Degeneration in the ventral cochlear nucleus after severe noise damage in mice.

To study the mechanisms of noise-induced hearing loss and the phantom noise, or tinnitus, often associated with it, we used a mouse model of noise damage designed for reproducible and quantitative structural analyses. We selected the posteroventral cochlear nucleus, which has shown considerable plasticity in past studies, and correlated its changes with the distribution of neurotrophin 3 (NT3). We used volume change, optical density analysis, and microscopic cluster analysis to measure the degeneration after noise exposure. There was a fluctuation pattern in the reorganization of nerve terminals. The data suggest that the source and size of the nerve terminals affect their capacity for regeneration. We hypothesize that the deafferentation of ventral cochlear nucleus is the structural basis of noise-induced tinnitus. In addition, the immunofluorescent data show a possible connection between NT3 and astrocytes. There appears to be a compensatory process in the supporting glial cells during this degeneration. Glia may play a role in the mechanisms of noise-induced hearing loss.

Postnatal development of NT3 and TrkC in mouse ventral cochlear nucleus.

In the developing nervous system, neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF) have been shown to interact with each other and with different parts of a neuron or glia and over considerable distances in time and space. The auditory system provides a useful model for analyzing these events, insofar as it is subdivided into well-defined groups of specific neuronal types that are readily related to each other at each stage of development. Previous work in our laboratory suggested that NT3 and its receptor TrkC in the mouse cochlear nucleus (CN) may be involved in directing neuronal migration and initial targeting of inputs from cochlear nerve axons in the embryo. NT3 is hard to detect soon after birth, but TrkC lingers longer. Here we found NT3 and TrkC around P8 and the peak around P30. Prominent in ventral CN, associated with globular bushy cells and stellate cells, they were localized to different subcellular sites. The TrkC immunostain was cytoplasmic, and that of NT3 was axonal and perisomatic. TrkC may be made by CN neurons, whereas NT3 has a cochlear origin. The temporal pattern of their development and the likelihood of activity-dependent release of NT3 from cochlear axons suggest that it may not be critical in early synaptogenesis; it may provide long-term trophic effects, including stabilization of synapses once established. Activity-related regulation could coordinate the supply of NT3 with inner ear activity. This may require interaction with other neurotrophins, such as BDNF.

Inactivation of fibroblast growth factor receptor signaling in myelinating glial cells results in significant loss of adult spiral ganglion neurons accompanied by age-related hearing impairment.

Hearing loss has been attributed to many factors, including degeneration of sensory neurons in the auditory pathway and demyelination along the cochlear nerve. Fibroblast growth factors (FGFs), which signal through four receptors (Fgfrs), are produced by auditory neurons and play a key role in embryonic development of the cochlea and in neuroprotection against sound-induced injury. However, the role of FGF signaling in the maintenance of normal auditory function in adult and aging mice remains to be elucidated. Furthermore, the contribution of glial cells, which myelinate the cochlear nerves, is poorly understood. To address these questions, we generated transgenic mice in which Fgfr1 and Fgfr2 were specifically inactivated in Schwann cells and oligodendrocytes but not in neurons. Adult mutant mice exhibited late onset of hearing impairment, which progressed markedly with age. The hearing impairment was accompanied by significant loss of myelinated spiral ganglion neurons. The pathology extended into the cochlear nucleus, without apparent loss of myelin or of the deletion-bearing glial cells themselves. This suggests that perturbation of FGF receptor-mediated glial function leads to the attenuation of glial support of neurons, leading to their loss and impairment of auditory functions. Thus, FGF/FGF receptor signaling provides a potentially novel mechanism of maintaining reciprocal interactions between neurons and glia in adult and aging animals. Dysfunction of glial cells and FGF receptor signaling may therefore be implicated in neurodegenerative hearing loss associated with normal aging.

Synaptic relationships of Golgi type II cells in the medial geniculate body of the cat.

A combined analysis with the Golgi and silver-degeneration methods and electron microscopy in the ventral nucleus of the medial geniculate body has confirmed that the Golgi type II neuron forms dendro-dendritic synapses with the principal neuron in terminal aggregates called synaptic nests. Both types of neurons receive synaptic contacts from the afferent axons that ascend from the posterior colliculus and from those that descend from the auditory cortex. Only the principal neuron projects to the auditory cortex. The Golgi type II cells that receive endings from afferent axons send presynaptic processes to principal cells that are also contacted by the very same afferent axons. The axons of Golgi type II cells project to synaptic nests other than those supplied by the dendrites of the parent cell and link the Golgi type II cells with each other. On the surface of the Golgi type II cell there is a segregation of the different types of synaptic endings and a consistent sequence in their synaptic relationships. The endings of colliculogeniculate and Golgi type II axons predominate on the distal dendrites in the synaptic nests. Corticogeniculate endings congregate more on the soma and proximal dendrites. In the synaptic nests the Golgi type II dendrites are presynaptic to the principal cell dendrites, whereas both kinds of dendrites are postsynaptic to the very same axons, which project either from the posterior colliculus or from Golgi II cells...

Synaptic organization of globular bushy cells in the ventral cochlear nucleus of the cat: a quantitative study.

The synaptic organization of globular bushy cells of the anteroventral cochlear nucleus was quantitatively analyzed in order to understand better their functional attributes. A method was devised to estimate the concentrations and relative proportions of synapses on the entire postsynaptic surface of Golgi-impregnated neurons, by sampling with limited series of sections for electron microscopy. This provided a characteristic synaptic profile which was homogeneous for the population measured. The total concentration of synaptic endings decreases with distance from the soma. The cochlear, presumably glutamatergic and excitatory, endings with large spherical vesicles (LS) account for most of this decrease. Of the noncochlear inputs, the putative glycinergic endings with flattened vesicles (FL) decrease slightly, and the presumed GABAergic terminals with pleomorphic vesicles (PL) maintain a relatively constant concentration, while endings with small spherical vesicles (SS) increase on the distal dendrites. LS endings have the largest proportion of synapses near the soma, while FL synapses maintain a constant proportion in all cell regions, and PL and SS proportions increase on higher-order dendrites. Excitatory and inhibitory synapses have significant inputs to the axon hillock and initial segment, as well as to the distal dendrites, where dual synapses may provide a way to sample the activity of surrounding neurons. These features must be considered in explanations of physiological properties, such as the synaptic security, level of spontaneous activity, and well-timed, rapid onset responses, as well as their potential for normalizing and synchronizing an important inhibitory pathway involved in binaural signal processing. Synaptic profile analysis should be useful for experimental studies and for developing realistic computational models.

Relations between auditory nerve endings and cell types in the cat's anteroventral cochlear nucleus seen with the Golgi method and Nomarski optics.

Rapid Golgi impregnations of the ascending branches of the auditory nerve fibers and of the types of neurons in the anteroventral cochlear nucleus (AVCN) were studied. Entire ascending branches could be observed, some of these branches project to each subdivision, others do not. There are two main typesof large neurons: the bushy and stellate cells. Criteria were established for identifying unimpregnated bushy and stellate perikarya by means of Nomarski optics, and these criteria were checked by Momarski observations on neurons which had either impregnated dendrites and unimpregnated cell bodies or impregnated portions of perikarya. In this way, the relations of unimpregnated cell bodies to auditory nerve endings were observed. Furthermore, with Nomarski optics, the cytoarchitectonic subdivisions of AVCN could be determined. Differences in the end-bulbs and collateral endings formed by the auditory nerve fibers were distinguished in three of the cytoarchitectonic subdivisions of the AVCN. End-bulbs in the anterior division were much larger than those in the dorsal and ventral parts of the posterior division. The large end-bulbs of Held in the anterior division of the AVCN were consistently associated with the perikarya of bushy cells and not with those of stellate cells. The large end-bulbs are not observed in the posterior division. Thus, bushy cells in the posterior division, although morphologically similar to those in the anterior division, must have a different synaptic organization. This difference may correspond to electrophysiological distinctions in the time-patterns of response recorded in these regions following acoustic stimulation.

Fine structure of the cell clusters in the cochlear nerve root: stellate, granule, and mitt cells offer insights into the synaptic organization of local circuit neurons.

The small cell shell of the cochlear nucleus contains a complex integrative machinery which can be used to study the roles of interneurons in sensory processing. The cell clusters in the cochlear nerve root of the chinchilla provide the simplest example of this structure. Reported here are the neuronal architecture and synaptic organization of the three principal cell types and the three distinctive neuropil structures that could be characterized with the Nissl and Golgi methods and electron microscopy. Granule cells were characterized by several dendrites with claw-like terminals that received synaptic contacts from multiple excitatory mossy fiber rosettes. Given their relatively large number and their prolific parallel fiber synapses, the granule cells provide a suitable substrate for a tangential spread of excitatory activity, which could build to considerable proportions. The mitt cells had a thickened, single dendrite, its terminal branches arranged in a shape reminiscent of a baseball catcher's mitt. The dendritic mitt enclosed an enormous, convoluted mossy fiber rosette forming many excitatory synapses on just one cell. This could provide for a discrete, comparatively fast input-output relay of signals. Small stellate cells had longer, radiating dendrites that engaged the synaptic nests. These nests were strung in long strands, containing heterogeneous synapses from putative excitatory and inhibitory inputs. Given the prevalence of the synaptic nests, the small stellate cells appear to have the greatest integrative capacity. They provide the main output of the synaptic nests.

Migration of neuroblasts by perikaryal translocation: role of cellular elongation and axonal outgrowth in the acoustic nuclei of the chick embryo medulla.

The neuroblasts forming nucleus magnocellularis, the avian homologue of the mammalian ventral cochlear nucleus, migrate by growth and elongation of their leading processes and by perikaryal translocation through these processes from the matrix zone of the rhombic lip to the acoustico-vestibular anlage. Golgi methods were used on staged chick embryos to reconstruct the morphogenetic phases of migration and early differentiation in situ. Fluorescence labeling of the living cells in vitro elucidated the role of axonal growth in the migratory process. In situ, branching cochlear nerve fibers, tipped with growth cones, enter the acoustico-vestibular anlage at E4.5-5.5 before migration of the magnocellularis neuroblasts at E.5.5-6.5. The premigratory neuroblasts in the matrix zone of the rhombic lip resemble primitive epithelial cells, which extend branched, curving processes into a characteristic formation, the rhombic whorl. The leading process of the migrating magnocellularis neuroblasts gives rise to a bifurcating axon at the interface between the matrix and mantle zones. The lateral branch becomes the recurrent ipsilateral collateral; the medial branch crosses the midline, heading toward the contralateral target site in the region of the presumptive nucleus laminaris. The cell bodies of the migratory neuroblasts appear in intermediate locations along the migration route as they translocate radially through their leading processes past the axonal bifurcation and then tangentially and obliquely into the mantle zone. Neuroblasts destined for nucleus laminaris migrate coincidentally with magnocellularis neuroblasts. Nucleus angularis neuroblasts migrate later in development, after E6.5. In vitro, injections of a nontoxic fluorescent dye (diI) were made into explants of the medulla in the region of the contralateral target area at the time of neuroblast migration. DiI retrogradely labeled the cell bodies of premigratory magnocellularis neuroblasts in the matrix zone and of migratory neuroblasts in the mantle zone through their medial, crossing axonal branches. The morphology of the living neuroblasts in the explants resembled that in the Golgi impregnations at the corresponding stages of migration. Anterograde axonal transport also occurred. These results demonstrate migration by perikaryal translocation and early axon extension of a specific group of neuroblasts in the central nervous system. The morphology of the migrating neuroblasts is such that a simple radial arrangement of cellular guides, glial or otherwise, would not account for their configurations. The available evidence supports the proposition that cellular elongation and perikaryal translocation constitute the general mode of neuronal migration in the central nervous system. The early extension of axons into their target sites may play a critical role in migration and early development of specific types of neurons.

A study of cochlear innervation patterns in cats and rats with the Golgi method and Nomarkski Optics.

Cochlear innervation patterns were studied in infant cats and rats with the rapid Golgi method. Examination of thick serial sections and surface preparations with the differential interference contrast microscope (Nomarski optics) allowed direct visualization of individually impregnated spiral ganglion cells, complete with their peripheral processes and endings in the organ of Corti. Individually impregnated efferent fibers could be recognized as heavily varicose axons that project radially to endings beneath inner and outer hair cells after taking a tangential course in the intraganglionic spiral bundle. It was often possible to visualize unimpregnated hair cells in contact with the impregnated endings of both types of fibers. There are at least two types of spiral ganglion cells in the cochlea of the infant cat and rat. One type innervates only inner hair cells by means of radial fibers. These ganglion cells constitute the overwhelming majority of ganglion cells impregnated in our preparations, and each cell typically innervates two inner hair cells. Hence, these ganglion cells establish nearly "point-to-point" connections between the auditory nerve and the organ of Corti. The other type of ganglion cell innervates outer hair cells by means of long spiral fibers; each cell typically innervates many outer hair cells through the numerous angular enlargements and short end branches of its spiral fiber. In addition, a few of these spiral fibers also send branches to inner hair cells by means of short collaterals; it remains to be seen if such fibers also occur in mature cochleas. Efferent fibers have been traced to inner and outer hair cell regions. The simplest pattern is formed by fine beaded axons with only a few branches ending mainly beneath inner hair cells. More complex patterns are formed by larger axons with many branches ending beneath inner or outer hair cells. Many efferent fibers send branches to both inner and outer hair cells. Electrophysiological studies so far have not demonstrated different populations of units that clearly correspond to the spiral and radial fibers. Therefore, the physilogical differences between inner and outer hair cell innervation remain undefined.

The neuronal architecture of the dorsal division of the medial geniculate body of the cat. A study with the rapid Golgi method.

The neurons in the nuclei of the dorsal division of the medial geniculate body were studied with the rapid Golgi method in kittens and young adult cats. The dorsal nuclei contain two principal cell types: a large stellate neuron with radiate dendrites and a bushy neuron with tufted dendrites, each with extensive dendritic fields. Two sizes of cells with locally arborizing axons (local circuit neurons) were found. The small and commonly observed one is stellate in shape, has a limited dendritic domain, and an axon with multiple, often profuse collaterals ending in the vicinity of the cell. A second, and much less common variety (large local circuit neuron) is somewhat larger and has fewer axon collaterals. Subtle, but distinct variations in these cell types distinguish the deep and superficial dorsal nuclei and also the anterior tier of nuclei (deep dorsal and superficial). These functional differences may correlate with the relative morphological homogeneity of the ventral nucleus compared to the extremely heterogeneous medial division. The dorsal division should be regarded as part of the pulvinar-lateralis posterior complex both structurally and functionally. In the suprageniculate nucleus, the principal neurons are stellate cells with large perikarya and numerous and extensive dendrites covered with appendages. The large axon is devoid of collaterals. A small local circuit cell with several axon collaterals, and sparse, restricted dendrites has also been observed. In the adjacent posterior limitans nucleus, the principal neuron has a medium-sized, piriform or somewhat elongated perikaryon, a few very long radiating dendrites, which may span the depth of the nucleus, and a long, poorly branched axon. Small neurons are also seen here. A comparison of the structure, connections, and function of the medial geniculate body suggests that the dorsal division is predominantly, but probably not exclusively auditory, while the ventral nucleus is entirely auditory and relatively homogeneous, and the medial division, polymodal and heterogeneous with respect to input.

The neuronal architecture of the inferior colliculus in the cat: defining the functional anatomy of the auditory midbrain.

This study defines anatomical subdivisions in Golgi-impregnated material from the inferior colliculus of the cat. The findings demonstrate that the inferior colliculus consists of a mosaic of morphologically distinct parts of neuropil. Each part is also characterized by a unique set of neuronal types. Each part of the inferior colliculus can be defined as tectal or tegmental on the basis of the fundamental pattern of dendritic branching. The main subdivisions of the auditory tectum are the central nucleus, the cortex, and the paracentral nuclei. The central nucleus is distinguished by its laminated neuropil composed of neurons with disc-shaped dendritic fields oriented in parallel arrays with the lemniscal axons. In contrast, the cortex is identified by its broad layers of loosely woven neuropil, which are orthogonal to those in the central nucleus and lack neurons with disc-shaped dendritic fields. The paracentral nuclei, so called because of their scattered arrangement around the central nucleus, are the commissural, dorsomedial, rostral pole, lateral, and ventrolateral nuclei. The main subdivisions of the auditory tegmentum are the pericollicular areas, the nucleus of the brachium of the inferior colliculus, and the sagulum. The pericollicular areas are intercollicular or subcollicular and separate the tectal division from the superior colliculus, central gray, and remaining portions of the tegmentum. The afferent projections to each tectal and tegmental subdivision, as observed in silver-degeneration experiments, distinguish the parcellations based on the Golgi findings. Subdivisions containing tectal cell types receive afferents predominantly from the auditory pathways, in contrast to subdivisions with tegmental cell types, which receive inputs from a wide variety of sources. This suggests a correlation between neuronal types and the nature of their inputs. This analysis of the subdivisions of the inferior colliculus differs from previous studies, especially those relying on Nissl stains. It is likely that subdivisions distinguished by the pattern of the neuropil differ functionally, since the structural components identified in the Golgi-impregnated material are essential parts of the synaptic organization of the auditory midbrain. Future physiological studies should benefit from approaches in which the cell types serve as the focus for the analysis.

The central nucleus of the inferior colliculus in the cat.

The central nucleus of the inferior colliculus in the cat is distinguished by its unique neuropil. In Golgi-impregnated material, it is composed primarily of neurons with disc-shaped dendritic fields arranged into parallel arrays, or laminae, complemented by the laminar afferent axons from the lateral lemniscus. Large, medium-large, medium, and small varieties of disc-shaped cells are distinguished on the basis of the size of the dendritic field and cell body size, dendritic diameter, and dendritic appendages. A second major class of neurons in the central nucleus are the stellate cells with dichotomously branched, spherical-shaped dendritic trees. Simple, complex, and small stellate cells can be distinguished by their size and by the complexity of the dendritic and axonal branching. Laminar afferent axons are recognized by the nests of collateral side branches and the grapelike clusters of terminal boutons--thick, thin, and intermediate-sized varieties are apparent. Other axon types include local collaterals of central nucleus neurons, some of which are distinguished by their frequent and complex collaterals. In the central nucleus, the configuration of the fibrodendritic laminae, the presence of subdivisions, and the banding of afferent axons suggest levels of organization which are superimposed on the synaptic arrangements of the individual cell and axon types. The laminar pattern, as studied in serial Golgi-impregnated sections, differs from previous reports. The central nucleus contains subdivisions which can be distinguished by their laminar pattern, different proportions of cell types, and the packing density of the cell bodies and axonal plexus. The patterns of degeneration observed in Nauta-stained material after lesions of caudal auditory pathways show that thick and fine afferent fibers form dense bands of degeneration separated by sparse, fine-fiber degeneration. The bands are thicker than individual laminae but smaller than the subdivisions. The intrinsic organization of the neurons and axons, combined with the laminar organization, subdivisions, and banding patterns, each may contribute different aspects to the processing of auditory information in the central nucleus.

Axons of the dorsal division of the medial geniculate body of the cat: a study with the rapid Golgi method.

The arrangement of eight groups of axons afferent to the nuclei of the dorsal division of the medial geniculate body is described in rapid Golgi impregnations from young cats. Three kinds of axons travel predominantly in the brachium of the inferior colliculus and enter the medial geniculate body ventromedially: group I, thin axons resembling ivy tendrils ending along dendrites; group II, thicker axons with a sinuous course and few branches; group IV, coarse thick axons with grumous collaterals and massive peridendritic terminals near principal cells and interneurons. Three kinds of axons enter from the parabrachial region and pass laterally: group III, very thin axons with many collaterals forming dense terminal nests; group V, runcinate axons with sparse, thin collaterals; group VI, either medium-sized (group VIa) or thin (group VIb) smooth axons, perhaps corticofugal, and ending near principal neuron dendrites; group VII, thick axons, entering from the auditory radiation, with large, grapelike terminal arbors; and group VIII, thin and forming peridendritic festoons on principal cells after entering from the brachium of the superior colliculus. There appears to be some, though not complete, segregation of axons in the dorsal division nuclei. Thus axons of groups I, III, IV, and VI are found in each nucleus, although group VI axons are conspicuous in the superficial dorsal nucleus, and group IV endings are much more elaborate in the dorsal and deep dorsal nuclei than in the superficial dorsal nucleus. Each axon type has a specific pattern of terminal branches, which contributes to the texture of the neuropil in each nucleus. Golgi type II axons accentuate these textural differences. Thus each nucleus has a specific pattern of neuropil by virtue of the relative proportions of the different groups of axons ending there and the density and architecture of the axonal plexus. For example, both the dorsal nucleus and the deep dorsal nucleus receive the same groups of afferent axons, but the axonal plexus is more diffusely and evenly distributed in the dorsal nucleus, whereas the neuropil of the deep dorsal nucleus is highlighted by aggregates of grumous endings, more irregularities in the distribution of the axonal plexus, and many more fibers of passage. The extrinsic axons in the dorsal division come from the inferior and superior colliculi, the lateral tegmental system of the midbrain, and the cerebral cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

A physiological and structural study of neuron types in the cochlear nucleus. II. Neuron types and their structural correlation with response properties.

The present study examined the morphological cell types of neurons labeled with intracellular horseradish peroxidase injections, many of them following electrophysiological recordings in the cochlear nucleus of gerbils and chinchillas. Most of the subdivisions and neuronal types previously described in the cat were identified in the present material, including spherical and globular bushy cells, stellate, bushy multipolar, elongate, octopus, and giant cells in the ventral cochlear nucleus, and a cartwheel cell in the dorsal cochlear nucleus. In many cases these structurally distinct neurons were correlated with their characteristic responses to stimulation by sound or intracellular injection of depolarizing current. The dendritic terminals of the elongate, antenniform, and clavate cells of the posteroventral cochlear nucleus link each of these cell types with neighboring structures in distinct patterns, which may provide a basis for differences in synaptic organization. These cell types differ from each other and from the stellate cells of the anteroventral cochlear nucleus. Despite their heterogeneous morphology, most of these neurons had a regular discharge in response to stimulation (choppers). Irregularly firing neurons (primary-like) had very different structures, e.g., the spherical and globular bushy cells and the bushy multipolar neuron. They, too, represent a heterogeneous population. An onset neuron was identified as an octopus cell. This paper compares the morphological observations with the electrophysiological properties of different cell types reported in a companion paper (Feng et al. [1994] J. Comp. Neurol.). Together, these findings imply that response properties may be partially independent of neuronal structure. Morphologically distinct neurons can generate similar temporal patterns in response to simple acoustic stimuli. Nevertheless, the synaptic organization of these different neuron types, including their connections, would be expected to affect or alter the cells' responses to appropriate stimuli. The possibility is raised that membrane properties and synaptic organization complement and interact with each other.

A cytoarchitectonic atlas of the medial geniculate body of the opossum, Didelphys virginiana, with a comment on the posterior intralaminar nuclei of the thalamus.

The organization of the medial geniculate body and adjacent posterior thalamus of the Virginia opossum was studied in Nissl-, Golgi-, reduced silver, and myelin-stained preparations. Our chief goals were to define the cytoarchitectonic subdivisions and boundaries in Nissl preparations and to reconcile these with those observed with the Golgi method and in experimental material, to present these results in an atlas of Nissl-stained sections, and to compare the chief nuclear groups in the opossum and the cat medial geniculate body. In the opossum, the ventral division consists chiefly of the ventral nucleus. The ventral nucleus is divided into two main parts: the pars lateralis and the pars ovoidea, the former being relatively smaller in the opossum. The ventral nucleus of both species contains large principal neurons with bushy, tufted dendrites and smaller Golgi type II cells. However, the opossum has far fewer Golgi type II cells, and the texture of the neuropil is correspondingly different, although the primary ascending input from the midbrain arises from the central nucleus of the inferior colliculus in both species. The dorsal division consists of the dorsal nuclei, including the suprageniculate nucleus and the caudal part of the lateral posterior nucleus, the marginal zone, and the posterior limitans nucleus. These nuclei are identified in both species, although they are much smaller in the opossum. The neurons consist of medium-size and small somata with a predominantly radiate mode of dendritic branching and a lower cell concentration than in the ventral division. In both species the afferent brain stem input comes from the inferior colliculus, the lateral tegmental area, the intercollicular tegmentum, and the superior colliculus. The medial division contains several types of cells, which are heterogeneous in form and size, most having radiating dendrites and a low cellular concentration. This division is especially smaller in the opossum, although comparable inputs arise from various auditory and non-auditory sources in the midbrain and spinal cord in both species. A large intralaminar complex of nuclei occurs in the opossum, which have a more extensive distribution than previously appreciated. They not only occupy the intramedullary laminae but form a shell around the medial geniculate nuclei and adjoining main sensory nuclei. The intralaminar complex includes the posterior limitans, posterior intralaminar, posterior, parafascicular, posterior parafascicular, central intralaminar, limitans, and central medial nuclei, and the marginal zone of the medial geniculate body.(ABSTRACT TRUNCATED AT 400 WORDS)

A physiological and structural study of neuron types in the cochlear nucleus. I. Intracellular responses to acoustic stimulation and current injection.

Neurons in the cochlear nucleus differ in their discharge patterns when stimulated by tones. They also differ in their responses to depolarizing current injection in vitro. We made intracellular recordings from neurons in the cochlear nucleus of gerbils and chinchillas. The responses to tones and to depolarizing current were compared for the same neurons. Three categories of response patterns to tones were observed: chopper, primary-like, and onset. Chopper neurons responded with regularly spaced action potentials to stimulation with tones and to injections of depolarizing current. Their response rate rose with increasing levels of current to a maximum, which was comparable to that evoked by suprathreshold tones. These observations suggest that the regularity and maximal firing rate of these neurons are determined by voltage-dependent membrane properties. Primary-like neurons responded with irregularly spaced action potentials to tones. Injection of depolarizing current into these neurons produced a single action potential at current onset, which could be followed by a few irregularly spaced action potentials. The response rate showed little relation to current level. These data suggest that the membrane characteristics of primary-like neurons are different from those of chopper neurons. Onset neurons produced action potentials only at the beginning of the stimulus for both tones and depolarizing current, even though there was a sustained depolarization throughout the duration of the tone. The findings suggest that cochlear nucleus neurons have different membrane properties and that these properties may play a critical role in a neuron's temporal response pattern to acoustic stimulation.

Glycine-immunoreactive projection of the cat lateral superior olive: possible role in midbrain ear dominance.

Neurons in the lateral superior olive are optimally excited by stimulation of the ipsilateral ear, as are those in the inferior colliculus by stimulation of the contralateral ear. This reversal of ear dominance may result, in part, from distinct crossed excitatory and uncrossed inhibitory pathways ascending from the lateral superior olive. To explore this possibility, immunoreactivity for two putative inhibitory neurotransmitters, glycine and GABA, was examined in projection neurons that retrogradely transported horseradish peroxidase from the cat inferior colliculus. The results suggest that the projection from the lateral superior olive can be segregated, immunocytochemically, into three components: 1) a crossed, glycine-negative (-) projection; 2) an uncrossed, glycine-positive (+) projection; and 3) an uncrossed, glycine(-) projection. Additional evidence suggests that the terminal fields of the two uncrossed projections may distribute differently within the inferior colliculus. Glycine(+) or glycine(-) projection neurons, crossed or uncrossed, do not differ in the size, shape, or location of their somata. However, most glycine(-) neurons are heavily encrusted with glycine(+) endings; glycine(+) neurons have 40-60% fewer of these endings. Glycine(-) neurons located in the lateral limb have fewer glycine (+) perisomatic endings than those in the medial limb. Few projection neurons are GABA(+), and GABA(+) perisomatic endings are rare in the lateral superior olive. Thus, there is a heavy uncrossed projection from the cat lateral superior olive to the inferior colliculus that may be glycinergic and inhibitory. Furthermore, there is a bilateral projection that is not glycinergic or GABAergic, which may be excitatory. The potential contribution of these pathways to contralateral ear dominance in the inferior colliculus is discussed.

The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: Golgi and Nissl methods.

This report characterizes the cells and fibers in one part of the cochlear nucleus, the posterior division of the anteroventral cochlear nucleus. This includes the region where the cochlear nerve root enters the brain and begins to form endings. Nissl stains reveal the somata of globular cells with dispersed Nissl substance and those of multipolar cells with coarse, clumped Nissl bodies. Both parts of the posterior division contain cells with each Nissl pattern, but in different relative numbers and locations. Golgi impregnations demonstrate two types of neurons: bushy cells, with short bush-like dendrites, and stellate and elongate cells, with long tapered dendrites. Several varieties of bushy cells, differing in the morphology of the cell body and in the size and extent of the dendritic field, can be distinguished. Comparison of the distributions of these cell types, as well as cellular morphology, suggest that the globular cells recognized in Nissl stains correspond to bushy neurons, while the multipolar cells correspond to stellate and elongate neurons. Golgi impregnations reveal large end-bulbs and smaller boutons from cochlear nerve fibers, as well as boutons from other, unidentified sources, ending in this region. The particular arrangements of the dendritic fields of the different cell types and the axonal endings associated with them indicate that these neurons must have different physiological properties, since they define different domains with respect to the cochlear and non-cochlear inputs.

The development of innervation patterns in the avian cochlea.

The sequence of developmental events leading to the innervation of the cochlea and the differentiation of its receptor cells has been studied in chick embryos with Golgi methods. We describe the morphogenesis of cochlear ganglion cell peripheral processes from their appearance in early embryos to the formation of their mature endings on hair cells in the basilar papilla (organ of Corti) of prehatching chicks. In the stage of peripheral fiber outgrowth, embryonic days 3-5, the fibers emerge from the ganglion cell bodies and grow, in a uniform fashion, toward the undifferentiated receptor epithelium of the otocyst. In the stage of the invasion of the otocyst by the peripheral fibers, embryonic days 6-7, some fibers enter the epithelium directly after reaching it, others enter after traveling some distance longitudinally beneath its basal lamina. The invading fibers appear to encounter resistance at the basal lamina, but, once within the epithelium, at embryonic days 8-9, they form a surfeit of branches in columnar zones oriented radially toward the surface. In early synaptogenesis (embryonic days 8-9) hair cells first become apparent. They differentiate from primitive epithelial cells. These cells withdraw their basal processes, which appear to accompany the growing fibers into the superficial epithelium. At embryonic days 11-13, the stage of mid-synaptogenesis, the fibers develop large, bulbous, preterminal and terminal swellings, which are located below the bases of the hair cells; the surplus branches atrophy or withdraw. Efferent axons are first seen in the epithelium at this time. In late synaptogenesis (embryonic days 14-17), the preterminal swellings disappear and the endings transform into mature foot-shapes at the bases of the hair cells. These morphological changes during the development of the peripheral endings are comparable to those of cochlear axons in nucleus magnocellularis (cochlear nucleus). During mid-synaptogenesis, when the ganglion cells develop swellings in the periphery, their central axons ramify extensively. Late in synaptogenesis, while the peripheral swellings disappear, there is a corresponding condensation of the central terminals to form the end-bulbs of Held. Thus, specific connections of the cochlear ganglion cells and their target cells in the ear and brain may result from two sequential developmental phases: (1) loosely organized and overabundant initial growth of branches from the fibers entering their target tissue; (2) reorganization of these fibers with the disappearance or resorption of the surplus branches during the transformation of their endings into mature synaptic arrangements.(ABSTRACT TRUNCATED AT 400 WORDS)