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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.

Animals↗

A functional point-neuron model simulating cochlear nucleus ideal onset responses.

Cochlear nucleus neurons revealing ideal onset (OI)-type peri-stimulus time histograms (PSTH) encode temporal features of acoustic stimuli with very high precision. These neurons are therefore assumed to be involved in the recognition of natural sounds with temporally varying envelopes such as speech. A functional point-neuron model is presented here for the simulation of OI-unit responses found in cochlear nucleus octopus cells. The model assumes a biphasic response of the membrane potential to a current impulse, the membrane impulse response, and a dynamic spike-blocking mechanism. The predicted responses to pure tones at low and high frequencies, injected current steps, and amplitude modulated tones are compared to recordings from the literature. The model accounts for the main response properties in the data using the same small set of parameters for all experimental conditions. The assumed biphasic shape of the membrane impulse response, reflecting a higher sensitivity to stimulus transients and fast changes relative to sustained stimulus portions, allows for a description of OI-unit responses that cannot be accounted for by a coincidence detector model with an integrate-to-threshold dynamic. The presented functional model may be useful as a processing module in more complex models of auditory signal processing and perception.

Acoustic Stimulation↗

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.

Animals↗

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)

Animals↗

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.

Animals↗

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.

Animals↗

Redistribution of synaptic AMPA receptors at glutamatergic synapses in the dorsal cochlear nucleus as an early response to cochlear ablation in rats.

This study investigated whether unilateral deafferentation of the presynaptic neuron is key in the control of morphology and the subunit composition and expression of AMPA type glutamate receptors (GluRs) in neurons of the dorsal cochlear nucleus (DCN). Data showed that there are morphological changes at the postsynaptic sites which precede presynaptic changes at the auditory nerve (AN) synaptic ending in response to peripheral damage, in particular that the postsynaptic densities (PSD) of the AN on fusiform cells (FC) are thicker after denervation. Moreover, GluR2, GluR3 and GluR4 AMPA receptor subunits were redistributed, not only at the synapse of FCs receiving direct contact with the AN, but also at the glutamatergic synapse of the parallel fibers on FC and on cartwheel cells (CwC) which are indirectly innervated by the AN. Interestingly, the same synapses in the DCN contralateral to the lesion and with a normal AN synaptic input also redistributed AMPA receptor subunits at the synapse in respond to deafferentation. In these synapses, there was an increase of immunogold labeling for GluR2/3 subunits but not for GluR2 at 2 days after deafferentation.

Analysis of Variance↗

Wisteria floribunda lectin is associated with specific cell types in the ventral cochlear nucleus of the gerbil, Meriones unguiculatus.

The cochlear nucleus is made up of a number of diverse cell types with different anatomical and physiological properties. A plant lectin, Wisteria floribunda agglutinin, that recognizes specific carbohydrate residues in the extracellular matrix binds to some cell types in the ventral cochlear nucleus but not to cells in the dorsal cochlear nucleus. In the ventral cochlear nucleus, the most intensely labeled cells are octopus cells, a subset of multipolar cells and cochlear root neurons. The multipolar cells that are labeled may correspond to the population that projects to the inferior colliculus.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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↗

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.

Animals↗

Commissural glycinergic inhibition of bushy and stellate cells in the anteroventral cochlear nucleus.

Synaptic inputs from one cochlear nucleus (CN) to the other can play an important role in modulating the activity of CN neurons. Using the isolated whole brain preparation of the guinea pig, we tested the effects of electrical stimulation of the contralateral auditory nerve (AN) on intracellularly recorded and stained neurons of the anteroventral cochlear nucleus. Stimulation of the contralateral AN evoked only inhibitory postsynaptic potentials (IPSPs) in 63% of recorded neurons, including bushy and stellate cells. The latency of most IPSPs (88%) was in the range 3.3-7.6 ms, consistent with mono- and disynaptic transmission from the contralateral CN. The IPSPs had an average amplitude of 2.6 +/- 1.9 mV and were blocked by strychnine suggesting their glycinergic nature. These data, together with our similar findings in other CN subdivisions, indicate that principal cells of the CN contribute to binaural interactions at earliest stages of acoustic processing.

Animals↗

Single unit recordings in the auditory nerve of congenitally deaf white cats: morphological correlates in the cochlea and cochlear nucleus.

It is well known that experimentally induced cochlear damage produces structural, physiological, and biochemical alterations in neurons of the cochlear nucleus. In contrast, much less is known with respect to the naturally occurring cochlear pathology presented by congenital deafness. The present study attempts to relate organ of Corti structure and auditory nerve activity to the morphology of primary synaptic endings in the cochlear nucleus of congenitally deaf white cats. Our observations reveal that the amount of sound-evoked spike activity in auditory nerve fibers influences terminal morphology and synaptic structure in the anteroventral cochlear nucleus. Some white cats had no hearing. They exhibited severely reduced spontaneous activity and no sound-evoked activity in auditory nerve fibers. They had no recognizable organ of Corti, presented >90% loss of spiral ganglion cells, and displayed marked structural abnormalities of endbulbs of Held and their synapses. Other white cats had partial hearing and possessed auditory nerve fibers with a wide range of spontaneous activity but elevated sound-evoked thresholds (60-70 dB SPL). They also exhibited obvious abnormalities in the tectorial membrane, supporting cells, and Reissner's membrane throughout the cochlear duct and had complete inner and outer hair cell loss in the base. The spatial distribution of spiral ganglion cell loss correlated with the pattern of hair cell loss. Primary neurons of hearing-impaired cats displayed structural abnormalities of their endbulbs and synapses in the cochlear nucleus which were intermediate in form compared to normal and totally deaf cats. Changes in endbulb structure appear to correspond to relative levels of deafness. These data suggest that endbulb structure is significantly influenced by sound-evoked auditory nerve activity.

Animals↗

Effects of cochlear ablation on muscarinic acetylcholine receptor binding in the rat cochlear nucleus.

Cholinergic synapses in the cochlear nucleus (CN) have been reported to modulate spontaneous activity via muscarinic acetylcholine receptors. In this study, muscarinic receptor binding was measured as specific binding of 1-[N-methyl-(3)H]scopolamine in CN regions of control rats and 7 days, 1 month, and 2 months after unilateral cochlear ablation. In control rats, the strongest binding was found in granular regions, followed in order by fusiform soma, molecular, and deep layers of the dorsal cochlear nucleus (DCN), with much lower binding in the anteroventral CN (AVCN) and posteroventral CN (PVCN). After unilateral cochlear ablation, binding in the AVCN, PVCN, and their associated granular regions on the lesion side became progressively greater than on the control side through 2 months after lesion. A significant asymmetry, with binding higher on the lesion side, was also found in the DCN fusiform soma layer at 7 days, and there and in the DCN deep layer at 1 and 2 months after lesion. There was also evidence of increased binding on the control side in most CN regions. By contrast, binding in the ipsilateral facial nucleus decreased, compared with the control side, by 7 days after the lesion and showed some recovery toward symmetry by 2 months after lesion, and there was no evidence for contralateral changes. These muscarinic receptor binding changes reflect receptor plasticity after loss of auditory nerve innervation. Such plasticity may underlie some of the central auditory functional changes that occur following peripheral lesions, such as tinnitus and hyperacusis.

Animals↗