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R L Snyder

Publications and source records attributed to R L Snyder.

At least 19 recordsLinked to original sources
PubMed1992

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Animals↗
PubMed1992

Chronic intracochlear electrical stimulation in neonatally deafened cats: effects of intensity and stimulating electrode location.

An earlier study conducted in this laboratory suggested that chronic intracochelear electrical stimulation at moderate current levels can at least partially delay or prevent the retrograde degeneration of primary auditory (spiral ganglion) neurons that otherwise is progressive after neonatal deafness induced by ototoxic drug administration. Increased survival of spiral ganglion neurons was observed within the basal cochlear region near the stimulating biopolar electrode pairs, while in more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this maintenance of spiral ganglion neurons induced by chronic electrical stimulation are uncertain, especially since increased neuronal survival was observed over broader sectors of the ganglion than would be expected to be directly activated by the bipolar electrodes and moderate stimulation intensity (6 dB above electrically evoked auditory brainstem response threshold) used. In this report, data are presented from a second series of neonatally deafened and chronically stimulated cats. The parameters for chronic electrical stimulation were manipulated in two simple ways. First, the intensity of the electrical stimulus was reduced from the earlier study, while the duration of chronic stimualtion periods was increased; and secondly, two different intracochlear positions of stimulating electrodes were employed in different experimental groups. Results indicate that elecrical stimulation of the cochlea at an extremely low intensity (2 dB above electrically evoked auditory brainstem response threshold) is sufficient to at least partially prevent or delay ganglion cell degeneration in the deafened cochlea. In addition, data suggest a differential distribution of the maintained or conserved ganglion cells, such that when the stimulating electrode pair was positioned near the base of the cochlea increased ganglion survival in a more basal cochlear sector, while stimulation at a more apical site resulted in increased neuronal survival extending to more apical regions.

Animals↗
PubMed1991

Chronic intracochlear electrical stimulation induces selective survival of spiral ganglion neurons in neonatally deafened cats.

Ten newborn kittens were deafened by systemic administration of neomycin sulfate. Profound hearing losses were documented by ABR and FFR (500 Hz) testing. At 9-17 weeks of age, the young deafened cats were unilaterally implanted with a multichannel scala tympani electrode. Six of the animals were chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 h/day for periods of 1 month or 3 months. Stimuli were charge-balanced biphasic pulses (200 microseconds/phase, 30 pps.) The remaining 4 cats underwent identical deafening and implantation schedules but were not stimulated. Results indicate that administration of neomycin in neonatal cats induced degeneration of hair cells and spiral ganglion cell loss that was bilaterally symmetrical between the two cochleas of each individual animal, although there was variation between animals in the severity of the ototoxic drug effect. In animals receiving passive (unstimulated) implants, morphometric analysis of spiral ganglion cell density showed no significant difference in ganglion cell survival between the implanted cochleas and the contralateral control ears. In contrast, animals that were chronically stimulated for 3 months showed significantly better neuronal survival in implanted and stimulated cochleas as compared to contralateral deafened control ears. The induced conservation of spiral ganglion neurons was observed consistently within the basal cochlear region near the stimulating electrodes. In more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this selective conservation of spiral ganglion neurons induced by chronic intracochlear electrical stimulation are uncertain. Since no comparable chronic stimulation studies have been conducted in adults, it is not known whether similar conservation effects could be induced in mature animals.

Animals↗
PubMed1991

Chronic intracochlear electrical stimulation in the neonatally deafened cat. II. Temporal properties of neurons in the inferior colliculus.

The major focus of this study was to define the effects of chronic intracochlear electrical stimulation (ICES) on single unit responses in the inferior colliculus from three experimental groups: 1) normal adults 2) neonatally-deafened/unstimulated adults; and 3) neonatally-deafened/chronically stimulated adults. The major findings include: 1) IC neurons in normal adults showed a diversity of perstimulus responses to ICES which were qualitatively similar to those evoked by acoustic stimuli. They responded with: an onset burst, a sustained discharge, a decrease in their spontaneous activity, or a strong post-stimulus response. The excitatory responses showed either a monotonic or a nonmonotonic increase in activity with increasing stimulus intensity. Response latencies ranged from 5 to over 40 ms. 2) Responses to ICES in normal and deafened/unstimulated animals were virtually indistinguishable from one another. 3) In contrast, responses to ICES in neonatally deafened stimulated animals were different from normal and from deafened, unstimulated animals. Their perstimulus response latencies were significantly shorter, their late response latencies were significantly longer, and the frequency of occurrence of inhibitory and late responses were significantly higher. From these results we conclude that the responses to intracochlear electrical stimulation are directly comparable to those observed following normal acoustic stimulation; that development of cochleotopic organization of the inferior colliculus is not affected by the almost complete lack of normal acoustic input experienced by neonatally deafened animals; and that the basic response properties of IC units are likewise unaffected by neonatal deafening. Moreover, the results suggest that, although the limited regime of electrical stimulation employed in these studies produced no major qualitative distortions in the perstimulus response patterns of IC neurons, it did result in some quantitative changes in those responses.

Animals↗
PubMed1991

Tinnitus suppression by cochlear implants.

The beneficial effects of cochlear implants on tinnitus have been noted in several studies, but few detailed appraisals of the phenomenon have been made. Six patients fitted with the UCSF/Storz cochlear implant device were studied. The effects of use of the implant device on tinnitus were monitored, and suppression of tinnitus was tracked throughout periods of stimulation and poststimulation. Tinnitus was effectively suppressed in five of six patients with the device on and with noise input, and reduction of perceived tinnitus loudness occurred in four of six with the device on but without acoustic input to the speech processor. Unilateral stimulation frequently resulted in bilateral tinnitus suppression. These studies reveal that profound tinnitus suppression is obtained by patients using their cochlear implants. Further work is required to quantify the optimal mode of stimulation, but these findings suggest that tinnitus sufferers may ultimately benefit from development of electrical stimulation tinnitus suppression devices.

Adult↗
PubMed1990

Chronic intracochlear electrical stimulation in the neonatally deafened cat. I: Expansion of central representation.

Intracochlear electrical stimulation via cochlear prostheses has been employed as a means of providing some hearing to deaf children. Since chronically restricted stimuli are known to have profound effects on central nervous system development, it is important to examine the effects of chronic intracochlear electrical stimulation in a neonatally deafened animal model. In this study neonatally deafened cats were implanted with a scala tympani electrode consisting of two pairs of electrodes. Chronic electrical stimulation was delivered using one electrode pair and consisted of charge-balanced biphasic pulses (200 microseconds/phase, 30 pps) at 2 dB above the electrically evoked auditory brain stem response (EABR) threshold for 4 h/day or at 6 dB 1 h/day, 5 days/week, for up to 3 months. The second electrode pair was unstimulated and served as an internal control. Following chronic stimulation, acute mapping experiments were performed in the central nucleus of the inferior colliculus (ICC) using single unit and multi-unit recording techniques and activating each electrode pair separately. In addition to these chronically stimulated animals, 2 other groups of experimental animals were studied: A normal group consisting of prior normal adult cats that were acutely implanted; and an unstimulated control group consisting of neonatally deafened adult cats that were either acutely implanted or implanted at 8-10 weeks of age but not chronically stimulated. Among the major findings of this study are: Electrical stimulation of the intracochlear bipolar electrode consistently produces activation of a reproducibly limited sector of the ICC. The location of this activated sector was found to be consistent with the known cochleotopic organization of the ICC and the intracochlear location of the stimulating electrodes. No major differences in the spatial representation of activated electrodes were found between prior normal cats and neonatally deafened unstimulated cats. The locations, shapes and widths of these spatial representations were virtually indistinguishable indicating that ICC cochleotopic organizations were equivalent in these two experimental groups. In contrast, the ICC representation of chronically stimulated electrode pairs were found to be significantly different. The average area activated by chronically stimulated electrode pairs at 6 dB above minimum threshold was approximately twice that of unstimulated deafened animals and prior normal animals; and it was larger, but not significantly so, than the average of the unstimulated electrode pair in the same experimental group.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1990

Intracytoplasmic neuronal inclusions in woodchuck brain stem.

Homogenous eosinophilic intracytoplasmic inclusion bodies were found within the large reticular neurons of the brain stems of 57 captive woodchucks (Marmota monax). Light microscopy was consistent with a proteinaceous nature, while electron microscopy suggested a non-viral origin. The woodchucks with inclusions were older than the general population that was studied. It is hypothesized that the neuronal inclusions in the brain stem are indicative of nonspecific ageing changes.

Aging↗
PubMed1989

Topographic organization of the central projections of the spiral ganglion in cats.

The morphological organization of inputs from restricted sectors of the cat cochlear spiral ganglion into the cochlear nucleus was studied by making focal extracellular injections of horseradish peroxidase (HRP) into the spiral ganglion. Injections resulted in Golgi-like labeling of a small cluster of spiral ganglion cells and their peripheral and central axons. Large injections involved most of the cells within Rosenthal's canal in sectors of the spiral ganglion innervating greater than or equal to 1 mm of the basilar membrane and resulted in narrow, complete laminae of labeled axons and preterminal fields within each cochlear nucleus subdivision. The positions of these bands were consistent with the "isofrequency laminae" appropriate for the frequencies represented at the injection sites, with high frequency laminae situated more dorsally, and lower frequencies progressively more ventral. A discrete projection to the small cell cap area was observed that was discontinuous with the main projection laminae in the ventral cochlear nuclei (VCN). In the dorsal cochlear nucleus, projecting fibers and terminals were excluded from the molecular cell layer. No labeled fibers entered the granule cell areas. In contrast to larger injections, very small HRP deposits labeled only part of an isofrequency lamina. Specifically, injections restricted to the scala tympani aspect of the spiral ganglion labeled only the lateral part of VCN isofrequency laminae, whereas injections limited to the scala vestibuli aspect of the ganglion labeled the medial aspect of the isofrequency planes. Thus these data indicate a previously unrecognized topographic representation of the vertical dimension of the spiral ganglion across VCN isofrequency laminae. Some possible functional implications of this projection organization are discussed.

Animals↗
PubMed1989

Characterization of the incorporation of woodchuck hepatitis virus surface antigen into hepatocyte plasma membrane in woodchuck hepatitis and in the virus-induced hepatocellular carcinoma.

Interaction between woodchuck hepatitis virus surface antigen and proteins of hepatocyte plasma membranes were examined in the course of woodchuck hepatitis virus infection. Membranes purified from animals with histologically confirmed acute hepatitis, active or persistent chronic hepatitis and the virus-related hepatocellular carcinoma were evaluated for the virus surface antigen contents, treated with agents eluting plasma membrane-bound antigen to test the extent of the antigen-membrane associations and incubated with purified, particulate woodchuck hepatitis virus surface antigen to determine membrane potential for the antigen adsorption. Hepatocyte plasma membranes originating from woodchucks chronically infected with the virus showed the highest quantities of the incorporated virus surface antigen among membranes studied, the behavior of bound antigen as an integral and a peripheral membrane protein and the resistance to bind an exogenous antigen. Similar properties were expressed by plasma membranes prepared from hepatocytes of nontumor parenchyma displaying chronic active hepatitis of a woodchuck hepatitis virus carrier with hepatoma. Furthermore, plasma membranes originating from animals with active or persistent chronic hepatitis demonstrated identical properties, implicating that histologic activity of the chronic liver inflammatory process is not dependent on the quantity of the virus surface antigen insertion into the membrane. In contrast, hepatocyte plasma membranes from animals with acute hepatitis showed significantly lower antigen quantities, presence of the antigen specificity exclusively behaving as an integral membrane protein and noticeable ability to bind an exogenous surface antigen of the virus. Comparable, but not identical, features were observed for hepatocyte membranes purified from nodules of hepatocellular carcinoma, suggesting that neoplastic transformation of infected hepatocytes is associated with loss of the membrane-bound antigen and with simultaneous, partial recovery of the membrane potential for the antigen binding. Comparative analysis of the properties on the woodchuck hepatitis virus surface antigen incorporation into hepatocyte plasma membranes in studied cases indicated that sustained infection with woodchuck hepatitis virus leads to an increase in the quantity of the membrane-incorporated antigen and to the appearance of the virus surface antigen specificity behaving as a peripheral membrane protein. In conclusion, this study demonstrated that the extent and the character of the antigen interaction with hepatocyte plasma membranes undergoes significant variations in the natural course of hepadna viral infect

Animals↗
PubMed1988

Intrinsic connections within and between cochlear nucleus subdivisions in cat.

The cat cochlear nuclear complex (CNC) is divided into three major subdivisions: the anteroventral, the posteroventral, and the dorsal cochlear nuclei (AVCN, PVCN, and DCN, respectively). Each of these subdivisions receives a topographic projection from the cochlea and each consists of a number of different cell types. The interconnections between these subdivisions and the cell types which give rise to them were studied by means of small injections of horseradish peroxidase (HRP) made at physiologically identified locations. DCN injections resulted in few labeled cells in the DCN, suggesting that its internal connections are very limited. In contrast, these same DCN injections resulted in numerous labeled cells in the PVCN and AVCN. Labeled PVCN cells, consisting of multipolar, octopus, and small spindle-shaped cells, were located in spatially restricted laminae stretching the entire rostrocaudal length of the nucleus, while labeled AVCN cells consisting of multipolar, globular, small spindle-shaped and small spherical cells were broadly distributed over the posterior half of the nucleus. Similar injections placed in the PVCN resulted in numerous labeled cells in all three subdivisions. The PVCN and AVCN cells labeled after PVCN injections were widely distributed across the isofrequency representations in both nuclei, while the labeled DCN cells were restricted to locations over the injection sites. Injections placed in the posterior half of the AVCN resulted in only very few labeled cells in the DCN. No cells were labeled following injections in the rostral AVCN.

Animals↗
PubMed1987

Uptake of horseradish peroxidase from perilymph by cochlear hair cells.

The specific mechanisms involved in the uptake of an exogenous protein, horseradish peroxidase (HRP), by cochlear hair cells were studied morphologically in light and electron microscopy. HRP was internalized by coated vesicles which formed from the plasma membrane only in the basal portion of the hair cells. Inner hair cells demonstrated relatively greater uptake than adjacent outer hair cells. The lateral plasma membrane of outer hair cells was unique in that reaction product was never bound to this portion of the membrane. Subsequent to endocytosis, HRP was transported to the Golgi and its associated system of endoplasmic reticulum and lysosomes. The exogenous protein was sequestered in a striking accumulation of secondary lysosomes and multivesicular bodies which were restricted to the infracuticular region of the hair cells and persisted for periods of at least 72 h after introduction of HRP. It is not clear whether the hair cells were slowly degrading the HRP or if the lysosomal enzymes necessary for its breakdown were lacking. The pathway demonstrated by HRP uptake and intracellular transport may represent one route by which macromolecules requisite for basic metabolic or nutritional requirements of the hair cells are supplied from the perilymph.

Animals↗
PubMed1987

Auditory neurophonic responses to amplitude-modulated tones: transfer functions and forward masking.

Two auditory neurophonic responses - one recorded from the scalp (frequency following response or FFR) and one from the auditory nerve (auditory nerve neurophonic or ANN) - were obtained following stimulation of the cat cochlea with amplitude-modulated (AM) high-frequency tones. The carrier frequencies varied between 2 and 30 kHz. The modulation frequencies varied between 400 and 3000 Hz. The AM responses were compared with pure-tone neurophonic responses. The AM response waveforms were found to have a similar spectral composition, similar rates of adaptation, and similar rates of recovery from forward masking as the comparable pure-tone responses. As with the pure-tone neurophonics, an unmodulated masking stimulus can produce prolonged depression of the probe response. The amount and duration of this depression is dependent upon the level and frequency of the masker. The frequency dependence of the depression is demonstrated by forward masked tuning curves which indicate that the AM responses arise from fiber populations which have restricted characteristic frequency distributions centered on the carrier frequency. Response amplitude as a function of stimulus level (I/O) functions, response amplitude as a function of carrier frequency (carrier transfer functions or CTF) and response amplitude as a function of modulation frequency (modulation transfer functions or MTF) were also measured. It was found that the I/O functions were saturating monotonic functions of stimulus intensity, CTFs were flat for carrier frequencies from 6 to 30 kHz, and MTFs were flat for modulation frequencies from 100 to 1500 Hz. These results are compared with similar data for single units and compound action potentials.

Acoustic Stimulation↗
PubMed1986

Effects of extracochlear direct current stimulation on the ensemble auditory nerve activity of cats.

The influence of direct current applied by round window stimulation on the whole nerve response of the auditory nerve of the cat has been studied. Effects on acoustically driven activity (CAP) and on the ensemble spontaneous activity of the nerve were observed. Stimulation with positive current suppressed driven and spontaneous activity. The strength and spread of suppressive effects was a function of the applied current level. After a period of positive electrical stimulation, driven and spontaneous activity rapidly returned to normal values. A rebound effect was sometimes observed, marked by a brief increase in spontaneous activity above the normal level. Negative current initially produced an increase in the amplitude of driven and spontaneous responses. Prolonged stimulation with negative current (greater than 30 s) resulted in a subsequent, graded reduction of neural activity, until a profound suppression of spontaneous and evoked neural activity was attained. The amplitude/latency relationship of CAPs was altered during passing of negative currents but not during passing of positive currents. Recovery from the suppression generated by negative currents was commonly prolonged for anything from a few seconds to many minutes; prolongation was dependent on stimulus amplitude, duration and duty cycles.

Acoustic Stimulation↗
PubMed1986

Identification and localization of pre-s-encoded polypeptides from woodchuck and ground squirrel hepatitis viruses.

A segment from the pre-s region of the woodchuck hepatitis virus (WHV) was inserted into an open reading frame vector allowing for the expression in Escherichia coli of viral determinants as part of a fusion protein. The bacterially synthesized fusion molecule contained eight amino acids from beta-galactosidase (beta-gal) at the N terminus, followed by 89 pre-s-encoded amino acids and 219 amino acids of chloramphenicol acetyltransferase (CAT) at the C terminus (beta-gal:pre-s:CAT). This tribrid protein was used to generate antiserum which had a significant titer to the viral portion of the fusion polypeptide. Anti-beta-gal:pre-s:CAT was used in Western blot analysis to identify viral proteins containing pre-s-encoded determinants. Antiserum to the tribrid molecule recognized four WHV polypeptides with molecular masses of 33, 36, 45, and 47 kilodaltons, each of which was also recognized by a monoclonal antibody to WHV surface antigen. Using the same anti-tribrid serum, we also identified analogous polypeptides from ground squirrel hepatitis virus. The antiserum was also used to immunoprecipitate virus particles containing endogenous DNA polymerase activity, indicating that pre-s determinants are found on the surface of mature virions. Based on previous computer studies and the location of pre-s-encoded molecules on the surface of virus particles, a role in hepadnavirus host cell entry is suggested for these polypeptides.

Animals↗
PubMed1986

Experimental infection of the woodchuck (Marmota monax monax) with woodchuck hepatitis virus.

Six woodchucks, 10 1/2 months of age, injected intramuscularly with 0.02 ml of woodchuck hepatitis virus (WHV)-positive serum and two woodchucks of similar age and origin injected with phosphate buffered saline were studied by serial blood samples and liver biopsy sections over an 18 week period. Serum samples were assayed for WHV surface antigen (WHsAg), its corresponding antibody (anti-WHs) and antibody to WHV core antigen (anti-WHc). WHV core antigen (WHcAg) was detected in liver biopsy sections by fluorescent labeled anti-WHc, and WHsAg was detected by the Victoria blue stain. All six experimentally infected woodchucks eventually developed anti-WHs and four developed serologic and histologic signs of acute hepatitis. Hepatic lesions resembled lesions described in the livers of chimpanzees and humans with acute hepatitis B viral infections. The first histologic signs of liver change coincided with the appearance of WHsAg within the serum and WHcAg within the cytoplasm of hepatocytes. After WHcAg was no longer detected in the serum, WHsAg appeared in the cytoplasm of hepatocytes. Microfocal areas of hepatic necrosis were associated with aggregates of lymphocytes, macrophages, and a few neutrophils and plasma cells. The periportal exudate became increasingly abundant during the 18-week study period in the four animals with acute hepatitis. The results from this study indicate that acute hepatitis may be induced in the woodchuck by experimental infection with WHV. Furthermore, the woodchuck might serve as an excellent model for the study of the pathogenesis of acute viral hepatitis in man.

Acute Disease↗
PubMed1986

Atrial fibrillation.

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Anti-Arrhythmia Agents↗