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Amino acid concentrations in rat cochlear nucleus and superior olive.

Distributions of 10 amino acids were mapped in the cochlear nucleus and superior olive of rats by microdissection of freeze-dried sections combined with high performance liquid chromatography. Glutamate concentrations were relatively high in regions containing granule cell bodies, axons and terminals, whereas aspartate concentrations were higher in the rest of the cochlear nucleus. The distribution of glutamine, a metabolic precursor of glutamate, correlated highly with that of glutamate. In the superior olive, glutamate concentrations were similar among the nuclei, whereas aspartate concentrations were higher in the more dorsal nuclei. Glycine concentrations were relatively high in dorsal portions of the cochlear nucleus and superior olive and were much higher in all regions than those of gamma-aminobutyrate (GABA). Both GABA and taurine showed decreasing gradients from superficial to deep layers of the dorsal cochlear nucleus. Concentrations of serine, threonine, arginine and alanine were generally lower than those of the other six amino acids. The results support other evidence for prominent roles of glutamate and glycine as neurotransmitters in the cochlear nucleus and superior olive. They support a neurotransmitter role also for GABA, especially in the superficial layers of the dorsal cochlear nucleus, but less in the superior olive. The literature related to our results is reviewed.

Amino Acids↗

Auditory experience affects degeneration of the ventral cochlear nucleus in Mongolian gerbils.

Gerbils exhibit a unique encephalopathy characterized by spongioform lesions in the neuropil of the cochlear nucleus and that others have recently described. The present results suggest that the course of this degenerative disorder is affected by acoustic experience. In gerbils in which acoustic stimulation was limited postnatally, the number and the extent of these lesions was dramatically reduced. Monaural deprivation reduced lesion number and extent only in the ipsilateral cochlear nucleus; binaural deprivation affected both cochlear nuclei. The lesions were most evident in certain portions of the cochlear nucleus, the caudal anterior ventral cochlear nucleus and the posterior ventral cochlear nucleus, sparing the rostral pole of the anterior ventral cochlear nucleus. In the affected regions the lesions were topologically restricted to the low and middle frequency regions. The apparent tonotopic distribution of lesions was associated with frequent exposure to low and middle frequency ambient noise.

Acoustic Stimulation↗

Identification of tuberculo-ventral neurons in the polymorphic layer of the rat dorsal cochlear nucleus.

The tuberculo-ventral tract represents a short nervous circuit within the auditory cochlear nuclei. Tuberculo-ventral neurons of the dorsal cochlear nucleus send isofrequency inhibitory inputs to bushy cells of the ventral cochlear nucleus. Injection of wheat germ agglutinin conjugated to horseradish peroxidase into the rat ventral cochlear nucleus, labelled tuberculo-ventral neurons retrogradely in the deep polymorphic layer of the ipsilateral dorsal cochlear nucleus. Five to 20% of the perimeter of these cells was covered by synaptic boutons, most of which contained flat and pleomorphic vesicles. These boutons contained glycine and sometimes GABA. Occasional small axo-somatic boutons contained round vesicles and were immunonegative for both glycine and GABA. This study shows that the synaptic profile of tuberculo-ventral neurons is different from that of other medium-size glycinergic neurons within the polymorphic layer or more superficial regions of the dorsal cochlear nucleus like cartwheel neurons. In fact the latter mostly receive boutons that contain pleomorphic vesicles.

Animals↗

Physiology and morphology of complex spiking neurons in the guinea pig dorsal cochlear nucleus.

Intracellular recordings from the dorsal cochlear nucleus have identified cells with both simple and complex action potential waveforms. We investigated the hypothesis that cartwheel cells are a specific cell type that generates complex action potentials, based on their analogous anatomical, developmental, and biochemical similarities to cerebellar Purkinje cells, which are known to discharge complex action potentials. Intracellular recordings were made from a brain slice preparation of the guinea pig dorsal cochlear nucleus. A subpopulation of cells discharged a series of two or three action potentials riding on a slow depolarization as an all-or-none event; this discharge pattern is called a complex spike or burst. These cells also exhibited anodal break bursts, anomalous rectification, subthreshold inward rectification, and frequent inhibitory postsynaptic potentials (IPSPs). Seven complex-spiking cells were stained with intracellular dyes and subsequently identified as cartwheel neurons. In contrast, six identified simple-spiking cells recorded in concurrent experiments were pyramidal cells. The cartwheel cell bodies reside in the lower part of layer 1 and the upper part of layer 2 of the nucleus. The cells are characterized by spiny dendrites penetrating the molecular layer, a lack of basal dendritic processes, and an axonal plexus invading layers 2 and 3, and the inner regions of layer 1. The cartwheel cell axons made putative synaptic contacts at the light microscopic level with pyramidal cells and small cells, including stellate cells, granule cells, and other cartwheel cells in layers 1 and 2. The axonal plexus of individual cartwheel cells suggests that they can inhibit cells receiving input from either the same or adjacent parallel fibers and that this inhibition is distributed along the isofrequency contours of the nucleus.

Action Potentials↗

The development and migration of large multipolar neurons into the cochlear nucleus of the North American opossum.

We have studied the maturation of the inferior colliculus and cochlear nuclei of the North American opossum with particular emphasis on the large multipolar neurons of the cochlear nucleus. These neurons include the principal and giant cells of the dorsal cochlear nucleus (DCN) and the large neurons of the ventral cochlear nucleus (VCN), all of which can be labelled by horseradish peroxidase (HRP) injections into the contralateral inferior colliculus (IC). The size of these neurons, their characteristic Nissl patterns, and their labelling density after injections into the IC render them distinguishable from other neurons in this nuclei, even in young animals. In Nissl-stained sections of newborn opossums, a band of horizontally oriented neurons can be identified dorsomedial to the vestibular nerve root. This band extends from an apparent cytogenetic zone close to the sulcus limitans, to, but not within, the presumptive cochlear nucleus. Between birth and estimated postnatal day 22 (EPND 22) the band shifts laterally, eventually becoming incorporated into the cochlear nucleus. Many neurons in this band have perinuclear caps of Nissl substance similar to those present in the principal cells of the adult DCN. Injections of HRP into the IC as early as EPND 5 (17 days after conception) labelled neurons in the band referred to above but not in the presumptive cochlear nucleus. By EPND 15, labelled cells were clustered mainly within the nucleus proper. Most of these cells were located in the DCN, but a few were scattered in the dorsocentral VCN. Consistent labelling of small neurons in VCN was not obtained until sometime later. From EPND 15 to EPND 20 most of the labelled cells in DCN reoriented in the vertical plane, aligned in layer II, and differentiated into principal neurons. Some, however, remained deep to layer II and differentiated into giant neurons. The heavily labelled cells in VCN differentiated into large neurons. Our results suggest that the large multipolar neurons of the nucleus are generated in a cytogenetic zone medial to the rhombic lip and that they subsequently migrate laterally, in a band, to reach their adult locations in the nucleus. It is during this migratory stage that their axons reach the inferior colliculus.

Animals↗

Purkinje-like cells in rat cochlear nucleus.

A unique class of cells, strongly immunopositive for anti-calbindin D-28 kDa was observed in and near the cochlear nucleus of young adult, male Sprague-Dawley rats. These cells are present in small numbers which are highly variable across animals and inconstant in position. They are preferentially located in the dorsal cochlear nucleus, with occasional examples being present in the ventral cochlear nucleus, as well as in adjacent brainstem locations. They have been referred to in other studies as displaced Purkinje cells or 'Purkinje cell-like cells', and are here designated 'Purkinje-like cells' (PLCs). PLCs have relatively large cell bodies, with thick, heavily spined dendrites, and are typically situated in an immediately subpial position. The dendritic arborization extends into the interior of the nucleus, away from the pial surface, a trajectory opposite in direction to that of the cerebellar Purkinje cells. The intense immunoreactivity exhibited by PLC somata and dendrites when treated with antiserum directed against calbindin is equivalent to that of cerebellar Purkinje cells, and markedly stronger than that of most other cell populations of the cochlear nucleus. However, in tissue treated with anti-parvalbumin, which also strongly labels cerebellar Purkinje cell somata and dendrites, PLC labeling, when present, is relatively weak, limited to the cell bodies and only the base of the dendrites of PLCs, indicating non-equivalence of the two cell types. In addition, the intensity of calbindin immunostaining in the PLCs appears to be more sensitive to glutaraldehyde in any of the fixative solutions than that seen in cerebellar Purkinje cells in the same sections. Of the cell types of the cochlear nucleus, the cartwheel cells would appear to be the most similar to the PLCs on morphological and immunocytochemical grounds. However, the subpial position and average somal dimensions of the PLCs, as well as the relatively modest immunoreactivity of the cartwheel cells for calbindin, rather clearly differentiate the PLCs from this class of neurons. The results of the present study suggest that the PLCs of the cochlear nucleus, although they may arise developmentally as ectopic cerebellar Purkinje cells and maintain certain Purkinje cell characteristics, represent a distinct neuronal cell type in the adult rat cochlear nucleus, exhibiting incomplete overlap of fixation, immunocytochemical and morphological characteristics with both cartwheel cells of the cochlear nucleus and cerebellar Purkinje cells.

Animals↗

Distribution of GABAA and GABAB binding sites in the cochlear nucleus of the guinea pig.

We compared the distribution of GABAA and GABAB binding sites in the cochlear nucleus using quantitative receptor autoradiography with [3H]GABA. To visualize GABAA binding sites, GABAB binding sites were blocked with +/- baclofen. To visualize GABAB binding sites, isoguvacine was used to block GABAA binding sites. GABAA binding sites predominated over GABAB, although there were marked regional differences in the distribution of binding. In the ventral cochlear nucleus, GABAA and GABAB binding sites were concentrated in the peripheral granule cell cap, with low binding levels in the central region. In the dorsal cochlear nucleus, binding was concentrated in the superficial (fusiform and molecular) layers, with a distinct laminar pattern. GABAA binding sites predominated in the fusiform cell layer. The molecular layer contained the highest level of GABAB binding sites in the entire cochlear nucleus. These results suggest that GABAergic inhibition in the cochlear nucleus is mediated both by GABAA and GABAB receptors, particularly in the dorsal cochlear nucleus. However, low levels of binding in areas such as the magnocellular regions of the ventral cochlear nucleus, known to contain abundant GABAergic synapses, suggest heterogeneity of GABA receptors in this auditory nucleus.

Animals↗

Impaired morphological development of the dorsal cochlear nucleus in hamsters treated postnatally with alpha-difluoromethylornithine.

The dorsal cochlear nucleus is a highly organized nucleus in the auditory system in which the ramifications of depletion of specific cell types during development can be studied. Granule cells, small interneurons that are located in all layers of the DCN in the adult hamster, proliferate postnatally and are, therefore, potentially vulnerable to anti-mitotic agents that are administered after birth. The present experiments describe the effects of alpha-difluoromethylornithine, a drug that inhibits proliferation of cerebellar granule cells, on the granule cells in the dorsal cochlear nucleus. As in the cerebellum, the density of granule cells in the dorsal cochlear nucleus is reduced after alpha-difluoromethylornithine treatment. In hamsters treated with alpha-difluoromethylornithine (200 or 500 mg/kg subcutaneously (s.c.), twice daily on postnatal days 4-14), the numerical density of granule cells was reduced in the superficial dorsal cochlear nucleus at 15 days; by 40 days this effect was also apparent in the deep layer, suggesting that cells located superficially that would have migrated into the deep dorsal cochlear nucleus had either failed to develop or did not arrive at their final location. This evidence suggests that the cells normally migrate down from the superficial proliferative zone into the deeper layers. In the drug-treated animals, a layer of mixed granule cells and fusiform cells was thinner than in controls probably due to the reduction in interspersed granule cells since the number of fusiform cells was unaffected. There was also a dose-dependent effect on cell growth; fusiform cells were affected at both doses, while giant cells were only affected at the highest dose. Granule cells form a major input to the fusiform cells and their depletion may account for some of the effects on fusiform cell growth. There could also be additional direct actions of alpha-difluoromethylornithine on this population.

Age Factors↗

Effects of carboplatin on amino acid chemistry in chinchilla cochlear nucleus.

Carboplatin, a drug widely used against solid head and neck tumors, selectively destroys cochlear inner hair cells and type I auditory nerve fibers in chinchilla. This should affect neurotransmitter chemistry, involving amino acids, where the type I auditory nerve fibers terminate in the cochlear nucleus. Using microdissection combined with high-performance liquid chromatography, amino acid concentrations were mapped in the cochlear nuclei of chinchillas injected intraperitoneally 6-8 weeks earlier with 100 mg/kg carboplatin and in those of control animals. Glutamate concentrations were 23% lower in the anteroventral cochlear nucleus (AVCN) and 40% lower in the posteroventral cochlear nucleus (PVCN) of carboplatin-injected chinchillas as compared to controls, while aspartate concentrations were 18% lower in AVCN and 27% lower in PVCN. Using a fluorometric assay, activities of glutaminase, an enzyme which catalyzes glutamate synthesis, were 30% lower in AVCN and 38% lower in PVCN of carboplatin-injected chinchillas. Concentrations of glutamine, gamma-aminobutyrate, and glycine were also lower in some ventral and dorsal cochlear nucleus regions of treated animals. These changes probably result mainly from both primary and later effects of reduced type I auditory nerve fiber input to the cochlear nucleus.

Amino Acids↗

Ultrastructural and immunocytochemical characterization of commissural neurons in the ventral cochlear nucleus of the rat.

Medium to large-giant multipolar neurons in the rat ventral cochlear nucleus were retrograde labelled after injection of the tracer Wheat Germ Agglutinin conjugated to Horse Radish Peroxidase into the contralateral cochlear nucleus. Light microscopy immunocytochemistry showed that 42.45% of these retrograde labelled neurons, generally strongly labelled with the tracer, were markedly glycine immunopositive, and that 57.55%, usually weakly retrograde labelled neurons, were immunonegative or weakly positive for glycine. These commissural neurons were generally GABA negative and variably immunopositive for glutamate. About 1/3rd of the commissural neurons had variably developed a rough endoplasmic reticulum whilst axo-somatic boutons covered 20-40% of the cell body. These cells were recognized as multipolar neurons of type I. Most of them were weakly glycine positive or even negative and a few appeared glycinergic. A little less than the remaining 2/3rds of the whole commissural population in the postero-ventral cochlear nucleus presented a surface which was 65-85% covered with synaptic boutons, among which some also appeared labelled. These cells were recognized as multipolar neurons of type II. Many microtubules and neurofilaments were present, free ribosomes being more numerous around Nissl bodies with short cisternae. A few low retrograde labelled type II were weakly or non glycinergic. A small number of large to giant neurons type II, strongly retrograde labelled, appeared to be glycine positive, consistently GABA negative and variably glutamate positive. A very small proportion of retrograde labelled neurons appeared having the characteristics of globular bushy neurons. Their weak labelling, however, suggests that they project by collaterals or thin axons to the contralateral cochlear nucleus. Spherical bushy cells in the rat anteroventral cochlear nucleus lack the nuclear capping of rough endoplasmic reticulum observed in the cat, and none was labelled after injection into the contralateral cochlear nucleus. Globular and spherical neurons were variably glutamate positive but glycine and GABA negative. In conclusion, the present study suggests that commissural neurons include a small number of strongly labelled large to giant glycinergic and presumably inhibitory type II and, less frequently type I. A large group of less heavily labelled commissural neurons of type I and II contain low levels or no glycine, which is probably used for metabolic purposes rather than as a neurotransmitter. This suggests that these neurons are presumably excitatory.

Actin Cytoskeleton↗

Tuberculoventral neurons project to the multipolar cell area but not to the octopus cell area of the posteroventral cochlear nucleus.

Tuberculoventral neurons in the deep layer of the dorsal cochlear nucleus (DCN) provide frequency-specific inhibition to neurons in the anteroventral cochlear nucleus (AVCN) of the mouse (Wickesberg and Oertel, '88, '90). The present experiments examine the projection from the deep DCN to the posteroventral cochlear nucleus (PVCN). Horseradish peroxidase (HRP) injections into the PVCN reveal that the multipolar cell area, but not the octopus cell area, is innervated by neurons in the deep layer of the DCN. Injections into the multipolar cell area, in the rostral and ventral PVCN, labeled neurons across the entire rostrocaudal extent of the deep DCN. The labeled tuberculoventral neurons generally lay within the band of labeled auditory nerve terminals in the DCN. Injections of HRP into the octopus cell area, in the dorsal caudal PVCN, labeled almost no cells within the band of auditory nerve fiber terminals that were labeled by the same injection. The inhibition from tuberculoventral neurons onto ventral cochlear nucleus (VCN) neurons is likely to be mediated by glycine (Wickesberg and Oertel, '90). Slices of the cochlear nuclear complex were immunolabeled by an antibody against glycine conjugated with glutaraldehyde to bovine serum albumin (Wenthold et al., '87). Glycine-like immunoreactivity was found throughout the DCN, the AVCN and the multipolar cell area, but there was little labeling in the octopus cell area. This finding provides independent evidence that tuberculoventral neurons do not innervate the octopus cell area and indicates that the octopus cell area is anatomically and functionally distinct.

Animals↗

Structural and functional classes of multipolar cells in the ventral cochlear nucleus.

Multipolar cells in the ventral cochlear nucleus (VCN) are a structurally and functionally diverse group of projection neurons. Understanding their role in the ascending pathway involves partitioning multipolar cells into distinct populations and determining where in the brain each sends its coded messages. In this study, we used retrograde labeling techniques in rats to identify multipolar neurons that project their axons to the ipsilateral dorsal cochlear nucleus (DCN), the contralateral CN, or both structures. Three rats received injections of biotinylated dextran amine in the ipsilateral DCN and diamidino yellow in the contralateral CN. Several radiate multipolar neurons (defined by their axonal projections to the ipsilateral DCN and their dendrites that traverse VCN isofrequency sheets) were double-labeled but over 70% were not. This result suggests two distinct populations: (1) radiate-commissural (RC) multipolar cells that project to the ipsilateral DCN and the contralateral CN, and (2) radiate multipolar cells that project exclusively (in this context) to the ipsilateral DCN. In a different group of animals, we retrogradely labeled multipolar neurons that project their axons to the contralateral CN and measured the size of their cell bodies. The mean size of this population (266 +/- 156 microm2) was significantly smaller than those of RC-multipolar cells (418 +/- 140 microm2). We conclude that the CN commissural pathway is composed of at least two components: (1) RC multipolar cells and (2) commissural multipolar cells that are small- and medium-sized neurons that project exclusively (in this context) to the contralateral CN. These results identify separate structural groups of multipolar cells that may correspond to physiological unit types described in the literature. They also provide protocols for isolating and studying different populations of multipolar cells to determine the neural mechanisms that govern their responses to sound.

Amidines↗

Glycine immunoreactivity localized in the cochlear nucleus and superior olivary complex.

Polyclonal antibodies were made in rabbits against glycine conjugated to bovine serum albumin with glutaraldehyde and were used for immunocytochemical studies in the cochlear nucleus and superior olivary nucleus of the guinea-pig. Antibodies selective for glycine were prepared by affinity chromatography. By dot-blot analysis this preparation showed a strong recognition of glycine conjugates and relatively little recognition of conjugates of most other amino acids tested. However, there was a significant reaction with conjugates of alanine and beta-alanine, and this cross-reaction could not be removed by affinity chromatography without eliminating the preparation's recognition of glycine. The affinity-purified preparation showed only a weak recognition of conjugates of gamma-aminobutyrate (GABA) which was detectable at high concentrations of primary antibody. Immunocytochemical studies showed several intensely staining cell bodies in the cochlear nucleus and superior olivary complex. Most immunoreactive cell bodies in the cochlear nucleus were in the dorsal cochlear nucleus, being present in both the superficial and deep layers. Scattered immunoreactive cells were present in the ventral cochlear nucleus. Intense staining of cell bodies was seen in the medial nucleus of the trapezoid body, and these cells appear to correspond to the principal cells of that nucleus. Punctate labelling, suggestive of immunoreactive presynaptic terminals, was also apparent, particularly in the ventral cochlear nucleus and lateral superior olive. In the ventral cochlear nucleus, immunoreactive puncta were found around unlabeled cell bodies, at times nearly covering the perimeter of the cell. A population of glycine-immunoreactive cell bodies in the superficial dorsal cochlear nucleus also labeled with anti-GABA antibodies as determined through double-labeling studies. However, glycine-positive cells in the deep dorsal cochlear nucleus were not labeled with anti-GABA antibodies, and some populations of GABA-positive cells in the superficial layers were not labeled with anti-glycine antibodies. In the hippocampus intense staining of cell bodies and puncta was seen with anti-GABA antibodies while essentially no staining was seen with anti-glycine antibodies. These results suggest that anti-glycine antibodies can be useful for immunocytochemical identification of glycinergic neurons. From this study several populations of putative glycinergic neurons are identified in the auditory nuclei of the brain stem using these antibodies. Some populations of GABA-containing neurons also contain high levels of glycine or a related molecule.

Animals↗

Projections from the superior olivary complex to the cochlear nucleus in the tree shrew.

The origins and targets of projections from the superior olivary complex to the cochlear nuclei were studied in the tree shrew by placing small injections of horseradish peroxidase (HRP) in the cochlear nucleus and small injections of 3H-leucine in the superior olivary complex. The results show that the descending pathways originate in periolivary cell groups surrounding the medial and lateral superior olives and that periolivary nuclei differ from one another in their patterns of projections to the cochlear nucleus. For example, cell groups may project either ipsilaterally or bilaterally. Cells in the lateral nucleus of the trapezoid body project only to the ipsilateral cochlear nucleus. Other periolivary cell groups project bilaterally, although some of these may project more heavily to one side than the other. Some pathways have widespread targets in the cochlear nucleus whereas others have relatively specific targets. Diffuse projections to all divisions of the cochlear nucleus arise from the lateral nucleus of the trapezoid body ipsilaterally and from the medial perioliviary nucleus bilaterally. The targets of other descending pathways are more restricted. The anterolateral, dorsal, and dorsolateral periolivary nuclei project mainly to the anteroventral cochlear nucleus; the ventral nucleus of the trapezoid body and the posterior periolivary nucleus project mainly to the dorsal and posteroventral cochlear nuclei. All of these specific projections are bilateral. These results suggest that projections from the periolivary cell groups to the cochlear nucleus consist of multiple components with different degrees of specificity.

Animals↗

Projections from the anteroventral cochlear nucleus to the lateral and medial superior olivary nuclei.

The projections from the cochlear nucleus to the lateral and medial superior olivary nuclei were studied in the cat by use of retrograde transport of horseradish peroxidase to demonstrate the connections. The medial superior olivary nucleus receives input only from the anterior and posterodorsal subdivisions of the anterior division of the anteroventral cochlear nucleus (AA and APD, respectively; Brawer, Morest, and Kane: J. Comp. Neurol. 155: 251-300, 1974). These two subdivisions are populated almost exclusively by spherical bushy cells. Like the medial superior olivary nucleus, the lateral superior olivary nucleus receives inputs from AA and APD. In addition, the lateral superior olivary nucleus receives projections from the posterior subdivision (AP) of the anterior division and also from the posterior division of the anteroventral cochlear nucleus. The projections to the medial superior olivary nucleus are bilateral, whereas the projections to the lateral superior olivary nucleus are almost entirely ipsilateral. One implication of the results is that the medial superior olivary nucleus receives inputs from only one cell type--the spherical bushy cell--but that, at the least, two cell types project to the lateral superior olivary nucleus. Both the olivary nuclei receive input from most, if not all, of the dorsoventral extent of the anteroventral cochlear nucleus, implying that both receive input from neurons arrayed across the entire frequency representation of the anteroventral cochlear nucleus. All of the projections appear to be organized topographically such that frequency representation is preserved.

Animals↗

Cytoarchitectonic atlas of the cochlear nucleus of the chinchilla, Chinchilla laniger.

A detailed cytoarchitectonic atlas of the chinchilla cochlear nucleus complex was prepared in the transverse plane with the Nissl method. Subdivisions of the cochlear nucleus were defined on the basis of cell size, cell packing density, and, in some cases, on cytological features of cell types. In general, the chinchilla cochlear nucleus has an organizational plan similar to that described for other mammalian species. As in other rodents, the chinchilla has a large and well-developed dorsal cochlear nucleus consisting of three distinct layers. The ventral cochlear nucleus consists of two distinct nuclear masses, a posterior nuclear group and an anterior nuclear group, each composed of several subdivisions, which are qualitatively similar to those described for other mammals. Thus it is now possible to compare detailed observations, such as tonotopic maps, in the chinchilla with findings from the analogous cell populations in other mammals, such as the cat, with considerable precision. In the chinchilla, three cell groups, previously undescribed in mammals, have been defined and their counterparts in the cat identified.

Animals↗

Glycine immunoreactivity and receptor binding in the cochlear nucleus of C57BL/6J and CBA/CaJ mice: effects of cochlear impairment and aging.

Glycinergic neurons in the cochlear nucleus (CN) of C57BL/6J (C57) and CBA/CaJ (CBA) mice were studied by using immunocytochemical and receptor-binding techniques. Adult C57 mice exhibit progressive cochlear pathology as they age, whereas aging CBA mice retain good hearing. In the CN of old C57 mice (18 months) with severe hearing loss, the number of glycine-immunoreactive neurons decreased significantly. The number (Bmax) of strychnine-sensitive glycine receptors (GlyR) decreased significantly in the dorsal CN of old C57 mice. Significant effects were not observed in the CN of middle-aged C57 mice (with less-severe hearing loss) or in very old CBA mice (which do not exhibit severe hearing loss). The data suggest that the combination of severe hearing loss and old age results in deficits in one or more inhibitory glycinergic circuits in the CN.

Aging↗

The representation of steady-state vowel sounds in the temporal discharge patterns of the guinea pig cochlear nerve and primarylike cochlear nucleus neurons.

We have recorded the responses of fibers in the cochlear nerve and cells in the cochlear nucleus of the anesthetized guinea pig to synthetic vowels [i], [a], and [u] at 60 and 80 dB SPL. Histograms synchronized to the pitch period of the vowel were constructed, and locking of the discharge to individual harmonics was estimated from these by Fourier transformation. In cochlear nerve fibers from the guinea pig, the responses were similar in all respects to those previously described for the cat. In particular, the average-localized-synchronized-rate functions (ALSR), computed from pooled data, had well-defined peaks corresponding to the formant frequencies of the three vowels at both sound levels. Analysis of the components dominating the discharge could also be used to determine the voice pitch and the frequency of the first formants. We have computed similar population measures over a sample of primarylike cochlear nucleus neurons. In these primarylike cochlear nucleus cell responses, the locking to the higher-frequency formants of the vowels is weaker than in the nerve. This results in a severe degradation of the peaks in the ALSR function at the second and third formant frequencies at least for [i] and [u]. This result is somewhat surprising in light of the reports that primarylike cochlear nucleus cells phaselock, as well as do cochlear nerve fibers.

Animals↗