplitudes increased at faster treadmill speeds, and EMG burst durations shortened with decreased step cycle durations. Muscle stretch of an individual muscle could not account for the EMG amplitude modulation in response to stepping speed. The effects on the EMG amplitude and burst duration were similar in subjects with partial and no detectable supraspinal input. We propose that the human spinal cord can interpret complex step-related, velocity-dependent afferent information to contribute to the neural control of stepping.

  7. 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

  8. Linear Path Integration Deficits in Patients with Abnormal Vestibular Afference

    PubMed Central

    Arthur, Joeanna C.; Kortte, Kathleen B.; Shelhamer, Mark; Schubert, Michael C.

    2014-01-01

    Effective navigation requires the ability to keep track of one’s location and maintain orientation during linear and angular displacements. Path integration is the process of updating the representation of body position by integrating internally-generated self-motion signals over time (e.g., walking in the dark). One major source of input to path integration is vestibular afference. We tested patients with reduced vestibular function (unilateral vestibular hypofunction, UVH), patients with aberrant vestibular function (benign paroxysmal positional vertigo, BPPV), and healthy participants (controls) on two linear path integration tasks: experimenter-guided walking and target-directed walking. The experimenter-guided walking task revealed a systematic underestimation of self-motion signals in UVH patients compared to the other groups. However, we did not find any difference in the distance walked between the UVH group and the control group for the target-directed walking task. Results from neuropsychological testing and clinical balance measures suggest that the errors in experimenter-guided walking were not attributable to cognitive and/or balance impairments. We conclude that impairment in linear path integration in UVH patients stem from deficits in self-motion perception. Importantly, our results also suggest that patients with a UVH deficit do not lose their ability to walk accurately without vision to a memorized target location. PMID:22726251

  9. 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

  10. 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.

  11. Cytosolic calcium regulation in rat afferent vagal neurons during anoxia.

    PubMed

    Henrich, Michael; Buckler, Keith J

    2013-12-01

    Sensory neurons are able to detect tissue ischaemia and both transmit information to the brainstem as well as release local vasoactive mediators. Their ability to sense tissue ischaemia is assumed to be primarily mediated through proton sensing ion channels, lack of oxygen however may also affect sensory neuron function. In this study we investigated the effects of anoxia on isolated capsaicin sensitive neurons from rat nodose ganglion. Acute anoxia triggered a reversible increase in [Ca2+]i that was mainly due to Ca2+-efflux from FCCP sensitive stores and from caffeine and CPA sensitive ER stores. Prolonged anoxia resulted in complete depletion of ER Ca2+-stores. Mitochondria were partially depolarised by acute anoxia but mitochondrial Ca2+-uptake/buffering during voltage-gated Ca2+-influx was unaffected. The process of Ca2+-release from mitochondria and cytosolic Ca2+-clearance following Ca2+ influx was however significantly slowed. Anoxia was also found to inhibit SERCA activity and, to a lesser extent, PMCA activity. Hence, anoxia has multiple influences on [Ca2+]i homeostasis in vagal afferent neurons, including depression of ATP-driven Ca2+-pumps, modulation of the kinetics of mitochondrial Ca2+ buffering/release and Ca2+-release from, and depletion of, internal Ca2+-stores. These effects are likely to influence sensory neuronal function during ischaemia. PMID:24189167

  12. Differential inhibitory control of semicircular canal nerve afferent-evoked inputs in second-order vestibular neurons by glycinergic and GABAergic circuits.

    PubMed

    Biesdorf, Stefan; Malinvaud, David; Reichenberger, Ingrid; Pfanzelt, Sandra; Straka, Hans

    2008-04-01

    Labyrinthine nerve-evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in second-order vestibular neurons (2 degrees VN) sum with disynaptic inhibitory postsynaptic potentials (IPSPs) that originate from the thickest afferent fibers of the same nerve branch and are mediated by neurons in the ipsilateral vestibular nucleus. Pharmacological properties of the inhibition and the interaction with the afferent excitation were studied by recording monosynaptic responses of phasic and tonic 2 degrees VN in an isolated frog brain after electrical stimulation of individual semicircular canal nerves. Specific transmitter antagonists revealed glycine and GABA(A) receptor-mediated IPSPs with a disynaptic onset only in phasic but not in tonic 2 degrees VN. Compared with GABAergic IPSPs, glycinergic responses in phasic 2 degrees VN have larger amplitudes and a longer duration and reduce early and late components of the afferent nerve-evoked subthreshold activation and spike discharge. The difference in profile of the disynaptic glycinergic and GABAergic inhibition is compatible with the larger number of glycinergic as opposed to GABAergic terminal-like structures on 2 degrees VN. The increase in monosynaptic excitation after a block of the disynaptic inhibition in phasic 2 degrees VN is in part mediated by a N-methyl-d-aspartate receptor-activated component. Although inhibitory inputs were superimposed on monosynaptic EPSPs in tonic 2 degrees VN as well, the much longer latency of these IPSPs excludes a control by short-latency inhibitory feed-forward side-loops as observed in phasic 2 degrees VN. The differential synaptic organization of the inhibitory control of labyrinthine afferent signals in phasic and tonic 2 degrees VN is consistent with the different intrinsic signal processing modes of the two neuronal types and suggests a co-adaptation of intrinsic membrane properties and emerging network properties. PMID:18256163

  13. 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

  14. Silent damage of noise on cochlear afferent innervation in guinea pigs and the impact on temporal processing.

    PubMed

    Liu, Lijie; Wang, Hui; Shi, Lijuan; Almuklass, Awad; He, Tingting; Aiken, Steve; Bance, Manohar; Yin, Shankai; Wang, Jian

    2012-01-01

    Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs "silently" in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period. PMID:23185359

  15. Octreotide inhibits capsaicin-induced activation of C and Aδ afferent fibres in rat hairy skin in vivo.

    PubMed

    Wang, Jun; Cao, Dong-Yuan; Guo, Yuan; Ma, Shao-Jie; Luo, Rong; Pickar, Joel G; Zhao, Yan

    2011-08-01

    1. The present study investigated whether the somatostatin receptor (SSTR) agonist, octreotide, could inhibit the activation of dorsal skin afferent fibres induced by local injection of capsaicin in the rat. 2. Single unit activity from Aδ mechano-heat sensitive (AMH; n = 41) and C mechano-heat sensitive (CMH; n = 30) afferents was recorded after their isolation in thin filaments from the dorsal cutaneous nerve branches. The effect of subcutaneous octreotide injection on the change in discharge rate and mechanical threshold induced by capsaicin was determined. 3. Capsaicin (0.05%) injection into the edge of the receptive field of both AMH and CMH units increased their discharge rate and decreased their mechanical threshold. Pre-injection of octreotide inhibited these responses, and co-application of SSTR antagonist, cyclosomatostatin, reversed the inhibitory effect of octreotide. 4. The present study provides electrophysiological evidence that the signal evoked by the somatostatin receptor inhibits the activation and mechanical sensitization evoked by capsaicin in the terminals in small-diameter sensory neurons.

  16. [Muscle afferent block in the treatment of oromandibular dystonia. Difference in effect between masticatory and lingual muscles].

    PubMed

    Yoshida, K

    2003-06-01

    Oromandibular dystonia is a neuromuscular disorder characterized by tonic or clonic involuntary spasms of the masticatory and lingual muscles. We treated 50 patients with this movement disorder by injection of lidocaine and alcohol into the masticatory or tongue muscles to block muscle afferents from muscle spindle. The patients were divided according to clinical features into four groups: jaw-closing, jaw-opening, jaw-deviation, and tongue dystonias. Objective evaluation of the symptoms before and after therapy was based on a clinical scaling protocol in terms of four parameters (mastication, speech, pain, and discomfort scales). Symptoms improved in all patients without major side effects. The overall objective improvement (60.2+/-29.5%) was significantly (P<0.005, ANOVA) lower in tongue dystonia (14.1%) than in jaw-closing dystonia (67.6%) and jaw-opening dystonia (68.3%). Although the response of the muscle afferent block to tongue dystonia was hardly satisfactory, this treatment is suggested to be effective for oromandibular dystonia.

  17. 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.

  18. NEUROTROPHIN SELECTIVITY IN ORGANIZING TOPOGRAPHIC REGENERATION OF NOCICEPTIVE AFFERENTS

    PubMed Central

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M.

    2015-01-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP+) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4+ non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFR-α3, which only promoted mistargeted regeneration. PMID:26054884

  19. [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.

  20. Effects of stimulation of vesical afferents on colonic motility in cats.

    PubMed

    Bouvier, M; Grimaud, J C; Abysique, A

    1990-05-01

    The effects of distension and isovolumetric contraction of urinary bladder on colonic motility were studied in anesthetized cats. Distension and contraction of the urinary bladder induced an inhibition of spontaneous colonic electromyographic activity and a decrease in the amplitudes of the excitatory junction potentials evoked in the colon by stimulation of the distal end of the parasympathetic nerve fibers. This inhibition was blocked by guanethidine and phentolamine. Reversely, vesical emptying resulted in an increase in colonic motility, abolished by atropine, and an increase in the amplitude of the excitatory junction potentials. Both excitatory and inhibitory reflexes disappeared after hexamethonium. The inhibitory effects of bladder distension were abolished by bilateral section of the lumbar ventral or dorsal spinal roots and after bilateral section of the lumbar colonic or hypogastric nerves. These results indicate (a) that the vesical afferents responsible for the inhibitory and excitatory reflexes run in the hypogastric and pelvic nerves respectively and (b) that the inhibitory and excitatory effects are caused by the activation of sympathetic and parasympathetic efferent nerve fibers, respectively. The supraspinal nervous structures were not implicated in these reflexes because they persisted in spinal cats.

  1. Ascending auditory interneurons in the cricket Teleogryllus commodus (Walker): comparative physiology and direct connections with afferents.

    PubMed

    Hennig, R M

    1988-05-01

    Ascending auditory interneurons of the cricket, Teleogryllus commodus (Walker), were investigated using simultaneous intracellular and extracellular recording in order to identify units which had previously been characterized only by extracellular recording. The morphology and physiology of the large adapting unit (LAU: Fig. 1) and of the small tonic unit (STU: Fig. 2) of Teleogryllus correspond well to those of the ascending neuron 2 (AN2) and the ascending neuron 1 (AN1) of Gryllus (Figs. 1, 2), respectively. A summary of the ascending auditory interneurons described by various authors in 5 species of crickets is presented in order to establish common identities. Physiological evidence for direct connections between auditory afferents and the ascending auditory interneurons AN1 (STU) and AN2 (LAU) is presented. Simultaneous intracellular recordings from receptors and interneurons in response to sound as well as the activity of auditory interneurons upon electrical stimulation of the tympanal nerve reveal short and constant latencies of receptor-evoked synaptic activity in AN1 (STU) and AN2 (LAU).

  2. 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

  3. Central projections of the wing afferents in the hawkmoth, Agrius convolvuli.

    PubMed

    Ando, Noriyasu; Wang, Hao; Shirai, Koji; Kiguchi, Kenji; Kanzaki, Ryohei

    2011-11-01

    Flight behaviors in various insect species are closely correlated with their mechanical and neuronal properties. Compared to locusts and flies which have been intensively studied, moths have "intermediate" properties in terms of the neurogenic muscle activations, power generation by indirect muscles, and two-winged-insect-like flapping behavior. Despite these unique characteristics, little is known about the neuronal mechanisms of flight control in moths. We investigated projections of the wing mechanosensory afferents in the central nervous system (CNS) of the hawkmoth, Agrius convolvuli, because the mechanosensory proprioceptive feedback has an essential role for flight control and would be presumably optimized for insect species. We conducted anterograde staining of nine afferent nerves from the fore- and hindwings. All of these afferents projected into the prothoracic, mesothoracic and metathoracic ganglia (TG1, 2 and 3) and had ascending fibers to the head ganglia. Prominent projection areas in the TG1-3 and suboesophageal ganglion (SOG) were common between the forewing, hindwing and contralateral forewing afferents, suggesting that information from different wings are converged at multiple levels presumably for coordinating wing flapping. On the other hand, differences of projections between the fore- and hindwing afferents were observed especially in projection areas of the tegulae in the TG1 and contralateral projections of the anterior forewing nerve in the TGs and SOG, which would reflect functional differences between corresponding mechanoreceptors on each wing. Afferents comprising groups of the campaniform sensilla at the wing bases had prominent ascending pathways to the SOG, resembling the head-neck motor system for gaze control in flies. Double staining of the wing afferents and flight or neck motoneurons also indicated potential connectivity between them. Our results suggest multiple roles of the wing proprioceptive feedback for flight and provide

  4. 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

  5. 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.

  6. 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

  7. Structure-function relationships in rat medullary and cervical dorsal horns. I. Trigeminal primary afferents.

    PubMed

    Jacquin, M F; Renehan, W E; Mooney, R D; Rhoades, R W

    1986-06-01

    Intracellular recording and horseradish peroxidase (HRP) labeling were used to examine structure-function relationships in the medullary dorsal horn (MDH) and rostral cervical dorsal horn. In Nembutal-anesthetized rats, 78 trigeminal (V) primary afferent fibers were physiologically characterized and injected with HRP. Axons were sufficiently well stained to reconstruct all of their collaterals in the MDH. Many also extended into the cervical dorsal horn. Except for four axons, which responded best to noxious stimuli, all responded at short (mean = 0.50 ms) latencies to V ganglion shocks and to innocuous stimulation. Forty-five of our recovered fibers were associated with facial vibrissae and responded in either a rapidly adapting, slowly adapting type I, slowly adapting type IIa, or slowly adapting type IIb fashion. The adequate stimuli consisted of either slow deflection, high-velocity deflection, or a noxious pinch of the vibrissa follicle. The collaterals of all of the above-described mystacial vibrissa primary afferents proceeded directly to their region of arborization in a plane perpendicular to the lateral border of the medulla to collectively form a largely continuous, circumscribed terminal column. This longitudinally oriented column of terminal and en passant boutons angled from lamina V rostrally to lamina III caudally. In the magnocellular laminae of the MDH, all mystacial vibrissa primary afferents gave rise to similarly shaped arbors, regardless of their functional classification. While morphological variability was observed both within and between individual axons, variance between functional classes was no greater than that within a class. Moreover, number of collaterals, number of boutons, or bouton size did not distinguish functional classes. Nonmystacial vibrissa afferent arbors, with more caudal peripheral fields, had their primary arbor focus in C1 and C2 dorsal horn. These arbors had relatively little rostrocaudal overlap with mystacial

  8. 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

  9. Cutaneous afferent input does not modulate motor intracortical inhibition in ageing men.

    PubMed

    Smith, Ashleigh E; Ridding, Michael C; Higgins, Ryan D; Wittert, Gary A; Pitcher, Julia B

    2011-11-01

    Afferent input has been shown to be a powerful modulator of cortical inhibition. Such modulation is likely to be important for the control of ongoing movement, but may also play a role in facilitating neuroplastic reorganisation. Human motor control and neuroplasticity both decline with ageing, whereas the efficacy of short-interval intracortical inhibition (SICI) appears not to. We examined if ageing alters the efficacy of afferent modulation of SICI. Previously, electrical cutaneous stimulation of a finger has been shown to reduce SICI in the motor cortices of young adults. Paired-pulse transcranial magnetic stimulation was used to assess SICI in the cortical representation of the first dorsal interosseous muscle. SICI was assessed separately under two conditions: with and without prior afferent input from electrical cutaneous stimulation of the index finger. Fifteen 'young' (20.1 ± 2.1 years) and 15 'old' male humans (65.5 ± 3.9 years) were studied. SICI did not differ when young and old males were compared. However, when preceded by electrical cutaneous finger stimulation, SICI was reduced in young men but not old men. Reflex testing indicated preservation of the afferent volley to the cortex. These findings suggest that a contributing factor in the decline of motor function, and possibly neuroplasticity, with ageing is loss of SICI modulation, probably due to altered cortical sensorimotor integration of afferent input.

  10. Inhibition of repulsive guidance molecule, RGMa, increases afferent synapse formation with auditory hair cells.

    PubMed

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

    2014-04-01

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

  11. Cyclic GMP-dependent and cyclic GMP-independent actions of nitric oxide on the renal afferent arteriole

    PubMed Central

    Trottier, Greg; Triggle, Chris R; O'Neill, Sean K; Loutzenhiser, Rodger

    1998-01-01

    The effects of exogenous NO and endothelial-derived NO (EDNO) on the afferent arteriole were investigated in the in vitro perfused hydronephrotic rat kidney. Vessels were pre-constricted with angiotensin II (0.1–0.3 nM) or KCl (30 mM). NO was infused directly into the renal artery at concentrations ranging from 30–9000 nM. ODQ (10, 30 μM) was administered to examine the effects of guanylyl cyclase inhibition. Kidneys were treated with ibuprofen (10 μM) to avoid actions of prostaglandins.During angiotensin II-induced vasoconstriction, NO elicited vasodilation at concentrations of 30–900 nM (EC50=200 nM) and ODQ caused a 10 fold shift in NO-sensitivity (EC50 1600 nM). During KCl-induced vasoconstriction, NO elicited a maximal dilation of 82±9% at 9000 nM (EC50 2000 nM) and ODQ had no effect. Thus in the presence of ODQ, the NO concentration-response curves for KCl- and angiotensin II-induced vasoconstriction were identical (P>0.2).To assess the possible role of cyclic GMP-independent mechanisms in the actions of EDNO, we compared the effects of L-NAME, ODQ and ODQ+L-NAME on acetylcholine-induced vasodilation. Angiotensin II reduced afferent arteriolar diameters from 16.7±0.5 to 8.1±0.8 microns and acetylcholine fully reversed this effect (16.9±0.5 microns). ODQ restored the angiotensin II response in the presence of acetylcholine (7.1±0.6 microns) and the subsequent addition of L-NAME had no further effect (6.8±0.7 microns). Similarly, L-NAME alone, fully reversed the actions of acetylcholine.Our findings indicate that exogenous NO is capable of eliciting renal afferent arteriolar vasodilation through both cyclic GMP-dependent and cyclic GMP-independent mechanisms. The cyclic GMP-independent action of NO did not require K+ channel activation, as it could be elicited in the presence of 30 mM KCl. Finally, although cyclic GMP-independent effects of exogenous NO could be demonstrated in our model, EDNO appears to act exclusively

  12. 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

  13. Vagal afferent projections to lobule VIIa of the rabbit cerebellar vermis related to cardiovascular control.

    PubMed

    Kondo, M; Sears, T A; Sadakane, K; Nisimaru, N

    1998-02-01

    In decerebrate rabbits we recorded simultaneously field potentials in lobule VIIa of the vermal cerebellar cortex and the vagal compound action potentials (vCAPs) proximally in the vagus nerve following electrical stimulation distally in the same nerve at different intensities. Four principal components of the vCAP were distinguished based on their peak conduction velocities. Their velocities were component I, 67-100 m/s; II, 28-50 m/s; III, 6-28 m/s, IV, 0.4-1.3 m/s. A collision test based on stimulating the recurrent laryngeal nerve identified component I and sub-component IIa of the vCAP as being due to the motor fibres of the descending limb of the nerve. The field potentials evoked in lobule VIIa by electrical stimulation of the cervical vagus nerve were climbing fibre responses as judged by the characteristics of their lamina profile and their response to high frequency stimulation. These field potentials in lobule VIIa correlated most closely with the component III of the vCAP; particularly with a sub-component IIIa of the vagus. Based on the investigations by Evans and Murray (1954) (Histological and functional studies on the fibre composition of the vagus nerve of the rabbit. J. Anat. (Lond.) 88, 320-337) in the rabbit, and by Paintal (1963) (Vagal afferent fibres. Ergeb. Physiol. 52, 74-156) and Mei (1970) (Cardiovascular and respiratory vagal mechanoreceptors in the cat. Exp. Brain Res. 11, 480-501) in the cat, component III is most likely to be due to receptors from the heart and a part of the pulmonary stretch receptors.

  14. Facilitation of the swallowing reflex with bilateral afferent input from the superior laryngeal nerve.

    PubMed

    Takahashi, Kojiro; Shingai, Tomio; Saito, Isao; Yamamura, Kensuke; Yamada, Yoshiaki; Kitagawa, Junichi

    2014-03-01

    To determine the cooperative effect of laryngeal afferent signals on the swallowing reflex, we examined whether afferent signals originating from the left and right superior laryngeal nerve (SLN) modulates elicitation of the swallowing reflex in urethane-anesthetized rats. Mylohyoid electromyographic activity was recorded to quantify the swallowing reflex. The onset latency of the swallowing reflex and the time intervals between successive swallows were used to quantify and compare the effects of unilateral and bilateral electrical stimulations of the SLN. The mean latency of the first swallow and the mean time interval between swallows evoked with low frequency stimulation were both significantly different between unilateral and bilateral stimulations of the SLN. These findings suggest that facilitatory effect of afferent signals originating from the SLN bilaterally increase the motoneuronal activity in the medullary swallowing center and enhance the swallowing reflex.

  15. Distribution of primary afferent fibres in the cochlear nuclei. A silver and horseradish peroxidase (HRP) study.

    PubMed Central

    Merchan, M A; Collia, F P; Merchan, J A; Saldana, E

    1985-01-01

    Horseradish peroxidase, when injected intracochlearly, is transported transganglionically to the brain stem cochlear nuclei, thus providing an excellent method for tracing the central projection of the spiral ganglion neurons. Silver impregnation using the Cajal-de Castro method, which stains axons even when inside the bone, was used as a reference technique. The combination of both procedures led to the following conclusions. Primary cochlear afferents are found only in the ventral zone of the dorsal cochlear nucleus. In this area they cover the deep and fusiform cell layers. The molecular layer shows no HRP label. The higher concentration of primary cochlear afferents in the ventral cochlear nucleus appears in its central zone; wide areas in this nucleus are not labelled at all. A thin bundle of primary cochlear afferents runs parallel to, and beneath, the granular region. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:4077711

  16. Primary afferent fibers establish dye-coupled connections in the frog central nervous system.

    PubMed

    Bácskai, Timea; Matesz, Clara

    Neurobiotin and Lucifer yellow, indicators of gap junctional coupling, were applied to primary afferent fibers of the frog. Following application of tracers to cervical or lumbar dorsal root fibers, a large number of labeled granule cells were detected in the corpus cerebelli, the brainstem, and the spinal cord. The vestibular nerve was found to be in dye-coupled connection with the granule cells of the auricular lobe of the cerebellum. After application of the tracers to the trigeminal nerve, elicited dye-coupled neurons located mainly in the termination area of the descending limb of the mesencephalic trigeminal nucleus. In control experiments with biotinylated dextrane amine, only primary afferent fibers were labeled. Our results suggest that gap junctional coupling exists between primary afferent fibers and their postsynaptic targets in the frog.

  17. Management of afferent loop obstruction from recurrent metastatic pancreatic cancer using a venting gastrojejunostomy

    PubMed Central

    Bakes, Debbie; Cain, Christian; King, Michael; Dong, Xiang Da (Eric)

    2013-01-01

    Pancreatic cancer is an aggressive malignancy potentially curable with surgical intervention. Following pancreaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immediate and delayed problems due to surgical complications and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduodenectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percutaneous biliary decompression. During surgical exploration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical approach for management of this complicated and difficult problem. PMID:24363832

  18. Rapid development of Purkinje cell excitability, functional cerebellar circuit, and afferent sensory input to cerebellum in zebrafish.

    PubMed

    Hsieh, Jui-Yi; Ulrich, Brittany; Issa, Fadi A; Wan, Jijun; Papazian, Diane M

    2014-01-01

    The zebrafish has significant advantages for studying the morphological development of the brain. However, little is known about the functional development of the zebrafish brain. We used patch clamp electrophysiology in live animals to investigate the emergence of excitability in cerebellar Purkinje cells, functional maturation of the cerebellar circuit, and establishment of sensory input to the cerebellum. Purkinje cells are born at 3 days post-fertilization (dpf). By 4 dpf, Purkinje cells spontaneously fired action potentials in an irregular pattern. By 5 dpf, the frequency and regularity of tonic firing had increased significantly and most cells fired complex spikes in response to climbing fiber activation. Our data suggest that, as in mammals, Purkinje cells are initially innervated by multiple climbing fibers that are winnowed to a single input. To probe the development of functional sensory input to the cerebellum, we investigated the response of Purkinje cells to a visual stimulus consisting of a rapid change in light intensity. At 4 dpf, sudden darkness increased the rate of tonic firing, suggesting that afferent pathways carrying visual information are already active by this stage. By 5 dpf, visual stimuli also activated climbing fibers, increasing the frequency of complex spiking. Our results indicate that the electrical properties of zebrafish and mammalian Purkinje cells are highly conserved and suggest that the same ion channels, Nav1.6 and Kv3.3, underlie spontaneous pacemaking activity. Interestingly, functional development of the cerebellum is temporally correlated with the emergence of complex, visually-guided behaviors such as prey capture. Because of the rapid formation of an electrically-active cerebellum, optical transparency, and ease of genetic manipulation, the zebrafish has great potential for functionally mapping cerebellar afferent and efferent pathways and for investigating cerebellar control of motor behavior.

  19. 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

  20. Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1.

    PubMed

    Ditting, Tilmann; Freisinger, Wolfgang; Rodionova, Kristina; Schatz, Johannes; Lale, Nena; Heinlein, Sonja; Linz, Peter; Ott, Christian; Schmieder, Roland E; Scrogin, Karie E; Veelken, Roland

    2016-03-01

    Recently, we showed that renal afferent neurons exhibit a unique firing pattern, i.e., predominantly sustained firing, upon stimulation. Pathological conditions such as renal inflammation likely alter excitability of renal afferent neurons. Here, we tested whether the proinflammatory chemokine CXCL1 alters the firing pattern of renal afferent neurons. Rat dorsal root ganglion neurons (Th11-L2), retrogradely labeled with dicarbocyanine dye, were incubated with CXCL1 (20 h) or vehicle before patch-clamp recording. The firing pattern of neurons was characterized as tonic, i.e., sustained action potential (AP) firing, or phasic, i.e., <5 APs following current injection. Of the labeled renal afferents treated with vehicle, 58.9% exhibited a tonic firing pattern vs. 7.8%, in unlabeled, nonrenal neurons (P < 0.05). However, after exposure to CXCL1, significantly more phasic neurons were found among labeled renal neurons; hence the occurrence of tonic neurons with sustained firing upon electrical stimulation decreased (35.6 vs. 58.9%, P < 0.05). The firing frequency among tonic neurons was not statistically different between control and CXCL1-treated neurons. However, the lower firing frequency of phasic neurons was even further decreased with CXCL1 exposure [control: 1 AP/600 ms (1-2) vs. CXCL1: 1 AP/600 ms (1-1); P < 0.05; median (25th-75th percentile)]. Hence, CXCL1 shifted the firing pattern of renal afferents from a predominantly tonic to a more phasic firing pattern, suggesting that CXCL1 reduced the sensitivity of renal afferent units upon stimulation.

  1. 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

  2. A quantitative study of the central projection patterns of unmyelinated ventral root afferents in the cat.

    PubMed Central

    Häbler, H J; Jänig, W; Koltzenburg, M; McMahon, S B

    1990-01-01

    1. The ventral roots of the spinal cord contain a large number of unmyelinated primary afferent neurones. There is some controversy, however, about the function of these fibres and the route of their central projection. Here we have used electrophysiological techniques to quantify the central projection patterns of these neurones in the segment S2 of adult chloralose-anaesthesized cats. 2. A total of 1185 single unmyelinated units were recorded in small filaments isolated from intact and de-efferented ventral roots or intact dorsal roots of the segment S2 in nineteen cats. The projection patterns of these neurones were tested using supramaximal electrical stimulation of the pelvic and pudendal nerve (the main tributaries of the spinal nerve of this segment) and of the segmental companion root (dorsal or ventral as appropriate). 3. The principal finding of this study is that 85% of unmyelinated afferent axons in the ventral root are direct and exclusive projections. They constitute a separate class of afferents which is only capable of transmitting information from the periphery via the ventral roots. However, the proportion of these fibres that enter the central nervous system is unknown and it seems likely that some of them peter out as they approach the spinal cord and end blindly. The functional role of such afferents remains obscure. 4. For the remaining 15% of unmyelinated ventral root afferents, a projection into the segmental dorsal root was found. The majority of those fibres (about two-thirds) are primary afferent neurones innervating the pia mater. Some of these units had a small spot-like receptive field and responded to mechanical stimuli such as pressure and stretch of the root. They did not have axon projections in a peripheral nerve. 5. A few (5%) unmyelinated ventral root fibres are collateral branches of normal primary afferents projecting through the dorsal root. These trifurcating neurones are a small population which make up only some 0.5% of

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

    PubMed Central

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

    2011-01-01

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

  4. 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

  5. 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

  6. Afferents to the GABAergic tail of the ventral tegmental area in the rat.

    PubMed

    Kaufling, Jennifer; Veinante, Pierre; Pawlowski, Sophie A; Freund-Mercier, Marie-Jose; Barrot, Michel

    2009-04-20

    We previously showed that chronic psychostimulant exposure induces the transcription factor DeltaFosB in gamma-aminobutyric acid (GABA)ergic neurons of the caudal tier of the ventral tegmental area (VTA). This subregion was defined as the tail of the VTA (tVTA). In the present study, we showed that tVTA can also be visualized by analyzing FosB/DeltaFosB response following acute cocaine injection. This induction occurs in GABAergic neurons, as identified by glutamic acid decarboxylase (GAD) expression. To characterize tVTA further, we mapped its inputs by using the retrograde tracers Fluoro-Gold or cholera toxin B subunit. Retrogradely labeled neurons were observed in the medial prefrontal cortex, the lateral septum, the ventral pallidum, the bed nucleus of the stria terminalis, the substantia innominata, the medial and lateral preoptic areas, the lateral and dorsal hypothalamic areas, the lateral habenula, the intermediate layers of the superior colliculus, the dorsal raphe, the periaqueductal gray, and the mesencephalic and pontine reticular formation. Projections from the prefrontal cortex, the hypothalamus, and the lateral habenula to the tVTA were also shown by using the anterograde tracer biotinylated dextran amine (BDA). We showed that the central nucleus of the amygdala innervates the anterior extent of the VTA but not the tVTA. Moreover, the tVTA mainly receives non-aminergic inputs from the dorsal raphe and the locus coeruleus. Although the tVTA has a low density of dopaminergic neurons, its afferents are mostly similar to those targeting the rest of the VTA. This suggests that the tVTA can be considered as a VTA subregion despite its caudal location.

  7. Selective impact of Tau loss on nociceptive primary afferents and pain sensation.

    PubMed

    Sotiropoulos, Ioannis; Lopes, André T; Pinto, Vitor; Lopes, Sofia; Carlos, Sara; Duarte-Silva, Sara; Neves-Carvalho, Andreia; Pinto-Ribeiro, Filipa; Pinheiro, Sara; Fernandes, Rui; Almeida, Armando; Sousa, Nuno; Leite-Almeida, Hugo

    2014-11-01

    Tau protein hyperphosphorylation and consequent malfunction are hallmarks of Alzheimer's disease pathology; importantly, pain perception is diminished in these patients. In physiological conditions, Tau contributes to cytoskeletal dynamics and in this way, influences a number of cellular mechanisms including axonal trafficking, myelination and synaptic plasticity, processes that are also implicated in pain perception. However, there is no in vivo evidence clarifying the role of Tau in nociception. Thus, we tested Tau-null (Tau-/-) and Tau+/+ mice for acute thermal pain (Hargreaves' test), acute and tonic inflammatory pain (formalin test) and mechanical allodynia (Von Frey test). We report that Tau-/- animals presented a decreased response to acute noxious stimuli when compared to Tau+/+ while their pain-related behavior is augmented under tonic painful stimuli. This increased reactivity to tonic pain was accompanied by enhanced formalin-evoked c-fos staining of second order nociceptive neurons at Tau-null dorsal horn. In addition, we analyzed the primary afferents conveying nociceptive signals, estimating sciatic nerve fiber density, myelination and nerve conduction. Ultrastructural analysis revealed a decreased C-fiber density in the sciatic nerve of Tau-null mice and a hypomyelination of myelinated fibers (Aδ-fibers) - also confirmed by western blot analysis - followed by altered conduction properties of Tau-null sciatic nerves. To our knowledge, this is the first in vivo study that demonstrates that Tau depletion negatively affects the main systems conveying nociceptive information to the CNS, adding to our knowledge about Tau function(s) that might also be relevant for understanding peripheral neurological deficits in different Tauopathies.

  8. [Cervical echomyography in cervical dystonia and its application to the monitoring for muscle afferent block (MAB)].

    PubMed

    Mezaki, T; Matsumoto, S; Sakamoto, T; Mizutani, K; Kaji, R

    2000-07-01

    Muscle afferent block (MAB) is an intramuscular injection of 0.5% lidocaine and pure ethanol with a volume ratio of 10:1, introduced as an alternative to botulinum toxin injection for focal dystonia and spasticity. As in the case of botulinum toxin injection, the precise localization of target muscles is crucial to obtain the maximal effect from MAB. For this purpose, we performed ultrasonography of cervical muscles (echomyography) in 20 patients with cervical dystonia (11 men, 9 women; mean age 46.1), with ultrasonograph SSD-5500 (Aloca Co. Ltd., Japan) and a 7.5 MHz linear probe. In untreated subjects, the boundaries of muscles could be easily identified, while they tended to become ambiguous after repeated MAB sessions. At rest, there were involuntary worm-like movements of a specific muscle group observed in all patients. Contrary to our expectation, in all but one patient abnormal contraction was limited only in a part of synergists responsible for the abnormal posture. In normal subjects there was no abnormal contraction at rest, and all the synergists were simultaneously activated by the voluntary neck deviation. Normal subjects could not mimick the pattern of muscle activity in dystonic patients. The echo-guided MAB was performed in 16 patients. We could easily observe the diffusion of lidocaine and ethanol into the targeted muscle, and injected portions of the muscle stopped their activities just after MAB. The effect persisted for 3-4 days in at least 5 out of 10 patients who had follow-up examination. On the other hand, the movement stopped only temporarily after the injection of saline or lidocaine only. In 3 out of 16 patients, some of the uninjected synergists were activated as if to substitute for the treated muscle just after the injection. We conclude that cervical echomyography is useful to investigate the pattern of muscle activity in cervical dystonia and to accurately localize the contracting muscles during MAB.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Effects of reduced plantar cutaneous afferent feedback on locomotor adjustments in dynamic stability during perturbed walking.

    PubMed

    Höhne, Angela; Stark, Christian; Brüggemann, Gert-Peter; Arampatzis, Adamantios

    2011-08-11

    This study examined the effects of reduced plantar cutaneous afferent feedback on predictive and feedback adaptive locomotor adjustments in dynamic stability during perturbed walking. Twenty-two matched participants divided between an experimental-group and a control-group performed a gait protocol, which included surface alterations to one covered exchangeable gangway-element (hard/soft). In the experimental-group, cutaneous sensation in both foot soles was reduced to the level of sensory peripheral neuropathy by means of intradermal injections of an anaesthetic solution, without affecting foot proprioception or muscles. The gait protocol consisted of baseline trials on a uniformly hard surface and an adaptation phase consisting of nineteen trials incorporating a soft gangway-element, interspersed with three trials using the hard surface-element (2nd, 8th and 19th). Dynamic stability was assessed by quantifying the margin of stability (MS), which was calculated as the difference between the base of support (BS) and the extrapolated centre of mass (CM). The horizontal velocity of the CM and its vertical projection in the anterior-posterior direction and the eigenfrequency of an inverted pendulum determine the extrapolated-CM. Both groups increased the BS at the recovery step in response to the first unexpected perturbation. These feedback corrections were used more extensively in the experimental-group, which led to a higher MS compared to the control-group, i.e. a more stable body-position. In the adaptation phase the MS returned to baseline similarly in both groups. In the trial on the hard surface directly after the first perturbation, both groups increased the MS at touchdown of the disturbed leg compared to baseline trials, indicating rapid predictive adjustments irrespective of plantar cutaneous input. Our findings demonstrate that the locomotor adaptational potential does not decrease due to the loss of plantar sensation.

  14. 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

  15. Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure.

    PubMed

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei

    2008-09-01

    Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

  16. 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.

  17. 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

  18. Human C-Tactile Afferents Are Tuned to the Temperature of a Skin-Stroking Caress

    PubMed Central

    Backlund Wasling, Helena; Liljencrantz, Jaquette; Olausson, Håkan; Johnson, Richard D.; Wessberg, Johan

    2014-01-01

    Human C-tactile (CT) afferents respond vigorously to gentle skin stroking and have gained attention for their importance in social touch. Pharmacogenetic activation of the mouse CT equivalent has positively reinforcing, anxiolytic effects, suggesting a role in grooming and affiliative behavior. We recorded from single CT axons in human participants, using the technique of microneurography, and stimulated a unit's receptive field using a novel, computer-controlled moving probe, which stroked the skin of the forearm over five velocities (0.3, 1, 3, 10, and 30 cm s−1) at three temperatures (cool, 18°C; neutral, 32°C; warm, 42°C). We show that CTs are unique among mechanoreceptive afferents: they discharged preferentially to slowly moving stimuli at a neutral (typical skin) temperature, rather than at the cooler or warmer stimulus temperatures. In contrast, myelinated hair mechanoreceptive afferents proportionally increased their firing frequency with stroking velocity and showed no temperature modulation. Furthermore, the CT firing frequency correlated with hedonic ratings to the same mechano-thermal stimulus only at the neutral stimulus temperature, where the stimuli were felt as pleasant at higher firing rates. We conclude that CT afferents are tuned to respond to tactile stimuli with the specific characteristics of a gentle caress delivered at typical skin temperature. This provides a peripheral mechanism for signaling pleasant skin-to-skin contact in humans, which promotes interpersonal touch and affiliative behavior. PMID:24553929

  19. Differential effects of plantar cutaneous afferent excitation on soleus stretch and H-reflex.

    PubMed

    Sayenko, Dimitry G; Vette, Albert H; Obata, Hiroki; Alekhina, Maria I; Akai, Masami; Nakazawa, Kimitaka

    2009-06-01

    Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuron excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents in modulating the excitability of stretch and H-reflex with respect to the location of their excitation remains unclear. In the present study, it was hypothesized that electrical stimulation delivered to the sole of the foot might be followed by modulation of spinal excitability that depends on: (1) the stimulation location and (2) the reflex studied. In these experiments, conditioned and unconditioned stretch and H-reflexes were evoked in 16 healthy subjects in a seated position. Both reflexes were conditioned by non-noxious electrical plantar cutaneous afferent stimulation at two different sites, the heel and metatarsal regions, at four different conditioning-test (CT) intervals. The conditioning stimulation delivered to the heel caused a significant facilitation of the soleus stretch reflex for all CT intervals, whereas the soleus H-reflex had significant facilitation only at CT interval of 50 ms and significant inhibition at longer CT intervals. Stimulation delivered to the metatarsal region, however, resulted mainly in reduced stretch and H-reflex sizes. This study extends the reported findings on the contribution of plantar cutaneous afferents within spinal interneuron reflex circuits as a function of their location and the reflex studied. PMID:19260052

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

    PubMed

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

    2013-09-15

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

  1. 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.

  2. 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

  3. 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. PMID:26660356

  4. Human C-tactile afferents are tuned to the temperature of a skin-stroking caress.

    PubMed

    Ackerley, Rochelle; Backlund Wasling, Helena; Liljencrantz, Jaquette; Olausson, Håkan; Johnson, Richard D; Wessberg, Johan

    2014-02-19

    Human C-tactile (CT) afferents respond vigorously to gentle skin stroking and have gained attention for their importance in social touch. Pharmacogenetic activation of the mouse CT equivalent has positively reinforcing, anxiolytic effects, suggesting a role in grooming and affiliative behavior. We recorded from single CT axons in human participants, using the technique of microneurography, and stimulated a unit's receptive field using a novel, computer-controlled moving probe, which stroked the skin of the forearm over five velocities (0.3, 1, 3, 10, and 30 cm s(-1)) at three temperatures (cool, 18 °C; neutral, 32 °C; warm, 42 °C). We show that CTs are unique among mechanoreceptive afferents: they discharged preferentially to slowly moving stimuli at a neutral (typical skin) temperature, rather than at the cooler or warmer stimulus temperatures. In contrast, myelinated hair mechanoreceptive afferents proportionally increased their firing frequency with stroking velocity and showed no temperature modulation. Furthermore, the CT firing frequency correlated with hedonic ratings to the same mechano-thermal stimulus only at the neutral stimulus temperature, where the stimuli were felt as pleasant at higher firing rates. We conclude that CT afferents are tuned to respond to tactile stimuli with the specific characteristics of a gentle caress delivered at typical skin temperature. This provides a peripheral mechanism for signaling pleasant skin-to-skin contact in humans, which promotes interpersonal touch and affiliative behavior. PMID:24553929

  5. 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

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

    PubMed Central

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

    2013-01-01

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

  7. Timing of medullary late-inspiratory neuron discharges: vagal afferent effects indicate possible off-switch function.

    PubMed

    Cohen, M I; Huang, W X; Barnhardt, R; See, W R

    1993-05-01

    1. In decerebrate paralyzed cats, we observed the responses of ventral and dorsal medullary inspiratory (I) neurons to two types of vagal afferent input that shorten neural I: lung inflation and vagal electrical stimulation. 2. A study population of 15 I neurons whose firing patterns suggested involvement in the inspiratory OFF-switch (IOS) was selected on the basis of two criteria: late onset of firing and excitation by vagal inputs. 3. Firing in relation to the end of I showed two types of response to vagal inputs. The pre-expiratory onset time (time from initial spike to end of I) was either unchanged (type 1 response in 5/15 neurons) or significantly changed (type 2 response in 10/15 neurons). 4. It is suggested that type 1 neurons, whose firing patterns remain closely locked to the end of I despite considerable changes of I duration, are involved in promoting the IOS, whereas type 2 neurons are either not involved (e.g., late-onset premotor neurons) or are involved at an earlier temporal processing stage. PMID:8389840

  8. Cerebral, subcortical, and cerebellar activation evoked by selective stimulation of muscle and cutaneous afferents: an fMRI study

    PubMed Central

    Wardman, Daniel L.; Gandevia, Simon C.; Colebatch, James G.

    2014-01-01

    Abstract We compared the brain areas that showed significant flow changes induced by selective stimulation of muscle and cutaneous afferents using fMRI BOLD imaging. Afferents arising from the right hand were studied in eight volunteers with electrical stimulation of the digital nerve of the index finger and over the motor point of the FDI muscle. Both methods evoked areas of significant activation cortically, subcortically, and in the cerebellum. Selective muscle afferent stimulation caused significant activation in motor‐related areas. It also caused significantly greater activation within the contralateral precentral gyrus, insula, and within the ipsilateral cerebellum as well as greater areas of reduced blood flow when compared to the cutaneous stimuli. We demonstrated separate precentral and postcentral foci of excitation with muscle afferent stimulation. We conclude, contrary to the findings with evoked potentials, that muscle afferents evoke more widespread cortical, subcortical, and cerebellar activation than do cutaneous afferents. This emphasizes the importance, for studies of movement, of matching the kinematic aspects in order to avoid the results being confounded by alterations in muscle afferent activation. The findings are consistent with clinical observations of the movement consequences of sensory loss and may also be the basis for the contribution of disturbed sensorimotor processing to disorders of movement. PMID:24771687

  9. Peripheral patterns of terminal innervation of vestibular primary afferent neurons projecting to the vestibulocerebellum in the gerbil.

    PubMed

    Purcell, I M; Perachio, A A

    2001-04-23

    Retrograde transganglionic labeling techniques with biotinylated dextran amine (BDA) were used to examine the terminal field structure and topographical patterns of innervation within the vestibular sensory end organs of vestibular primary afferent neurons projecting to the cerebellar uvula/nodulus and flocculus lobules in the gerbil. Robust, dark labeling in the cristae ampullares suggested that the vast majority of the terminals of afferent neurons were of the dimorphic type. The majority (94% to the uvula/nodulus and 100% to the flocculus) innervates the peripheral zones of each of the three semicircular canal cristae. Comparison of the type and distribution of terminals across the canalicular sensory neuroepithelium with morphophysiological studies in chinchilla suggests that the labeled population consists predominantly of peripheral terminal fields of lower-to-intermediate gain, more regularly firing, tonic afferents. For otolith organ-related afferents, the uvula/nodulus receives strong inputs from primary otolith afferent neurons identified as dimorphic in type that predominately innervate the peristriolar zones of the utricular and saccular maculae. No direct otolith organ-related inputs to the flocculus were observed. In contrast to the canal afferents, the types and locations of labeled otolith afferent terminals suggest that they largely consist of irregularly firing, high-gain, phasic neurons. PMID:11283948

  10. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

    PubMed

    Fenwick, Axel J; Wu, Shaw-Wen; Peters, James H

    2014-01-01

    Cranial visceral afferents contained within the solitary tract (ST) contact second-order neurons in the nucleus of the solitary tract (NTS) and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33 to 37°C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

  11. Cardiovascular afferents cause the release of 5-HT in the nucleus tractus solitarii; this release is regulated by the low- (PMAT) not the high-affinity transporter (SERT)

    PubMed Central

    Hosford, Patrick S; Millar, Julian; Ramage, Andrew G

    2015-01-01

    Key points The nucleus tractus solitarii (NTS) integrates visceral afferent information essential for cardiovascular haemostasis. Using fast-cyclic voltammetry in anaesthetized rats, 5-HT (serotonin) release was detected in NTS in response to activation of these afferents. Removal of 5-HT from the extracellular space is usually regulated by the low-capacity, high-affinity 5-HT transporter (5-HTT/SERT). The present data demonstrate that 5-HT removal in the NTS is regulated by the plasma membrane monoamine transporter (PMAT), a high-capacity, low-affinity transporter. The present data also demonstrate that the 5-HT released by afferent activation comes from at least two different sources. It is suggested that one of these sources is the afferents themselves. These results demonstrate a physiological role for the low-affinity uptake transporter in the regulation of 5-HT concentration in NTS. Abstract The nucleus tractus solitarii (NTS) integrates inputs from cardiovascular afferents and thus is crucial for cardiovascular homeostasis. These afferents primarily release glutamate, although 5-HT has also been shown to play a role in their actions. Using fast-cyclic voltammetry, an increase in 5-HT concentrations (range 12–50 nm) could be detected in the NTS in anaesthetized rats in response to electrical stimulation of the vagus and activation of cardiopulmonary, chemo- and baroreceptor reflexes. This 5-HT signal was not potentiated by the serotonin transporter (SERT) or the noradrenaline transporter (NET) inhibitors citalopram and desipramine (1 mg kg−1). However, decynium-22 (600 μg kg−1), an organic cation 3 transporter (OCT3)/plasma membrane monoamine transporter (PMAT) inhibitor, increased the 5-HT signal by 111 ± 21% from 29 ± 10 nm. The effectiveness of these inhibitors was tested against the removal time of 5-HT and noradrenaline applied by microinjection to the NTS. Citalopram and decynium-22 attenuated the removal of 5-HT but not

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

    PubMed

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

    2010-05-01

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Afferent-specific properties of interneuron synapses underlie selective long-term regulation of feedback inhibitory circuits in CA1 hippocampus.

    PubMed

    Croce, Ariane; Pelletier, Joe Guillaume; Tartas, Maylis; Lacaille, Jean-Claude

    2010-06-15

    Hebbian long-term potentiation (LTP) develops at specific synapses onto hippocampal CA1 oriens/alveus interneurons (OA-INs), suggesting selective regulation of distinct input pathways. Afferent-specific properties at interneuron synapses have been characterized extensively in CA3 stratum lucidum cells, but given interneuron diversity these rules of transmission and plasticity may not hold in other interneuron types. Here, we used paired recordings and demonstrate that CA2/3 pyramidal cell (PC) feedforward and CA1 PC feedback synapses onto OA-INs show distinct AMPA receptor rectification and Ca(2+) permeability, short-term plasticity and mGluR2/3-mediated inhibition. Only feedback synapses undergo Hebbian LTP. OA-IN firing during repeated synaptic stimulation displays onset-transient or late-persistent responses consistent with activation of feedforward and feedback inputs, respectively. Input-output functions are preserved after theta-burst stimulation, but late-persistent responses selectively show mGluR1-dependent long-term increases. Thus, cell type- and afferent-specific rules of transmission and plasticity underlie distinct OA-IN input-output functions, providing selective long-term regulation in feedback inhibitory networks.

  18. 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

  19. 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

  20. Opioids inhibit visceral afferent activation of catecholamine neurons in the solitary tract nucleus

    PubMed Central

    Cui, Ran Ji; Roberts, Brandon L.; Zhao, Huan; Andresen, Michael C.; Appleyard, Suzanne M.

    2014-01-01

    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 EPSCs (ST-EPSCs) in NTS TH-EGFP neurons by 80%, an effect reversed by wash or the mu opioid receptor specific antagonist, 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 glutamate release and elucidate one potential mechanism by which opioids

  1. 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

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

    PubMed

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

    2014-08-01

    Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. PMID:25100607

  3. Afferent projection patterns in the auditory brainstem in normal and congenitally deaf white cats.

    PubMed

    Heid, S; Jähn-Siebert, T K; Klinke, R; Hartmann, R; Langner, G

    1997-08-01

    Cochlear implantation in congenitally deaf children is developing to a successful medical tool. Little is known, however, on morphology and pathophysiology of the central auditory system in these auditory deprived children. One form of congenital hearing loss, that seen in the deaf white cat, was investigated to see if there are differences in the afferent pathways from the cochlear nuclei to the inferior colliculus. The retrogradely transported fluorescent tracer diamidino yellow (DY) was injected into different parts of the central nucleus of the inferior colliculus (ICC) of normal cats and deaf white cats. It was found that the main afferent projection patterns in deaf white cats were unchanged in spite of congenital auditory deprivation; minor differences were seen. PMID:9282901

  4. Electrohydraulic Lithotripsy of an Impacted Enterolith Causing Acute Afferent Loop Syndrome

    PubMed Central

    Cho, Young Sin; Hwang, Soon Oh; Lee, Sunhyo; Jung, Yunho; Chung, Il-Kwun; Park, Sang-Heum; Kim, Sun-Joo

    2014-01-01

    Afferent loop syndrome caused by an impacted enterolith is very rare, and endoscopic removal of the enterolith may be difficult if a stricture is present or the normal anatomy has been altered. Electrohydraulic lithotripsy is commonly used for endoscopic fragmentation of biliary and pancreatic duct stones. A 64-year-old man who had undergone subtotal gastrectomy and gastrojejunostomy presented with acute, severe abdominal pain for a duration of 2 hours. Initially, he was diagnosed with acute pancreatitis because of an elevated amylase level and pain, but was finally diagnosed with acute afferent loop syndrome when an impacted enterolith was identified by computed tomography. We successfully removed the enterolith using direct electrohydraulic lithotripsy conducted using a transparent cap-fitted endoscope without complications. We found that this procedure was therapeutically beneficial. PMID:25133128

  5. Netrin-1 Contributes to Myelinated Afferent Fiber Sprouting and Neuropathic Pain.

    PubMed

    Wu, Cai-Hua; Yuan, Xiao-Cui; Gao, Fang; Li, Hong-Ping; Cao, Jie; Liu, Yan-Shen; Yu, Wei; Tian, Bo; Meng, Xian-Fang; Shi, Jing; Pan, Hui-Lin; Li, Man

    2016-10-01

    Netrin-1 is a neuronal guidance molecule implicated in the development of spinal cord neurons and cortical neurons. In the adult spinal cord, UNC5H (repulsive receptor of netrin-1), but not deleted in colorectal cancer (DCC) (attractive receptor of netrin-1), constitutes a major mode of netrin-1 signal transduction, which may be involved in axon repulsion and inhibits neurite outgrowth. Abnormal sprouting of myelinated afferent fibers in the spinal dorsal horn can cause mechanical allodynia associated with postherpetic neuralgia (PHN, Shingles) and other neuropathic pains. However, whether netrin-1 participates in sprouting of myelinated afferent fibers and mechanical allodynia remains unknown. In an ultropotent TRPV1 agonist resiniferatoxin (RTX)-induced PHN-like model, RTX treatment for 6 weeks increased netrin-1 expression in dorsal horn neurons, including NK-1-positive projection neurons. In human neuroblastoma SH-SY5Y cells, we found that TRPV1 antagonist capsazepine antagonized RTX-induced upregulation of netrin-1. After RTX treatment, UNC5H2 expression was gradually decreased, whereas DCC expression was significantly increased. Silencing netrin-1 in the spinal dorsal horn significantly attenuated RTX-induced mechanical allodynia and sprouting of myelinated fibers into the spinal lamina II. Our results suggest that RTX treatment upregulates netrin-1 expression through activation of TRPV1 receptors and change UNC5H2-rich spinal dorsal horn into a growth-permissive environment by increasing DCC expression, thus enhancing the sprouting of myelinated afferent nerves. Netrin-1 may be targeted for reducing primary afferent sprouting and mechanical allodynia in PHN and other neuropathic pain conditions. PMID:26482371

  6. The proportions of sympathetic postganglionic and unmyelinated afferent axons in normal and regenerated cat sural nerves.

    PubMed

    Lisney, S J

    1988-03-01

    Electrophysiological experiments have been carried out to see if the proportions of sympathetic postganglionic and unmyelinated afferent axons in a cutaneous nerve were changed after injury and regeneration. It seemed possible that an alteration in the relative numbers of the two groups of axons could contribute to the aetiology of reflex sympathetic dystrophy, but the experiments provided no evidence for such a change. There were, however, signs of a decrease in axon numbers in the regenerated nerves. PMID:3379252

  7. 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

  8. Pseudogallbladder appearance in partial afferent loop obstruction in a patient with cholecystectomy

    SciTech Connect

    Morse, J.M.; Lakshman, S.; Thomas, E.

    1986-08-01

    We have described a patient who was admitted to the hospital for evaluation of RUQ abdominal pain 40 years after a Billroth II gastrectomy, as well as a cholecystectomy of which the patient was unaware. Gray-scale abdominal ultrasonography and Tc 99m-IDA hepatobiliary imaging were interpreted as revealing an enlarged gallbladder and cholelithiasis. An obstructed afferent loop of the Billroth II anastomosis had mimicked a gallbladder on ultrasonography and hepatobiliary imaging.

  9. Resting Discharge Patterns of Macular Primary Afferents in Otoconia-Deficient Mice

    PubMed Central

    Jones, S. M.; Hoffman, L. F.

    2008-01-01

    Vestibular primary afferents in the normal mammal are spontaneously active. The consensus hypothesis states that such discharge patterns are independent of stimulation and depend instead on excitation by vestibular hair cells due to background release of synaptic neurotransmitter. In the case of otoconial sensory receptors, it is difficult to test the independence of resting discharge from natural tonic stimulation by gravity. We examined this question by studying discharge patterns of single vestibular primary afferent neurons in the absence of gravity stimulation using two mutant strains of mice that lack otoconia (OTO−; head tilt, het-Nox3, and tilted, tlt-Otop1). Our findings demonstrated that macular primary afferent neurons exhibit robust resting discharge activity in OTO− mice. Spike interval coefficient of variation (CV = SD/mean spike interval) values reflected both regular and irregular discharge patterns in OTO− mice, and the range of values for rate-normalized CV was similar to mice and other mammals with intact otoconia although there were proportionately fewer irregular fibers. Mean discharge rates were slightly higher in otoconia-deficient strains even after accounting for proportionately fewer irregular fibers [OTO− = 75.4 ± 31.1(113) vs OTO+ = 68.1 ± 28.5(143) in sp/s]. These results confirm the hypothesis that resting activity in macular primary afferents occurs in the absence of ambient stimulation. The robust discharge rates are interesting in that they may reflect the presence of a functionally ‘up-regulated’ tonic excitatory process in the absence of natural sensory stimulation. PMID:18661184

  10. Netrin-1 Contributes to Myelinated Afferent Fiber Sprouting and Neuropathic Pain.

    PubMed

    Wu, Cai-Hua; Yuan, Xiao-Cui; Gao, Fang; Li, Hong-Ping; Cao, Jie; Liu, Yan-Shen; Yu, Wei; Tian, Bo; Meng, Xian-Fang; Shi, Jing; Pan, Hui-Lin; Li, Man

    2016-10-01

    Netrin-1 is a neuronal guidance molecule implicated in the development of spinal cord neurons and cortical neurons. In the adult spinal cord, UNC5H (repulsive receptor of netrin-1), but not deleted in colorectal cancer (DCC) (attractive receptor of netrin-1), constitutes a major mode of netrin-1 signal transduction, which may be involved in axon repulsion and inhibits neurite outgrowth. Abnormal sprouting of myelinated afferent fibers in the spinal dorsal horn can cause mechanical allodynia associated with postherpetic neuralgia (PHN, Shingles) and other neuropathic pains. However, whether netrin-1 participates in sprouting of myelinated afferent fibers and mechanical allodynia remains unknown. In an ultropotent TRPV1 agonist resiniferatoxin (RTX)-induced PHN-like model, RTX treatment for 6 weeks increased netrin-1 expression in dorsal horn neurons, including NK-1-positive projection neurons. In human neuroblastoma SH-SY5Y cells, we found that TRPV1 antagonist capsazepine antagonized RTX-induced upregulation of netrin-1. After RTX treatment, UNC5H2 expression was gradually decreased, whereas DCC expression was significantly increased. Silencing netrin-1 in the spinal dorsal horn significantly attenuated RTX-induced mechanical allodynia and sprouting of myelinated fibers into the spinal lamina II. Our results suggest that RTX treatment upregulates netrin-1 expression through activation of TRPV1 receptors and change UNC5H2-rich spinal dorsal horn into a growth-permissive environment by increasing DCC expression, thus enhancing the sprouting of myelinated afferent nerves. Netrin-1 may be targeted for reducing primary afferent sprouting and mechanical allodynia in PHN and other neuropathic pain conditions.

  11. 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.

  12. 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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    1996-01-01

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

  15. Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall.

    PubMed

    Hobson, Anthony R; Chizh, Boris; Hicks, Kirsty; Aziz, Qasim; Worthen, Sian; Lawrence, Philip; Dewit, Odile; Boyle, Yvonne; Dukes, George

    2010-01-01

    Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first

  16. Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents.

    PubMed

    Kras, Jeffrey V; Weisshaar, Christine L; Pall, Parul S; Winkelstein, Beth A

    2015-09-14

    Non-physiological stretch of the cervical facet joint's capsular ligament induces persistent behavioral hypersensitivity and spinal neuronal hyperexcitability via an intra-articular NGF-dependent mechanism. Although that ligament is innervated by nociceptors, it is unknown if a subpopulation is exclusively responsible for the behavioral and spinal neuronal responses to intra-articular NGF and/or facet joint injury. This study ablated joint afferents using the neurotoxin saporin targeted to neurons involved in either peptidergic ([Sar(9),Met (O2)(11)]-substance P-saporin (SSP-Sap)) or non-peptidergic (isolectin B4-saporin (IB4-Sap)) signaling to investigate the contributions of those neuronal populations to facet-mediated pain. SSP-Sap, but not IB4-Sap, injected into the bilateral C6/C7 facet joints 14 days prior to an intra- articular NGF injection prevents NGF-induced mechanical and thermal hypersensitivity in the forepaws. Similarly, only SSP- Sap prevents the increase in mechanical forepaw stimulation- induced firing of spinal neurons after intra-articular NGF. In addition, intra-articular SSP-Sap prevents both behavioral hypersensitivity and upregulation of NGF in the dorsal root ganglion after a facet joint distraction that normally induces pain. These findings collectively suggest that disruption of peptidergic signaling within the joint may be a potential treatment for facet pain, as well as other painful joint conditions associated with elevated NGF, such as osteoarthritis.

  17. Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. Laparoscopic Revision of an Omega Loop Gastric Bypass to Treat Afferent Loop Syndrome.

    PubMed

    Kassir, Radwan; Blanc, Pierre; Lointier, Patrice; Breton, Christophe; Debs, Tarek; Tiffet, Olivier

    2015-10-01

    The omega loop gastric bypass (OLGB) has become a very commonly performed bariatric procedure because of the advantages it carries over the Roux en Y gastric bypass (RYGBP). However, mini gastric bypass is a misnomer, as this procedure is more malabsorptive than the RYGBP. Recently, it is called single or one anastomosis gastric bypass. The omega loop procedure is associated with a risk of afferent loop syndrome, a known complication of the Billroth II (Finsterer) operation. This rare complication of the OLGB can be debilitating, serious, and deadly. Afferent loop syndrome should be suspected in case of malabsorption syndrome with chronic diarrhea, steatorrhea, iron-deficiency anemia, edema, emaciation, and osteomalacia and also in case of simple biological anomalies such as macrocytosis or megaloblastic anemia. The diagnosis can be confirmed by measuring bacterial overgrowth, although this requires a jejunal aspirate performed during endoscopy with jejunal intubation. A microbial population of more than 106 organisms per milliliter of aspirate is pathological. Afferent loop syndrome is encountered less frequently now that the number of gastrectomies has dropped. Yet, with the omega loop bypass procedure becoming more common, surgeons must again be made aware of this potential complication. PMID:26210192

  20. Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

    PubMed

    Brown, P B; Harton, P; Millecchia, R; Lawson, J; Kunjara-Na-Ayudhya, T; Stephens, S; Miller, M A; Hicks, L; Culberson, J

    2000-05-01

    We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93-106). One component of that model is a hypothesis that convergence and divergence of connections between low-threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833-848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account. PMID:10754502

  1. The neural signal of angular head position in primary afferent vestibular nerve axons

    PubMed Central

    Loe, P. R.; Tomko, David L.; Werner, G.

    1973-01-01

    1. The relation between discharge frequency and angular head position was determined for a population of regularly discharging single first-order vestibular neurones in the eighth nerve of the barbiturate anaesthetized cat. 2. Each axon had a characteristic head position which was maximally excitatory to it, and a diametrically opposed head position which was minimally excitatory. 3. After correction for phase shifts introduced by the orientation of preferred excitability, discharge rate in statoreceptor afferents varied as a power function of the sine of angular head position with exponents ranging from 0·9 to 1·6. 4. Experimentally determined discharge rates were compared with the predictions of a computer simulation model incorporating the idea that shearing force acting on morphologically polarized receptors is the adequate stimulus for macular receptor cells. 5. This approach permitted the identification of a population of first-order vestibular afferents whose discharge frequency varied with head position as did the magnitude of shear force computed for individual receptors, each most excited in a particular head position. 6. The majority of the spatial orientations of maximal sensitivity defined a surface which is tilted by approximately 30° with reference to the Horsley—Clarke horizontal plane, implying that most statoreceptor afferents are maximally sensitive to position changes when the cat's head is at or near its normal position. ImagesPlate 1Plate 2Plate 3 PMID:4702433

  2. Retinal Afferent Ingrowth to Neocortical Transplants in the Adult Rat Superior Colliculus is due to the Regeneration of Damaged Axons

    PubMed Central

    Ross, D. T.; Das, G. D.

    1994-01-01

    Retinal afferent ingrowth to embryonic neural transplants in the adult rat superior colliculus may represent either sprouting of intact axons or the regeneration of transected axons. If ingrowth represents regeneration of damaged retinofugai axons, then lesions that axotomize more retinofugal axons at the transplantation site should induce greater retinal afferent ingrowth. Alternately, if ingrowth represents terminal or collateral sprouting of intact retinofugal axons at or near the transplant/host optic layer interface, then the magnitude of retinal afferent ingrowth should be directly related to the total area of this interface. To test between these two hypotheses surgical knife wounds were made either parallel (in the sagittal plane) or perpendicular (in the transverse plane) to the course of axons in the stratum opticum, embryonic neocortical tissue was transplanted at the coordinates of these tectal slits, and retinal afferent ingrowth visualized 1-90 days after surgery using anterogradely transported HRP. A zone of traumatic reaction (ztr) in the optic layers was seen in every case, characterized by hypertrophied axons and swollen terminal clubs at 1 day. Between 30 and 90 days the damaged retinofugal axons in the zone formed dense fascicles and neuroma-like tangles. Retinal afferent ingrowth occurred only across transplant interface regions with the ztr. The magnitude of ingrowth was directly related to the area of the ztr interface and not the total optic layer interface area. Retinal afferent ingrowth appears to reflect the intrinsic regenerative capacity of adult mammalian retinal ganglion cells and not sprouting of undamaged axons. PMID:7703292

  3. Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity

    PubMed Central

    Heppner, Thomas J.; Tykocki, Nathan R.; Erickson, Cuixia Shi; Vizzard, Margaret A.; Nelson, Mark T.

    2015-01-01

    Social stress has been implicated as a cause of urinary bladder hypertrophy and dysfunction in humans. Using a murine model of social stress, we and others have shown that social stress leads to bladder overactivity. Here, we show that social stress leads to bladder overactivity, increased bladder compliance, and increased afferent nerve activity. In the social stress paradigm, 6-wk-old male C57BL/6 mice were exposed for a total of 2 wk, via barrier cage, to a C57BL/6 retired breeder aggressor mouse. We performed conscious cystometry with and without intravesical infusion of the TRPV1 inhibitor capsazepine, and measured pressure-volume relationships and afferent nerve activity during bladder filling using an ex vivo bladder model. Stress leads to a decrease in intermicturition interval and void volume in vivo, which was restored by capsazepine. Ex vivo studies demonstrated that at low pressures, bladder compliance and afferent activity were elevated in stressed bladders compared with unstressed bladders. Capsazepine did not significantly change afferent activity in unstressed mice, but significantly decreased afferent activity at all pressures in stressed bladders. Immunohistochemistry revealed that TRPV1 colocalizes with CGRP to stain nerve fibers in unstressed bladders. Colocalization significantly increased along the same nerve fibers in the stressed bladders. Our results support the concept that social stress induces TRPV1-dependent afferent nerve activity, ultimately leading to the development of overactive bladder symptoms. PMID:26224686

  4. Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats

    PubMed Central

    2015-01-01

    Myofascial trigger points (MTrPs) are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human) of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P < 0.01), and immunohistochemistry with Neurofilament 200 indicated more myelinated afferents existed in MTrSs (P < 0.01). Spontaneous electrical activity (SEA) recordings at MTrSs showed that specific block of myelinated afferents in sciatic nerve with tetrodotoxin (TTX) led to significantly decreased SEA (P < 0.05). Behavioral assessment showed that mechanical pain thresholds (MPTs) of MTrSs were lower than those of non-MTrSs (P < 0.01). Block of myelinated afferents by intramuscular TTX injection increased MPTs of MTrSs significantly (P < 0.01), while MPTs of non-MTrSs first decreased (P < 0.05) and then increased (P > 0.05). 30 min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P < 0.01). Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs. PMID:26064165

  5. Augmented activity of the pelvic nerve afferent mediated by TRP channels in dextran sulfate sodium (DSS)-induced colitis of rats.

    PubMed

    Makimura, Yukitoshi; Ito, Koichi; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2012-08-01

    Enteritis has been recognized as a major symptom in domestic animals and human patients suffering from feed and food poisonings. The aim of the present study was to clarify the excitatory mechanism of the pelvic nerve afferent which may influence the occurrence of enteritis in response to nociceptive chemical stimuli of the colon in normal and abnormal rats with colitis induced by dextran sulfate sodium (DSS). The pelvic nerve afferent activity was markedly increased by colonic instillation of solution (0.5 ml) of acetic acid (5-25%) and capsaicin (100 μg/ml). The nerve activity was augmented by colonic instillation of capsaicin to a greater extent in rats with DSS-induced colitis than in normal control rats. This augmented activity by capsaicin was more prominent at one day (DSS-1) than at 8 day (DSS-8) after the administration of DSS. The increased nerve activity caused by capsaicin in DSS-1 and DSS-8 was significantly inhibited by pretreatment with ruthenium red, which is a nonselective inhibitor of TRP channels of unmyelinated C-fibers (nociceptors). In conclusion, it was elucidated that the nociceptive function of the pelvic nerve was largely elevated at one day after DSS-induced colitis and such increased function was mostly mediated by TRP channels.

  6. Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations.

    PubMed

    de Veer, Michael; Neeland, Melanie; Burke, Melissa; Pleasance, Jill; Nathanielsz, Jackie; Elhay, Martin; Meeusen, Els

    2013-02-01

    After vaccination, innate cell populations transport antigen from the tissue, via the afferent lymphatic vessels, into the local lymph node where they provide critical signals for the generation of an adaptive immune response. The present study uses a unique lymphatic cannulation model to examine, in real time, changes in afferent lymph after injection of a liposome-based delivery system, incorporating diptheria toxoid (DT) and the innate stimulator, poly(I:C). There was a dramatic but temporal recruitment of innate cell populations over time, with neutrophils and monocytes peaking at 6h and 28h post vaccination respectively. The number of dendritic cells (DC) did not increase over the 198h time period, while lymphocytes were slightly elevated at the latest times, indicating the start of an adaptive response. Monocytes and neutrophils were the predominant cell types transporting antigen at the early time points while DC were the most dominant antigen-carrying cells after 78h, predominantly the Sirp-α(high) DC subtype. Resuspending liposomes in oil instead of aqueous solutions has recently been shown to dramatically increase the level and persistence of an immune response and forms the basis of the novel adjuvant formulations, Vaccimax© and Depovax©. In the present study, formulation of the DT and poly(I:C) containing liposomes in an oil carrier dramatically reduced antigen transport to the draining lymph nodes. Examination of the injection site revealed the creation of an ectopic lymphoid tissue with prominent antigen foci and organized lymphoid cells, providing a possible mechanism for the persistence of an immune response in liposome-in-oil adjuvant formulation. Together, the present studies demonstrate the real-time innate in vivo response to vaccination of two novel liposome-based adjuvant systems and the dramatic effect of different carrier formulations.

  7. Factors influencing the therapeutic effect of muscle afferent block for oromandibular dystonia and dyskinesia: implications for their distinct pathophysiology.

    PubMed

    Yoshida, K; Kaji, R; Shibasaki, H; Iizuka, T

    2002-10-01

    Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary masticatory and/or lingual muscle contractions. Muscle afferent block (MAB) by injecting anaesthetic and alcohol intramuscularly is recently used for the treatment of OMD. To study the factors affecting the efficacy of MAB, 44 patients with OMD were treated by local injection of lidocaine and ethanol. They were divided into four groups (spastic, rhythmic, dyskinetic, and task-specific) according to the pattern of incisal movement and involuntary contraction. We used a clinical scaling protocol in terms of four parameters (mastication, speech, pain, and discomfort) to evaluate the change of symptoms objectively. The relationship of improvement in clinical scores with various parameters was assessed statistically. The overall objective improvement was 60.2 +/- 29.5%. The scores decreased significantly (P<0.0001, paired t-test) after MAB. The maximal incisal velocity significantly correlated inversely with the clinical improvement, and MAB was particularly effective for spastic contraction. Dyskinetic and rhythmic groups showed variable and significantly less improvements than the spastic group. MAB is highly effective for OMD, but not for the patients with dyskinetic symptoms. The jaw movement pattern is an important factor for predicting the outcome. The difference in the response to MAB in OMD and oral and/or orofacial dyskinesia suggests the distinct pathophysiology between the two.

  8. Quantitative assessment of the effects of pupillary dilation on aqueous flare in eyes with chronic anterior uveitis using laser flare photometry.

    PubMed

    Ikeji, Felicia; Pavesio, Carlos; Bunce, Catey; White, Edward

    2010-10-01

    The purpose of this study is to determine whether pupillary dilation has any effect on anterior chamber flare measurements using a Kowa laser flare meter (FM-500) in patients with chronic anterior uveitis (CAU). Twenty-five eyes of 25 consecutive patients with CAU were assessed for anterior chamber inflammation by an experienced operator using the Kowa laser flare meter. Ten measurements were taken in total, with the highest and the lowest measurements deducted. The mean value and standard deviation was then recorded. One drop of tropicamide 1% and phenylephrine 2.5% was then applied and after 30 min the measurements were repeated and the results recorded. Sixteen women (64%) and nine men (36%) were recruited. The majority of patients were white Caucasian (68%). Fifteen left and ten right eyes were studied and the median (interquartile range: IQR) visual acuity was 6/9 (6/6-6/18). Iris colour was classified as brown, blue, grey/hazel and hazel. Thirteen eyes (52%) had brown irises, eight (32%) had blue, two had grey and the remainder were grey/hazel and hazel. The mean (SD) age was 50.8 (12.59) years. The median (IQR) flare reading before dilation was 17.93 (8.33-29.93) and after dilation was 15.97 (10.17-29.4). The mean change was -0.74 which was not a statistically significantly different to 0 (P=0.25) and the 95% limits of agreements ranged from -6.91 to 5.43. This study showed little evidence of any systematic difference between dilated and undilated flare measurements. The measurement of flare was not affected by the dilation of the pupil and measurements could be taken before or after papillary dilation for the purpose of patient follow-up data and clinical studies. PMID:20502943

  9. Sutureless clear corneal DSAEK with a modified approach for preventing pupillary block and graft dislocation: case series with retrospective comparative analysis.

    PubMed

    Titiyal, Jeewan S; Tinwala, Sana I; Shekhar, Himanshu; Sinha, Rajesh

    2015-04-01

    The purpose of this study was to describe a modified technique of sutureless DSAEK with continuous pressurized internal air tamponade. This was a prospective interventional case series, single-center, institutional study. Twenty-seven patients with corneal decompensation without scarring were included. Aphakic patients and patients with cataractous lens requiring IOL implantation surgery were excluded. Following preparation of the donor tissue, a corneal tunnel was made nasally with two side ports. All incisions were kept long enough to be overlapped by the peripheral part of the donor tissue. Descemet membrane scoring was done using a reverse Sinskey hook, following which it was removed with the same instrument or by forceps. The donor lenticule was then inserted using Busin's glide. Continuous pressurized internal air tamponade was achieved by means of a 30-gauge needle, inserted through the posterior limbus, for 12-14 min. At the end of the surgery, air was partially replaced with BSS, leaving a moderate-sized mobile air bubble in the anterior chamber. At the 6 month's follow-up, CDVA improved from counting fingers at half meter-6/24 preoperatively to 6/9-6/18 postoperatively, and the mean endothelial cell count decreased: to 1,800 from 2,200 cell/mm(2) preoperatively (18.19 % endothelial cell loss). Donor lenticule thickness as documented on AS-OCT was 70-110 µ on Day 1 and 50-80 µ at 6 months postoperative. None of the cases had flat AC or peripheral anterior synechiae formation. None of the patients required a second intervention. There were no cases of primary graft failure, pupillary block glaucomax or donor lenticule dislocation postoperatively. Our modified technique is simple and effective with reduction in postoperative complications associated with DSAEK, thereby maximizing anatomic and functional outcomes associated. PMID:24728534

  10. Quantitative assessment of the effects of pupillary dilation on aqueous flare in eyes with chronic anterior uveitis using laser flare photometry.

    PubMed

    Ikeji, Felicia; Pavesio, Carlos; Bunce, Catey; White, Edward

    2010-10-01

    The purpose of this study is to determine whether pupillary dilation has any effect on anterior chamber flare measurements using a Kowa laser flare meter (FM-500) in patients with chronic anterior uveitis (CAU). Twenty-five eyes of 25 consecutive patients with CAU were assessed for anterior chamber inflammation by an experienced operator using the Kowa laser flare meter. Ten measurements were taken in total, with the highest and the lowest measurements deducted. The mean value and standard deviation was then recorded. One drop of tropicamide 1% and phenylephrine 2.5% was then applied and after 30 min the measurements were repeated and the results recorded. Sixteen women (64%) and nine men (36%) were recruited. The majority of patients were white Caucasian (68%). Fifteen left and ten right eyes were studied and the median (interquartile range: IQR) visual acuity was 6/9 (6/6-6/18). Iris colour was classified as brown, blue, grey/hazel and hazel. Thirteen eyes (52%) had brown irises, eight (32%) had blue, two had grey and the remainder were grey/hazel and hazel. The mean (SD) age was 50.8 (12.59) years. The median (IQR) flare reading before dilation was 17.93 (8.33-29.93) and after dilation was 15.97 (10.17-29.4). The mean change was -0.74 which was not a statistically significantly different to 0 (P=0.25) and the 95% limits of agreements ranged from -6.91 to 5.43. This study showed little evidence of any systematic difference between dilated and undilated flare measurements. The measurement of flare was not affected by the dilation of the pupil and measurements could be taken before or after papillary dilation for the purpose of patient follow-up data and clinical studies.

  11. Sex- and afferent-specific differences in histamine receptor expression in vagal afferents of rats: A potential mechanism for sexual dimorphism in prevalence and severity of asthma.

    PubMed

    Li, J N; Li, X L; He, J; Wang, J X; Zhao, M; Liang, X B; Zhao, S Y; Ma, M N; Liu, Y; Wang, Y B; Chen, H; Qiao, G F; Li, B Y

    2015-09-10

    The incidence of asthma is more common in boys than in girls during the childhood, and more common in premenopausal female than age-matched males. Our previous study demonstrated a gender difference in histamine-mediated neuroexcitability in nodose ganglia neurons (NGNs), highlighting a possibility of histamine-mediated gender difference in asthma via visceral afferent function. In the present study, we aimed to explore the gender difference in expression profiles of histamine receptors (HRs) in nodose ganglia (NG) and individual identified NGNs to provide deeper insights into the mechanisms involved in sexual dimorphism of asthma. Western-blot and SYBR green RT-PCR showed that H2R and H3R were highly expressed in NG of females compared with males and downregulated in ovariectomized females. H1R was equally expressed in NG of both sexes and not altered by ovariectomy. Furthermore, this highly expressive H2R and H3R were distributed in both myelinated and unmyelinated NGNs isolated from adult female rats by immunofluorescence and single-cell RT-PCR. H3R widely distributed in all tested neuron subtypes and its expression did not show significant difference among neuron subtypes. H2R was widely and highly expressed in low-threshold and sex-specific subpopulation of myelinated Ah-types compared with myelinated A- and unmyelinated C-type NGNs. Unexpectedly, weak expression of H1R was detected in both myelinated and unmyelinated NGNs by immunofluorescence, which was further confirmed by single-cell RT-PCR. Our results suggest that the sexual dimorphism in the expression of H2R and H3R in vagal afferents very likely contributes, at least partially, to the gender difference in prevalence and severity of asthma.

  12. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses

    PubMed Central

    Fenwick, Axel J.; Wu, Shaw-wen; Peters, James H.

    2014-01-01

    Cranial visceral afferents contained within the solitary tract (ST) contact second-order neurons in the nucleus of the solitary tract (NTS) and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33 to 37°C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals. PMID:24550768

  13. Stability of long term facilitation and expression of zif268 and Arc in the spinal cord dorsal horn is modulated by conditioning stimulation within the physiological frequency range of primary afferent fibers.

    PubMed

    Haugan, F; Wibrand, K; Fiskå, A; Bramham, C R; Tjølsen, A

    2008-07-17

    Long term facilitation (LTF) of C-fiber-evoked firing of wide dynamic range neurons in the spinal dorsal horn in response to conditioning stimulation (CS) of afferent fibers is a widely studied cellular model of spinal nociceptive sensitization. Although 100 Hz CS of primary afferent fibers is commonly used to induce spinal cord LTF, this frequency exceeds the physiological firing range. Here, we examined the effects of electrical stimulation of the sciatic nerve within the physiological frequency range on the magnitude and stability of the C-fiber-evoked responses of wide dynamic range neurons and the expression of immediate early genes (c-fos, zif268, and Arc) in anesthetized rats. Stimulation frequencies of 3, 30 and 100 Hz all induced facilitation of similar magnitude as recorded at 1 h post-CS. Strikingly, however, 3 Hz-induced potentiation of the C-fiber responses was decremental, whereas both 30 and 100 Hz stimulation resulted in stable, non-decremental facilitation over 3 h of recording. The number of dorsal horn neurons expressing c-fos, but not zif268 or Arc, was significantly elevated after 3 Hz CS and increased proportionally with stimulation rate. In contrast, a stable LTF of C-fiber responses was obtained at 30 and 100 Hz CS, and at these frequencies there was a sharp increase in zif268 expression and appearance of Arc-positive neurons. The results show that response facilitation can be induced by stimulation frequencies in the physiological range (3 and 30 Hz). Three hertz stimulation induced the early phase of LTF, but the responses were decremental. Arc and zif268, two genes previously coupled to LTP of synaptic transmission in the adult brain, are upregulated at the same frequencies that give stable LTF (30 and 100 Hz). This frequency-dependence is important for understanding how the afferent firing pattern affects neuronal plasticity and nociception in the spinal dorsal horn.

  14. Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

    PubMed

    Patterson, T; Venables, P H

    1981-01-01

    Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

  15. Thermal detection thresholds of Aδ- and C-fibre afferents activated by brief CO2 laser pulses applied onto the human hairy skin.

    PubMed

    Churyukanov, Maxim; Plaghki, Léon; Legrain, Valéry; Mouraux, André

    2012-01-01

    Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2) laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

  16. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

    NASA Astrophysics Data System (ADS)

    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  17. Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents.

    PubMed

    Nobrega, Antonio C L; O'Leary, Donal; Silva, Bruno Moreira; Marongiu, Elisabetta; Piepoli, Massimo F; Crisafulli, Antonio

    2014-01-01

    During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed. PMID:24818143

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

    PubMed Central

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

    2016-01-01

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