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.     

Quantitative analysis of spiral ganglion projections to the cat cochlear nucleus

A quantitative examination of the tonotopic organization of primary afferent projections to the cochlear nucleus (CN) in adult cats wasconducted by using focal extracellular injections of Neurobiotin (NB) into the spiral ganglion of the basal cochlea. One to three injections separated by intervals of at least 2 mm were positioned along the basal one-third of the cochlea. Each injection produced discrete projection laminae that appeared as parallel horizontal sheets of labeled axons and terminals distributed sequentially dorsally to ventrally across each major CN subdivision: the anteroventral, posteroventral, and dorsal cochlear nucleus (AVCN, PVCN, and DCN, respectively). The length (rostrocaudal dimension), width (mediolateral dimension), thickness (dorsoventral dimension), and relative placement of 18 “frequency-band” laminae were measured in 10 adult cochlear nuclei. The average AVCN projection thickness was approximately twice that of the PVCN and DCN projections. In double injection cases, the center-to-center separation between AVCN laminae was also approximately twice that in the PVCN and equal to that in the DCN. Lamina thickness did not differ significantly as a function of frequency representation. However, in both width and length, mid-frequency laminae were up to two times larger than high-frequency laminae. Thus, the results indicate that DCN projections are the most discrete (i.e., are the thinnest and have the least overlap between adjacent frequency projections), whereas the AVCN projections are the largest but are as discrete as PVCN projections. In addition, high-frequency projections are smaller and more discrete than mid-frequency projections, which are larger and have greater overlap with adjacent frequency projections. J. Comp. Neurol. 379:133-149, 1997. © 1997 Wiley-Liss, Inc.     

Development of the cochlear innervation of the dorsal cochlear nucleus of the hamster

The development of cochlear fibers and terminals in the dorsal cochlear nucleus of the hamster was studied with light and electron microscopic techniques. Like the dorsal cochlear nucleus of most other mammals, the dorsal cochlear nucleus of the adult hamster is a laminated structure. Three distinct layers can be identified in cresyl-violet-stained sections: the molecular layer, the fusiform cell layer, and the deep layer. The deep layer consists of a superficial zone, free of large cell bodies, and a deep zone which contains the somas of giant cells. Horseradish peroxidase and degeneration studies reveal that the cochlear fibers ramify throughout the deep and fusiform cell layers of the adult hamster but do not enter the molecular layer. In the electron microscope, three types of terminals that contact the fusiform and the giant cells can be distinguished. Only one type of terminal (type LR) degenerates after cochlear ablation and is, therefore, thought to be of cochlear origin. Type LR terminals are found throughout the deep and fusiform cell layers and contact the somas of giant and fusiform cells, as well as their intermingled dendrites in the deep layer. In Golgi-impregnated material, cochlear fibers are not found in the dorsal cochlear nucleus of the neonatal hamster, although they have entered the ventral cochlear nucleus. Ingrowth of cochlear fibers into the dorsal cochlear nucleus occurs over the first postnatal week and one-half. A spatial gradient is evident during the ingrowth of the fibers in that they invade the dorsomedial parts of the dorsal cochlear nucleus before they invade the ventrolateral parts. In all parts of the nucleus, the fibers enter the deepest layer and grow progressively more superficially. In the electron microscope, the first appearance of type LR terminals at each depth lags behind the ingrowth of the fibers by about two days. In hamsters, fibers from the basal turns of the cochlea terminate in the dorsomedial dorsal cochlear nucleus, while fibers from the apical turns terminate in the ventrolateral dorsal cochlear nucleus (DCN). The dorsomedial to ventrolateral gradient in the ingrowth of the cochlear fibers into the DCN indicates that the fibers from the basal turn are the first to arrive. Several components of the mammalian cochlea have been shown to mature at the base of the cochlea before they mature at the apex. The present study suggests that maturation gradients in the cochlear nucleus parallel those observed in the cochlea.     

Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats

Studies of visual system development have suggested that competition driven by activity is essential for refinement of initial topographically diffuse neuronal projections into their precise adult patterns. This has led to the assertion that this process may shape development of topographic connections throughout the nervous system. Because the cat auditory system is very immature at birth, with auditory nerve neurons initially exhibiting very low or no spontaneous activity, we hypothesized that the auditory nerve fibers might initially form topographically broad projections within the cochlear nuclei (CN), which later would become topographically precise at the time when adult-like frequency selectivity develops. In this study, we made restricted injections of Neurobiotin, which labeled small sectors (300-500 microm) of the cochlear spiral ganglion, to study the projections of auditory nerve fibers representing a narrow band of frequencies. Results showed that projections from the basal cochlea to the CN are tonotopically organized in neonates, many days before the onset of functional hearing and even prior to the development of spontaneous activity in the auditory nerve. However, results also demonstrated that significant refinement of the topographic specificity of the primary afferent axons of the auditory nerve occurs in late gestation or early postnatal development. Projections to all three subdivisions of the CN exhibit clear tonotopic organization at or before birth, but the topographic restriction of fibers into frequency band laminae is significantly less precise in perinatal kittens than in adult cats. Two injections spaced > or = 2 mm apart in the cochlea resulted in labeled bands of projecting axons in the anteroventral CN that were 53% broader than would be expected if they were proportional to those in adults, and the two projections were incompletely segregated in the youngest animals studied. Posteroventral CN (PVCN) projections (normalized for CN size) were 36% broader in neonates than in adults, and projections from double injections in the youngest subjects were nearly fused in the PVCN. Projections to the dorsal division of the CN were 32% broader in neonates than in adults when normalized, but the dorsal CN projections were always discrete, even at the earliest ages studied.     

Absence of plasticity of the frequency map in dorsal cochlear nucleus of adult cats after unilateral partial cochlear lesions

In adult animals, lesions to parts of the auditory receptor organ, the cochlea, can produce plasticity of the topographic (cochleotopic) frequency map in primary auditory cortex and a restricted or patchy plasticity in the auditory midbrain. This effect is similar to the plasticity of topographic maps of the sensory surface seen in visual and somatosensory cortices after restricted damage to the appropriate receptor surface in these sensory systems. There is dispute about the extent to which subcortical effects contribute to cortical plasticity. Here, we have examined whether topographic map plasticity similar to that seen in the auditory cortex and the midbrain is observed in the adult auditory brainstem. When partial cochlear lesions were produced in the same manner as those that were produced in the cortex and midbrain studies, we found no plasticity of the frequency map in the dorsal cochlear nucleus (DCN). Small regions of the DCN that were deprived of their normal, most sensitive frequency (characteristic frequency; CF) input by the cochlear lesion appeared to have acquired new CFs at frequencies at or near the edge of the cochlear lesion. However, examination of thresholds at the new CFs established that the changes simply reflected the residue of prelesion input to those sites: The patterns of CF thresholds were very well predicted by simple calculations of the patterns that were expected from such residual input. The results of this study suggest that the DCN does not exhibit the type of plasticity that has been found in the auditory cortex and midbrain; therefore, it does not account for the changes in responsiveness observed in the higher level structures under similar experimental conditions. J. Comp. Neurol. 399:35–46, 1998. © 1998 Wiley-Liss, Inc.     

Effect of altered neuronal activity on cell size in the medial nucleus of the trapezoid body and ventral cochlear nucleus of the gerbil

Activity-dependent transneuronal regulation of neuronal soma size has been studied in the medial nucleus of the trapezoid body and ventral cochlear nucleus of adolescent gerbils. Cochlear ablation or tetrodotoxin has been used to eliminate afferent electrical activity in auditory nerve fibers permanently or for 24 or 48 hours. Previous studies have shown that the cross-sectional area of spherical cell somata in the ipsilateral anteroventral cochlear nucleus decreases within 24 hours of electrical activity blockade with tetrodotoxin, which is fully reversible when activity is restored. The present findings extend this work by directly comparing the results of unilateral blockade of auditory nerve action potentials or unilateral cochlear ablation on the size of spherical and globular cell bodies in the ventral cochlear nucleus with changes produced by the same manipulations in third-order cells, principal neurons in the medial nucleus of the trapezoid body. Soma size in both ventral cochlear nucleus cell types decreases reliably by 24 hours after cochlear removal or eighth nerve activity blockade by tetrodotoxin. Soma size of neurons in the contralateral medial nucleus of the trapezoid body decreases 48 hours, but not 24 hours, after either manipulation. When activity in auditory nerve fibers is allowed to resume for 7 days following a 48-hour activity blockade, soma size fully recovers in the medial nucleus of the trapezoid body as well as in ventral cochlear nucleus neurons. We also report that the cross-sectional area of neuronal soma in the medial nucleus of the trapezoid body is larger in lateral regions of medial nucleus of the trapezoid body (low-frequency representation) than in the medial regions of the nucleus (high-frequency representation). We conclude that cell body size changes in brainstem auditory neurons are reversible and that the signals associated with the loss and subsequent recovery of soma size are activity related. However, the delayed effect of activity deprivation in the medial nucleus of the trapezoid body suggests that trophic substances released by afferent axons may contribute to the maintenance of anatomical characteristics. © 1994 Wiley-Liss, Inc.     

Neonatal deafness results in degraded topographic specificity of auditory nerve projections to the cochlear nucleus in cats

We previously examined the early postnatal maturation of the primary afferent auditory nerve projections from the cat cochlear spiral ganglion (SG) to the cochlear nucleus (CN). In normal kittens these projections exhibit clear cochleotopic organization before birth, but quantitative data showed that their topographic specificity is less precise in perinatal kittens than in adults. Normalized for CN size, projections to the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) subdivisions are all significantly broader in neonates than in adults. By 6-7 postnatal days, projections are proportionate to those of adults, suggesting that significant refinement occurs during the early postnatal period. The present study examined SG projections to the CN in adult cats deafened as neonates by ototoxic drug administration. The fundamental organization of the SG-to-CN projections into frequency band laminae is clearly evident despite severe auditory deprivation from birth. However, when normalized for the smaller CN size in deafened animals, projections are disproportionately broader than in controls; AVCN, PVCN, and DCN projections are 39, 26, and 48% broader, respectively, than predicted if they were precisely proportionate to projections in normal hearing animals. These findings suggest that normal auditory experience and neural activity are essential for the early postnatal development (or subsequent maintenance) of the topographic precision of SG-to-CN projections. After early deafness, the basic cochleotopic organization of the CN is established and maintained into adulthood, but the CN is severely reduced in size and the topographic specificity of primary afferent projections that underlies frequency resolution in the normal central auditory system is significantly degraded.     

Morphology and physiology of cells in slice preparations of the dorsal cochlear nucleus of mice

Horseradish peroxidase (HRP) was injected into cells from which intracellular recordings were made in slices of the dorsal cochlear nucleus (DCN) in order to correlate physiology with morphology. In general, the morphology of cells labeled intracellularly with HRP corresponded to those made with Golgi impregnations in mice and other mammals. The following cells were labeled: one granule cell, four cartwheel cells, eight fusiform cells, two other cells in the fusiform cell layer, and two tuberculoventral association cells in the deep layers of the DCN. The axon of the granule cell runs parallel to isofrequency laminae with collaterals branching perpendicularly and running along the tonotopic axis. The cartwheel cells have dendrites in the molecular layer that are densely covered with spines. The axon of one cell terminates just dorsally to the cell body. Fusiform cells have the characteristic spiny, apical and smooth, basal dendrites. The basal dendrites are conspicuously oriented parallel to isofrequency laminae. Axons of the fusiform cells exit through the dorsal acoustic stria without branching. The two tuberculoventral association cells in the deep DCN have axons that terminate both in the deep DCN, within the same isofrequency lamina that contains the cell body, and in the ventral cochlear nucleus (VCN). Intracellular recordings from 11 of these cells show that they cannot be distinguished on the basis of their responses to intracellularly injected current. All cell types fired large action potentials that were followed by a fast and a slower undershoot, distinguishing them from cells of the VCN but not from one another. Most cells responded to shocks of the auditory nerve root with early EPSPs and later IPSPs. The latencies of EPSPs show that some were monosynaptic and others polysynaptic. That there was no systematic relationship between the latencies of EPSPs and the cell types from which they were recorded shows that shocks to the nerve root may have activated more than just the large, myelinated, auditory nerve fibers.     

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.     

Formation of the avian nucleus magnocellularis from the auditory anlage

In the avian auditory system, the neural network for computing the localization of sound in space begins with bilateral innervation of nucleus laminaris (NL) by nucleus magnocellularis (NM) neurons. We used antibodies against the neural specific markers Hu C/D, neurofilament, and SV2 together with retrograde fluorescent dextran labeling from the contralateral hindbrain to identify NM neurons within the anlage and follow their development. NM neurons could be identified by retrograde labeling as early as embryonic day (E) 6. While the auditory anlage organized itself into NM and NL in a rostral-to-caudal fashion between E6 and E8, labeled NM neurons were visible throughout the extent of the anlage at E6. By observing the pattern of neuronal rearrangements together with the pattern of contralaterally projecting NM fibers, we could identify NL in the ventral anlage. Ipsilateral NM fibers contacted the developing NL at E8, well after NM collaterals had projected contralaterally. Furthermore, the formation of ipsilateral connections between NM and NL neurons appeared to coincide with the arrival of VIIIth nerve fibers in NM. By E10, immunoreactivity for SV2 was heavily concentrated in the dorsal and ventral neuropils of NL. Thus, extensive pathfinding and morphological rearrangement of central auditory nuclei occurs well before the arrival of cochlear afferents. Our results suggest that NM neurons may play a central role in formation of tonotopic connections in the auditory system.     

Trauma-specific insults to the cochlear nucleus in the rat

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA‐type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN. © 2012 Wiley Periodicals, Inc.     

Afferent and efferent innervation patterns of the cochlear nucleus (dorsal medullary nucleus) of the leopard frog

The afferent and efferent innervation patterns of the frog dorsal medullary nucleus (DMN; anuran homolog of the cochlear nucleus) were examined by studying the anterograde and retrograde transport patterns of horseradish peroxidase injected focally into the nucleus. It was found that this structure projected bilaterally to the superior olivary nuclei (SON) and dorsal midbrain tegmental nuclei, and contralaterally to the opposite DMN, the lateral lemniscus nucleus (LLN) and the torus semicircularis (TS). The termination sites in the TS were restricted to the laminar and principal nuclei. The DMN in turn received projections from these structures with the exception of the TS and dorsal tegmental nuclei. The projection to the ipsilateral LLN and TS was not pronounced. In addition to the above findings, the ascending projection to the DMN, SON and TS, as well as the centrifugal projection from the SON, were found to be organized tonotopically.     

Late appearance and deprivation-sensitive growth of permanent dendrites in the avian cochlear nucleus (Nuc. magnocellularis)

The second-order auditory neurons in the avian nucleus magnocellularis (NM) do not begin to grow permanent dendrites until about embryonic day 17 (E17), a few days before hatching. Since the auditory periphery and brain-stem auditory nuclei are functional by E14 at the latest, the late appearance and growth of permanent dendrites in NM provides an unusual opportunity to examine the role of sensory experience in the very early stages of dendritic growth. We studied the development of NM dendrites in normal chickens and in animals with sustained monaural acoustic deprivation. In Golgi-Hortega preparations at E17 and posthatching days 4 (P4), 10 (P10), and 60 (P60), the proportion of stained NM neurons with a dendritic process (“dendritic neurons”) and the length of these dendrites were measured. In normal animals the mean proportion of dendritic neurons rose from about 14% at E17 to 40% at P4 and thereafter. The mean length of NM dendrites in normal animals, however, grew significantly until P10, rising from about 14 μm at E17 to 48 μm by P4, and about 100 μm at P10 and P60. A 40-dB monaural conductive hearing loss maintained with plastic earplugs from E18 on produced substantial retardation of dendritic growth after P4; at P10 the difference in length between deprived and nondeprived dendrites was 32% and at P60 was 38%. The proportion of dendritic neurons in the deprived NM and the mean diameter of the deprived dendrites were not affected by deprivation. Deprived dendrites in experimental animals were also significantly shorter than those in normal control animals. The length of nondeprived dendrites in experimental animals did not differ from that of controls, arguing against any compensatory hypertrophy. The functions of NM dendrites in the central processing of auditory information are as yet unknown. The facts that these dendrites (1) undergo their most rapid growth during the period of the animal's first exposure to airborne sound and (2) are markedly stunted by a nondeafferenting moderately severe acoustic deprivation suggest that acoustic experience has a strong facilitative function in the posthatching development of the cochlear nucleus. These results also suggest that afferent synaptic stimulation can affect the subsequent elongation, but not the initial outgrowth, of dendrites.     

In vivo optical imaging of tone-evoked activity in the dorsal cochlear nucleus with a voltage sensitive dye

We investigated the use of optical imaging for observing the spatial patterns of neural activation in the dorsal cochlear nucleus (DCN) of hamsters during tonal stimulation. The patterns of activation were studied in the DCN, in vivo, following application of a voltage sensitive dye, Di-2-ANEPEQ, to the DCN surface. Beginning 60-90 min following dye application, tones were presented to the ipsilateral ear. Electrophysiological recordings after dye application revealed no significant toxicity of Di-2-ANEPEQ that affected the frequency-tuning properties of DCN neurons. We examined areas of activation in response to each of a series of test stimuli consisting of pure tones ranging in frequency from 2 to 20 kHz. For each stimulus condition, images were collected over a stimulus interval of 400 msec and averaged over 32 stimulus repetitions. These images revealed areas of activation with definable epicenters. The epicenters shifted from lateral to more medial locations on the DCN surface with increases in stimulus frequency. Comparison with electrophysiological data indicated a close parallel between the tonotopic gradient defined by optical imaging and that defined by the distribution of characteristic frequencies. The principal temporal and spatial features of these optical responses are described.     

Functional organization of ascending and descending connections of the cochlear nucleus of horseshoe bats.

The ascending projections of the cochlear nucleus (CN) and the sources of descending inputs to the CN were investigated in horseshoe bats (Rhinolophus rouxi) by tracing the anterograde and retrograde transport of horseradish peroxidase (HRP or WGA-HRP) injected into the CN. The tracer was iontophoretically deposited into physiologically characterized regions of the cochlear nucleus (Feng and Vater, '85). We report the course and termination of pathways arising from the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nucleus. The projection fields within the auditory brainstem centers (superior olivary complex [SOC]; lateral lemniscus complex [LLC]; and inferior colliculus [IC]) and their tonotopic organization according to the frequency representations at the injection sites are described. While the projection pattern is generally in accordance with other mammals, several species-characteristic features are noted: i) the lateral superior olive (LSO) receives tonotopically organized input from both the AVCN and PVCN; ii) the CN-projections to medial nuclear groups of the SOC located between the LSO and the medial nucleus of the trapezoid body do not support previously suggested homologies; iii) the ventral nucleus of the LLC can be subdivided into two divisions with distinct input patterns from the AVCN and PVCN, respectively.     

GABA neurons in the superficial layers of the rat dorsal cochlear nucleus: light and electron microscopic immunocytochemistry

This article is an application of light and electron microscopic immunocytochemistry to the study of the neuronal circuit of the superficial layers in the rat dorsal cochlear nucleus (DCN). An antiserum against the intrinsic marker glutamate decarboxylase (GAD) is used to identify and map axon terminals and neurons that use gamma aminobutyric acid (GABA) as a neurotransmitter. It is demonstrated that layers 1 and 2 of the DCN contain a very high density of GABAergic boutons, matched only by the granule cell domains of the ventral cochlear nucleus, especially the superficial granule cell domain. These two layers also contain much higher concentrations of GABAergic cell bodies than all other magnocellular regions of the cochlear nuclear complex. Cartwheel and stellate neurons, and probably also Golgi cells, previously characterized in Golgi and electron microscopic investigations, appear immunostained and, therefore, are presumably inhibitory. The synaptic relations between parallel fibers, the axons of granule cells, and cartwheel and stellate neurons are confirmed. The present study also supports the conclusion that stellate cells are coupled to one another by gap junctions. Also scattered in layer 1 are large, GABAergic neurons that occur with irregular frequency and presumably represent displaced Purkinje cells, previously identified with a Purkinje-cell-specific marker. Granule neurons and pyramidal neurons remain unstained, even after topical injection of colchicine, which enhances immunostaining of the other glutamate-decarboxylase-positive cells, and therefore must use transmitters different from GABA. The possible analogies between the spiny cartwheel and the aspiny stellate cells of the DCN and the cerebellar Purkinje and stellate/basket cells are discussed in the light of data from Golgi, electron microscopy, and transmitter imunocytochemistry.     

Changes in the tonotopic map of the dorsal cochlear nucleus in hamsters with hair cell loss and radial nerve bundle degeneration

Hamsters were exposed to an intense tone (10 kHz) at levels and durations sufficient to cause hair cell loss and radial nerve bundle degeneration. A previous study reported changes in the tonotopic map of the dorsal cochlear nucleus (DCN) in hamsters with tone-induced stereocilia loss. Such changes appear similar to those observed by others in the auditory nerve following acoustic trauma, and suggest that the map alterations have a peripheral origin. However, the potential for tonotopic map reorganization after more severe lesions involving cellular degeneration in the cochlea has not yet been determined. The purpose of the present study was to determine how the tonotopic map of the DCN appears in animals with severe cochlear injury involving hair cell loss and radial nerve bundle degeneration. Neural population thresholds and tonotopic organization were mapped over the surface of the DCN in normal unexposed animals and those showing tone-induced lesions. The results indicate that cochlear lesions characterized mainly by radial bundle degeneration in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization (i.e., plasticity). However, these expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning following tone-induced loss of anatomical input to the central auditory pathway are similar to those observed in our previous study and by others in the auditory nerve following less severe acoustic trauma, and thus would seem to have a peripheral origin. Thus, changes in the DCN tonotopic map can be explained by peripheral modifications and do not seem to involve plastic changes (i.e., reorganization).     

Chronic neurotrophin delivery promotes ectopic neurite growth from the spiral ganglion of deafened cochleae without compromising the spatial selectivity of cochlear implants

Cochlear implants restore hearing cues in the severe–profoundly deaf by electrically stimulating spiral ganglion neurons (SGNs). However, SGNs degenerate following loss of cochlear hair cells, due at least in part to a reduction in the endogenous neurotrophin (NT) supply, normally provided by hair cells and supporting cells of the organ of Corti. Delivering exogenous NTs to the cochlea can rescue SGNs from degeneration and can also promote the ectopic growth of SGN neurites. This resprouting may disrupt the cochleotopic organization upon which cochlear implants rely to impart pitch cues. Using retrograde labeling and confocal imaging of SGNs, we determined the extent of neurite growth following 28 days of exogenous NT treatment in deafened guinea pigs with and without chronic electrical stimulation (ES). On completion of this treatment, we measured the spread of neural activation to intracochlear ES by recording neural responses across the cochleotopically organized inferior colliculus using multichannel recording techniques. Although NT treatment significantly increased both the length and the lateral extent of growth of neurites along the cochlea compared with deafened controls, these anatomical changes did not affect the spread of neural activation when examined immediately after 28 days of NT treatment. NT treatment did, however, result in lower excitation thresholds compared with deafened controls. These data support the application of NTs for improved clinical outcomes for cochlear implant patients. J. Comp. Neurol. 521:2818–2832, 2013. © 2013 Wiley Periodicals, Inc.     

Developmental expression of a voltage-dependent potassium channel (Kv3.1) in auditory neurons without cochlear input.

Kv3.1, a voltage-dependent potassium channel, has two forms, -a and -b, which differ in expression during development and at the onset of function in the auditory system. To determine whether cochlear nerve input could affect the expression of these two forms, cultures of the developing cochlear nucleus were explanted in the absence of the cochlear nerve at the beginning of cell migration (Hamburger-Hamilton stage 28-30), while neuroblasts continued to migrate onto the culture substrate. After 8, 15, and 22 days in vitro (three survival groups), cultures were immunostained with antibodies recognizing either both forms of Kv3.1 or only the -b form. Only young and newly migrated nerve cells were sampled. In the three survival groups, all nerve cells expressed Kv3.1, among which only 50% or less expressed the -b form. Some of the more differentiated multipolar cells expressed the -b form, but most were labeled with the antibody that recognizes both forms. Thus, in the absence of peripheral input, both forms of Kv3.1 appear at stages very early in development, although not all cells necessarily coexpress both forms. These results agree with other observations in the chick embryo in situ. They are consistent with previous work implicating Kv3.1 in cell migration during early development.