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Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal trigeminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1-C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correction for the effects of pinna orientation on sound-localization cues.

Acoustic Stimulation↗

Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localizations in the dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is a major brain center for integration of auditory information, and excitatory amino acid neurotransmission plays a central role in the processing of this information. In this study, the distribution of glutamate receptors was examined with preembedding immunocytochemistry, using 14 antibodies to ionotropic (GluR1, GluR2/3, GluR4, GluR5-7, GluR6/7, KA2, NR1, NR2A/B, delta 1/2) and metabotropic (mGluR1 alpha, mGluR2/3, mGluR5) glutamate receptor subtypes. Each of these antibodies produced a specific immunolabeling pattern, including a variety of postsynaptic, presynaptic, and glial localizations. Some antibodies showed widespread distribution patterns, notably the antibodies to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits, GluR2 and GluR3, and the N-methyl-D-aspartate (NMDA) receptor subunit, NR1. In contrast, antibodies to other glutamate receptor subunits produced more restricted distribution patterns, especially that to GluR1, which stained the outer neuropil of the DCN, cartwheel cells, and a small population of presumptive interneurons associated with the dorsal acoustic stria, but produced little or no staining in fusiform cells or deep DCN neurons. Staining of the postsynaptic density and membrane of the granule cell-parallel fiber/cartwheel cell spins synapse was most prevalent with delta 1/2 and mGluR1 alpha antibodies. A unique pattern of staining was found with mGluR2/3 antibody--with staining concentrated in Golgi cells and unipolar brush cells of the middle to deep DCN. Distribution of some glutamate receptors in the DCN shows similarities to that of the cerebellum, where delta 2 and mGluR1 alpha may modulate neurotransmission at parallel fiber synapses, while mGluR2 and/or mGluR3 may modulate mossy terminal function.

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Neuronal migration and differentiation in the development of the mouse dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) of mammals displays a cortical structure containing a number of cell types organized into distinct layers. In the present study, the migratory mode of large multipolar cells and granule cells as well as the morphological differentiation of the projection neurons were investigated in the development of the mouse DCN. The classification of the DCN neurons followed that of Ryugo and Willard. The mode of neuronal migration was examined by immunohistochemical bromodeoxyuridine labeling. Large multipolar neurons originated from the primary rhombic lip and small granule cells from the secondary rhombic lip. Large multipolar neurons migrated radially from the ventricular zone into the forming DCN. Granule cells were generated later than the large multipolar neurons and migrated via the subependymal and subpial routes. Large multipolar neurons and small granule cells were thus segregated early in the DCN development and intermixed later during perinatal maturation. Projection neurons retrogradely labeled by DiI application to the contralateral inferior colliculus showed neurite extension between the pial surface and the ventricular zone during migration in the DCN primordium. The retrogradely labeled projection neurons showed a well-differentiated morphology of the large multipolar neurons as early as the late embryonic stage. The arrangement of the radial glial processes coincided with that of the migratory projection neurons. The migratory immature neurons showed close apposition with the radial glial processes, suggesting that glial scaffolds are involved in the migration and settlement of the large multipolar neurons. Thus, it is suggested that the mode of migration and settlement of large multipolar neurons and granule cells in the developing DCN is highly similar to that of Purkinje and granule cell migration in the cerebellar development, based on the findings of this study and the structural similarity between the cerebellum and DCN.

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Pharmacological evidence of inhibitory and disinhibitory neuronal circuits in dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is rich in both glycine and GABA inhibitory neurotransmitter systems, and the response properties of its principal cells (pyramidal and giant cells) are strongly shaped by inhibitory inputs. For example, DCN principal cells often display highly nonmonotonic (so-called type IV) input-output functions in response to best-frequency (BF) tones. In this study, the inhibitory inputs onto the principal cell types and onto response types of known inhibitory interneurons were compared before and during iontophoretic application of the glycine- and GABA(A)-receptor antagonists, strychnine and bicuculline. Strychnine eliminates the central (on-BF) inhibitory area in type IV units, resulting in monotonic BF rate-level curves. Unexpectedly, bicuculline primarily enhances inhibition in principal-cell types; for example, type IV units are inhibited at lower sound levels in the presence of bicuculline. Principal cell types with weaker inhibitory inputs (type IV-T and type III units) are more strongly inhibited in the presence of bicuculline and usually are converted into type IV units. This enhancement of on-BF inhibition by bicuculline suggests a disinhibitory process involving GABA(A) action on a non-GABA(A)ergic inhibitory pathway. This latter pathway is probably glycinergic and involves type II units (deep-layer vertical cells) and/or complex-spiking units (superficial cartwheel cells) because both of these unit types are disinhibited by bicuculline. One intrinsic GABA(A) source could be the superficial stellate cells in DCN because bicuculline partly blocks the inhibition evoked by somatosensory-stimulated activation of the superficial granule-cell circuitry in DCN. Taken together, the results suggest that glycinergic circuits mediate directly the inhibition of DCN principal cells, but that GABA(A)ergic circuits modulate the strength of the inhibition.

Acoustic Stimulation↗

Functional synapse elimination in the developing avian cochlear nucleus with simultaneous reduction in cochlear nerve axon branching.

We studied the chick auditory system to determine whether there is a normal developmental reduction in the number of cochlear nerve axons innervating individual cochlear nucleus (nucleus magnocellularis, NM) neurons. We also examined the preterminal branching patterns of cochlear nerve axons during development. The number of cochlear nerve axons innervating individual NM neurons was estimated by counting the increments in the postsynaptic response as the intensity of cochlear nerve electrical stimulation was varied gradually; this number fell from a mean of 4.0 on embryonic day 13 (E13) to a mean of 2.2 on E17 and E18 and the 4th day after hatching. This highly reliable decline in functional convergence was accompanied by a decrease in the number of preterminal branches of cochlear nerve fibers innervating the NM. On E13 and E14, most axons stained by iontophoretic injections of horseradish peroxidase showed two distinct preterminal branches in the NM. By E17 and E18 and thereafter, cochlear nerve axons were unbranched and terminated with a characteristic single large calycine ending in the NM. There are about twice as many cochlear nerve axons as neurons in the NM and the number of fibers in the nerve appears to decline only slightly between E13 and E17. The 50% decline in the number of cochlear nerve axons making functional synapses on individual NM neurons therefore is associated principally with the concurrent elimination of cochlear nerve axon branching in the NM.

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Differential expression of N-methyl-D-aspartate receptor in the cochlear nucleus of the mouse.

Glutamate is used in the cochlear nucleus as a neurotransmitter by cochlear nerve synapses and by local circuits of granule cell axons. In the present study, immunocytochemistry and in situ hybridization were used to identify different types of neurons expressing N-methyl-D-aspartate receptor subunit I (NMDAR1) in the mouse cochlear nucleus. N-Methyl-D-aspartate receptor subunit 1 was expressed in most neuronal types, but granule cells in the dorsal cochlear nucleus had little, if any, expression, unlike their heavily labeled counterparts in the small cell shell and cerebellum. The findings do not support an analogy between the dorsal cochlear nucleus and the cerebellar cortex. In the cochlear nucleus the most heavily labeled structures were dendrites in the small cell shell and superficial dorsal cochlear nucleus, including the fusiform cell apical dendrites, which are targets of granule cell axons. However, fusiform cell basal dendrites, which are the synaptic sites of cochlear nerve fibers, did not express N-methyl-D-aspartate receptor subunit 1. Thus different parts of the fusiform cells can have different subunits in their glutamate receptors. Also branches of the same cochlear nerve axons projecting to the octopus, stellate, and bushy cells of the ventral cochlear nucleus can use N-methyl-D-aspartate receptor, while their branches to fusiform cells cannot. Each cochlear nucleus neuron type has a characteristic level of N-methyl-D-aspartate receptor subunit 1 expression. Each type differs in its auditory response properties, which may depend on synaptic activities requiring different glutamate subunit patterns.

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Projections of the pontine nuclei to the cochlear nucleus in rats.

In the cochlear nucleus, there is a magnocellular core of neurons whose axons form the ascending auditory pathways. Surrounding this core is a thin shell of microneurons called the granule cell domain (GCD). The GCD receives auditory and nonauditory inputs and projects in turn to the dorsal cochlear nucleus, thus appearing to serve as a central locus for integrating polysensory information and descending feedback. Nevertheless, the source of many of these inputs and the nature of the synaptic connections are relatively unknown. We used the retrograde tracer Fast Blue to demonstrate that a major projection arises from the contralateral pontine nuclei (PN) to the GCD. The projecting cells are more densely located in the ventral and rostral parts of the PN. They also are clustered into a lateral and a medial group. Injections of anterograde tracers into the PN labeled mossy fibers in the contralateral GCD. The terminals are confined to those parts of the GCD immediately surrounding the ventral cochlear nucleus. There is no PN projection to the dorsal cochlear nucleus. These endings have the form of bouton and mossy fiber endings as revealed by light and electron microscopy. The PN represent a key station between the cerebral and cerebellar cortices, so the pontocochlear nucleus projection emerges as a significant source of highly processed information that is introduced into the early stages of the auditory pathway. The cerebropontocerebellar pathway may impart coordination and timing cues to the motor system. In an analogous way, perhaps the cerebropontocochlear nucleus projection endows the auditory system with a timing mechanism for extracting temporal information.

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Cellular regulatory mechanisms influencing the activity of the cochlear nucleus: a review.

The cochlear nucleus is the site in the auditory pathway where the primary sensory information carried by the fibres of the acoustic nerve is transmitted to the second-order neurones. According to the generally accepted view this transmission is not a simple relay process but is considered as the first stage where the decoding of the auditory information begins. This notion is based on the diverse neurone composition and highly ordered structure of the nucleus, on the complex electrophysiological properties and activity patterns of the neurones, on the activity of local and descending modulatory mechanisms and on the presence of a highly sophisticated intracellular Ca2+ homeostasis. This review puts emphasis on introducing the experimental findings supporting the above statements and on the questions which should be answered in order to gain a better understanding of the function of the cochlear nucleus.

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Tonotopic changes in 2-deoxyglucose activity in chick cochlear nucleus during hair cell loss and regeneration.

Following cochlear ablation, auditory neurons in the central nervous system (CNS) undergo alterations in morphology and function, including neuronal cell death. The trigger for these CNS changes is the abrupt cessation of eighth nerve fiber activity. Gentamicin can cause ototoxic damage to cochlear hair cells responsible for high frequency hearing. In birds, these hair cells can regenerate. Therefore, gentamicin causes a partial, yet reversible insult to the ear. It is not known how this partial hair cell damage affects excitatory input to the cochlear nucleus. We examined chick cochlear nucleus activity during hair cell loss and regeneration by measuring 2-deoxyglucose (2DG) uptake. Normal animals showed a rostral to caudal gradient of 2DG activity, with higher activity in caudal regions. When hair cells are damaged (2, 5 days), 2DG uptake is decreased in cochlear nucleus. When hair cells regenerate (9, 16, 28 days), 2DG uptake returns to control levels. This decrease and subsequent return of activity only occurs in the rostral, high frequency region of the cochlear nucleus. No changes are seen in the caudal, low frequency region. These results suggest that changes in activity of cochlear nucleus occur at a similar time course to anatomical changes in the cochlea.

Acoustic Stimulation↗

Putative commissural and collicular axo-somatic terminals on neurons of the rat ventral cochlear nucleus.

The type of synaptic terminals from the cochlear nucleus and inferior colliculus that terminate in the contralateral ventral cochlear nucleus are not known. These terminals were studied with the electron microscope and immunogold after injection of wheat germ agglutinin conjugated to horseradish peroxidase into the inferior colliculus or into the cochlear nucleus. The tracer anterogradely labelled boutons onto the main neurons of the contralateral ventral cochlear nucleus. Most of these cells (95%) were glycine immuno-negative and represent excitatory neurons. After injection of the tracer into the contralateral inferior colliculus few anterogradely labelled boutons were seen on spherical and multipolar cells of type II in the anteroventral cochlear nucleus. Rare labelled boutons were present on multipolar cells of type I and II, globular neurons and octopus cells in the posteroventral cochlear nucleus. After injection into the contralateral dorsal and ventral cochlear nucleus labelled boutons were seen more frequently than after injection into the inferior colliculus. These terminals contacted most of large neurons, especially multipolar cells of type II and less frequently of type I. Also globular and spherical cells were contacted by commissural terminals. Octopus cells received less frequently putative commissural terminals. Most boutons contained pleomorphic vesicles and stored GABA. A lower number of boutons with pleomorphic and flat vesicles contained glycine and sometimes GABA, both inhibitory neurotransmitters. Few boutons containing round vesicles were immuno-negative for both glycine and GABA, and were considered putative commissural excitatory terminals. The latter often contacted glycinergic neurons of type II so that also these terminals might elicit an inhibition with at least a disynaptic mechanism after contralateral stimulation.

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Functional characteristics of spontaneously active neurons in rat dorsal cochlear nucleus in vitro.

1. The cochlear nucleus of rat brain stem slices was explored with extracellular microelectrodes to determine the distribution and characteristics of spontaneously active neurons. 2. In mapping experiments few spontaneously active neurons were found in anteroventral or posteroventral divisions of the cochlear nucleus. In contrast, spontaneously active neurons (N = 648) were widely distributed in the dorsal cochlear nucleus (DCN), especially its more superficial part. The density (neurons per penetration) was greatest 100-400 microns from the lateral surface of DCN, corresponding approximately to the fusiform soma layer and closely adjacent portions of the molecular and deeper regions. In penetrations with active neurons as many as 13 were found, with a mean of 4.3 neurons per penetration. Activity was found along the entire dorsomedial-ventrolateral extent of the nucleus, across the tonotopic representation. 3. Most neurons were readily categorized according to the spike interval pattern as regular (40%), bursting (30%), or irregular (30%). Regular and bursting patterns were highly stable, but few bursting neurons were found in relatively inactive slices. Although there was extensive overlap in location, bursting neurons were significantly closer to the lateral edge of the slice. Also, they were more likely to have initially negative action potentials than regular or irregular neurons. 4. A high density of spontaneous firing, including regular, bursting, and irregular patterns, was observed in slices containing only DCN and adjacent fiber tracts, with other nuclear structures trimmed away. 5. When the K+ concentration of the perfusion medium was decreased from 6.25 to 3.25 mM firing rates of regular neurons decreased moderately without changes in pattern. In contrast, firing rates of most bursting and irregular neurons showed large increases, and bursts were prolonged. 6. When the K+ concentration was increased from 6.25 to 9.25 or 12.25 mM regular neurons showed moderate increases in rate without changes in pattern. Effects on firing rates differed among bursting and irregular neurons, but bursts usually increased in frequency and decreased in duration, and irregular neurons showed some burst firing. 7. When Ca2+ was decreased to 0.2 mM and Mg2+ increased to 3.8 or 7.8 mM regular neurons did not change in pattern of firing although firing rates increased or decreased moderately. Bursting neurons showed large increases in the durations of the bursts. Firing rates of bursting neurons usually increased during 0.2 mM Ca2+ -3.8 mM Mg2+ but typically decreased, after an initial rise, during 0.2 mM Ca2+ -7.8 mM Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS)

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Distribution and origin of serotoninergic afferents to guinea pig cochlear nucleus.

The distribution of serotoninergic fibers in the guinea pig cochlear nucleus was studied with serotonin immunohistochemistry. In addition, the origin of the serotoninergic fibers was determined by combining the retrograde transport of wheat germ agglutinin-apohorseradish peroxidase (gold conjugated) with serotonin immunohistochemistry. Immunoreactivity was present in varicose and nonvaricose fibers that were unevenly distributed throughout the cochlear nucleus. The fibers were most prominent in the superficial layers of the dorsal cochlear nucleus and the anterior spherical cell area of the anteroventral cochlear nucleus. Although less prominent, serotonin-positive fibers were also present in the remaining part of the anteroventral cochlear nucleus and the posteroventral cochlear nucleus. A few positive fibers were present in the auditory nerve root and the dorsal and intermediate acoustic striae. Double-labeled cells were found throughout the rostral-caudal extent of the serotoninergic system from the caudal linear nucleus to the nucleus raphe pallidus. However, most were confined to the dorsal (52%) and median (18%) raphe nuclei. Some serotoninergic cell groups contained retrogradely labeled cells that were not serotonin immunoreactive, indicating nonauditory afferents to cochlear nucleus containing other neurotransmitter substances. Serotonin may tonically modulate auditory processing within the cochlear nucleus as well as influence certain ascending auditory pathways. Most of the serotonin in the cochlear nucleus comes from superior raphe nuclei that also project to basal ganglia motor systems and limbic structures. Therefore, the effect of serotonin on the cochlear nucleus may be related to level of arousal or behavioral state.

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Loss of cochlear nucleus neurons following aminoglycoside antibiotics or cochlear removal.

This study compared the effects of aminoglycoside ototoxicity and surgical ablation of the cochlea in infancy on the survival of neurons in the rat cochlear nucleus (CN). Ototoxicity was induced by a single, systemic dose of gentamicin sulfate and furosemide on postnatal day 6 (P6), P7, or P10, and assessed by the elevation of auditory brain stem response thresholds, as described in a companion paper. Unilateral cochlear removals were performed under Saffan anesthesia on P6, P9, and P12. Rats were painlessly sacrificed in adulthood, and the formalin-perfused brains and cochleas were embedded in wax, sectioned, and stained. Ototoxic treatment at P6 through P10 did not reduce neuron counts in the CN. Cochlear removal at P6 resulted in a 40% loss of CN neurons, but removal at P12 did not result in CN neuron loss. These data suggest that the critical period for the dependence of CN neurons on afferent input from the cochlea ends at the same time that susceptibility to aminoglycoside ototoxicity begins.

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Descending projections from auditory brainstem nuclei to the cochlea and cochlear nucleus of the guinea pig.

Projections from auditory brainstem nuclei to the cochlea and cochlear nuclei in the guinea pig were studied by injection of two retrograde fluorescent neuronal tracers. For seven experiments fast blue was injected into the scala tympani of one cochlea and diamidino yellow was injected into dorsal or anteroventral cochlear nucleus of the same side. The results show that the efferent projections to the cochlea and cochlear nucleus generally form two separate neuronal systems even though they share many common nuclei of origin. The largest projections to the cochlear nucleus come bilaterally from the lateral and ventral nuclei of the trapezoid body. Other nuclei, the lateral superior olive, the ventral nucleus of the lateral lemniscus, the dorsomedial periolivary nuclei, and the medial nucleus of the trapezoid body showed an ipsilateral bias in their projections to the cochlear nucleus. An upper limit of 3.5% of the medial system olivocochlear efferent neurones projecting to the cochlea were labelled with both diamidino yellow and fast blue, suggesting that few efferent neurones projecting to the cochlea send collaterals to the cochlear nucleus in this species. However, the site of medial system olivocochlear efferent collateral terminations is the granule cell area for the cat, mouse, and gerbil. When diamidino yellow was injected in the superficial layers of the cochlear nucleus, including the superficial granule cell layer of the ventral cochlear nucleus, approximately 3.6% of medial system olivocochlear efferents projecting to the cochlea sent collaterals to the cochlear nucleus. In three animals fast blue was injected into the cochlear nucleus and diamidino yellow into the cochlea. These experiments revealed a greater proportion of the medial system olivocochlear efferents projecting to the cochlea sending collaterals to the cochlear nucleus, but this proportion was still less than 10%. These results were confirmed by the extracellular injection of horseradish peroxidase into the intraganglionic spiral bundle. Only three medial system olivocochlear efferents were observed to send collaterals to the cochlear nucleus. This number was less than 10% of all labelled medial system fibres. Although these experiments suggest that in the guinea pig the number of olivocochlear efferents sending collaterals to the cochlear nucleus is considerably smaller than is found for the cat, mouse, and gerbil, it is not possible with the current experimental procedures to conclude whether the results are due to species or methodological differences.

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The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: horseradish peroxidase labelling of identified cell types.

Golgi impregnations of the posterior part of the cat's anteroventral cochlear nucleus have revealed two types of neurons, bushy cells with short bush-like dendrites and stellate cells with long, tapered processes; Nissl stains have revealed globular and multipolar cell bodies with dispersed and clumped ribosomal patterns, respectively. In the present study, we injected horseradish peroxidase into the trapezoid body. Ipsilaterally, retrograde, diffuse labelling of neurons, presumably through damaged fibers, yielded Golgi-like profiles of numerous bushy cells with typical dendrites and with thick axons projecting toward the trapezoid body. Stellate cells were almost never labelled in this way. Anterograde diffuse labelling of thick axons demonstrated calyx endings in the contralateral medial nucleus of the trapezoid body. In the electron-microscope, the perikarya of diffusely-filled bushy neurons were found to have the dispersed ribosomal pattern and the kinds of synaptic endings typical of globular cells, including large profiles of end-bulbs from cochlear nerve axons. After injections restricted to the medial trapezoid nucleus, granularly-labelled cells in the cochlear nucleus were almost completely confined to the contralateral side; Nissl counterstaining showed them to be globular cells in the posterior part of the anteroventral cochlear nucleus. After larger injections, involving surrounding regions of the superior olivary complex, granular labelling occurred throughout the ventral cochlear nucleus on both sides. There is also evidence that stellate cells in Golgi impregnations correspond to multipolar cell bodies in Nissl stains. We conclude that bushy cells typically correspond to globular cells, which receive end-bulbs from the cochlea and send thick axons to the contralateral medial trapezoid nucleus, where they form calyces on principal cells. Principal cells, in turn, are known to project to the lateral superior olive and to one of the nuclei of origin of the crossed olivo-cochlear bundle, which feeds back to the cochlea. In this circuit, correlations between synaptic patterns and particular physiological signal transfer characteristics can be suggested. These could be related to binaural intensity interactions in the lateral superior olive and to a regulatory loop involving the olivo-cochlear bundles.

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Development of N-methyl-D-aspartate receptor subunit immunoreactivity in the neonatal gerbil cochlear nucleus.

The distribution of immunoreactivity for the ionotropic N-methyl-D-aspartate (NMDA) receptor subunits was mapped in the cochlear nucleus of postnatal day (P) 7, P14, P21, and P28 gerbils. Frozen sections and serial plastic sections of tissue were incubated with antibodies to NMDAR1 (NR1), NMDAR2A (NR2A), NMDAR2A/B (NR2A/B), and NMDAR2B (NR2B). An overall diffuse stain was noted at P7 for NR1 and NR2A/B. Staining of neuronal somata in the dorsal cochlear nucleus molecular layer and fusiform cell layer, the posteroventral cochlear nucleus octopus cell area, and the anteroventral cochlear nucleus increased from P7 to P28. Staining of the neuropil (the unresolved mass of processes and axons, excluding only neuronal somata and distinctly stained proximal dendrites) of the deep dorsal cochlear nucleus and posteroventral cochlear nucleus showed a steady decrease, while molecular layer neuropil remained moderately stained. The NR2A antibody produced a distinctive staining of dendrites in the dorsal cochlear nucleus deep and fusiform cell layers seen first at P14 with increasing dendritic lengths stained at P21 and P28. Giant neurons of the deep dorsal cochlear nucleus were the most conspicuous somata stained by the NR2A. Their stained dendrites spanned much of the dorsal cochlear nucleus deep and fusiform cell layers and even extended into the octopus cell area of the posteroventral cochlear nucleus. Dendritic staining was also present in caudal and rostral posteroventral cochlear nucleus, first distinguishable at P14 and becoming increasingly strong. The Chemicon polyclonal NR2B antibody produced glial staining especially prominent in the caudal posteroventral cochlear nucleus and the dorsal cochlear nucleus fusiform cell layer, most intense at P7 and subsequently decreasing, although not disappearing, in all areas through P28. The Molecular Probes (Eugene, OR) polyclonal NR2B produced a light granular staining pattern over a number of somata but no glial staining. Neuropil staining was not prominent with either NR2B antibody. Differences in changes of neonatal immunoreactivity patterns in different populations of cochlear nucleus neuronal somata and dendrites for NR1, NR2A, NR2A/B, and NR2B suggest that alterations in some receptor composition is occurring over the period spanning the onset of hearing.

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Noradrenalin enhances the activity of cochlear nucleus neurons in the rat.

The cochlear nucleus of rats is heavily innervated by noradrenergic fibres from the locus coeruleus. The physiological meaning of this innervation is poorly understood. Therefore, iontophoretically applied noradrenalin was tested on single neurons of the cochlear nucleus in urethane-anaesthetized rats. Iontophoresis of noradrenalin had a dual effect. During application noradrenalin led to moderate inhibition of tone-evoked activity in 37% of the tested neurons. In contrast, approximately 20-30 s after the onset of iontophoresis a long-lasting increase in discharge activity was found in most neurons. Data from iontophoresis of the alpha1-receptor agonist phenylephrine and the alpha2-receptor agonist clonidine suggest that the fast moderate inhibition is mediated by alpha2-receptors while the pronounced long-lasting elevated neuronal firing is mediated by alpha1-receptors. However, these data do not exclude the possibility that part of the response to noradrenalin is also mediated by beta-receptors. Electrical stimulation of the locus coeruleus resulted in an increase in discharge activity comparable with iontophoresis of noradrenalin or phenylephrine. Thus, activation of the locus coeruleus predominantly increases spontaneous and tone-evoked neuronal firing in the cochlear nucleus of the rat. This alpha-receptor-mediated enhanced discharge activity may serve to increase the sensitivity of acoustic processing mechanisms or to lower the threshold for short-latency acoustic reflexes.

Acoustic Stimulation↗

Anatomical variations of landmarks for implantation at the cochlear nucleus.

A knowledge of the microanatomy of the cochlear nucleus complex and its variations is essential for successful implantation and for the design of stimulation devices. One hundred cerebellopontine angle specimens were dissected under surgical conditions using the Zeiss NC31 surgical microscope. The topographical anatomy of the exit of the vestibulocochlear nerve, the cochlear nucleus and the surface of the medulla and their relation to the surrounding structures was recorded and measured. The mean distances between the exits of the VIIth and VIIIth cranial nerves were 4.7 +/- 0.9 mm, between the VIIth and IXth 6.3 +/- 1.2 mm and between the VIIIth and IXth 5.5 +/- 1.0 mm. The visible area of the cochlear nucleus covered a square of 10.0 +/- 2.9 by 3.3 +/- 1.0 mm. A major AICA-loop had to be re-routed in 17 per cent of specimens. The taenia of the choroid plexus was present in 92 per cent and had to be cut in 51 per cent in order to enter the foramen of Luschka, that had a mean size of 3.5 by 2.0 mm. It was wide open in 24 per cent, open only after incision of the arachnoid in 53 per cent, functionally closed but opened by extensive dissection in 18 per cent and anatomically occluded in five per cent of the specimens. The typical straight vein at the cochlear nucleus leading to the entrance of the foramen of Luschka was found in 76 per cent of specimens. Constant anatomical landmarks are very helpful for finding the cochlear nucleus, but variations may endanger dissection and implantation in a remarkable number of cases.

Brain Stem↗