Attenuation of noise-induced hyperactivity in the dorsal cochlear nucleus by pre-treatment with MK-801.

It has previously been hypothesized that hyperactivity of central auditory neurons following exposure to intense noise is a consequence of synaptic alterations. Recent studies suggest the involvement of NMDA receptors in the induction of this hyperactive state. NMDA receptors can mediate long term changes in the excitability of neurons through their involvement in excitotoxic injury and long term potentiation and depression. In this study, we examined the effect of administering an NMDA receptor blocker on the induction of hyperactivity in the dorsal cochlear nucleus (DCN) following intense sound exposure. Our prediction was that if hyperactivity induced by intense sound exposure is dependent on NMDA receptors, then blocking these receptors by administering an NMDA receptor antagonist just before animals are exposed to intense sound should reduce the degree of hyperactivity that subsequently emerges. We compared the levels of hyperactivity that develop in the DCN after intense sound exposure to activity recorded in control animals that were not sound exposed. One group of animals to be sound exposed received intraperitoneal injection of MK-801 twenty minutes preceding the sound exposure, while the other group received injection of saline. Recordings performed in the DCN 26-28 days post-exposure revealed increased response thresholds and widespread increases in spontaneous activity in the saline-treated animals that had been sound exposed, consistent with earlier studies. The animals treated with MK-801 preceding sound exposure showed similarly elevated thresholds but an attenuation of hyperactivity in the DCN; the attenuation was most robust in the high frequency half of the DCN, but lower levels of hyperactivity were also found in the low frequency half. These findings suggest that NMDA receptors are an important component of the hyperactivity-inducing mechanism following intense sound exposure. They further suggest that blockade of NMDA receptors may offer a useful therapeutic approach to preventing induction of noise-induced hyperactivity-related hearing disorders, such as tinnitus and hyperacusis.

Cochlear ablation effects on amino acid levels in the chinchilla cochlear nucleus.

Inner ear damage can lead to hearing disorders, including tinnitus, hyperacusis, and hearing loss. We measured the effects of severe inner ear damage, produced by cochlear ablation, on the levels and distributions of amino acids in the first brain center of the auditory system, the cochlear nucleus. Measurements were also made for its projection pathways and the superior olivary nuclei. Cochlear ablation produces complete degeneration of the auditory nerve, which provides a baseline for interpreting the effects of partial damage to the inner ear, such as that from ototoxic drugs or intense sound. Amino acids play a critical role in neural function, including neurotransmission, neuromodulation, cellular metabolism, and protein construction. They include major neurotransmitters of the brain - glutamate, glycine, and γ-aminobutyrate (GABA) - as well as others closely related to their metabolism and/or functions - aspartate, glutamine, and taurine. Since the effects of inner ear damage develop over time, we measured the changes in amino acid levels at various survival times after cochlear ablation. Glutamate and aspartate levels decreased by 2weeks in the ipsilateral ventral cochlear nucleus and deep layer of the dorsal cochlear nucleus, with the largest decreases in the posteroventral cochlear nucleus (PVCN): 66% for glutamate and 63% for aspartate. Aspartate levels also decreased in the lateral part of the ipsilateral trapezoid body, by as much as 50%, suggesting a transneuronal effect. GABA and glycine levels showed some bilateral decreases, especially in the PVCN. These results may represent the state of amino acid metabolism in the cochlear nucleus of humans after removal of eighth nerve tumors, which may adversely result in destruction of the auditory nerve. Measurement of chemical changes following inner ear damage may increase understanding of the pathogenesis of hearing impairments and enable improvements in their diagnosis and treatment.

Effects of cochlear ablation on amino acid concentrations in the chinchilla posteroventral cochlear nucleus, as compared to rat.

Using a microchemical approach, we measured changes of amino acid concentrations in the chinchilla caudal posteroventral cochlear nucleus (PVCN) after cochlear ablation to determine to what extent slow decreases of glutamate and aspartate concentrations after carboplatin treatment resulted from slower effects of cochlear damage in chinchillas than in rats and guinea pigs, as opposed to effects of carboplatin treatment being slower than those of cochlear ablation. Our results indicate that both factors are involved: decreases of glutamate and aspartate concentrations after cochlear ablation are much slower in chinchillas than in rats and guinea pigs, but they are much faster than the decreases after carboplatin treatment. Further, aspartate and glutamate concentrations in the chinchilla caudal PVCN decreased by larger amounts after cochlear ablation than in rats or guinea pigs, and there was a transient increase of aspartate concentration at short survival times. Detailed mapping of amino acid concentrations in the PVCN of a chinchilla with 1 month survival after cochlear ablation and a rat with 7 days' survival indicated that the reductions of glutamate and aspartate occurred throughout the PVCN but were somewhat larger in ventral and caudal parts in chinchilla. Any decreases in the adjacent granular region were very small. There were also sustained bilateral decreases in concentrations of other amino acids, notably GABA and glycine, in the caudal PVCN of cochlea-ablated chinchillas but not rats. The effects of cochlear ablation on the concentrations of most of these other amino acids in chinchilla caudal PVCN differed from those of carboplatin treatment. Thus, although a major effect of auditory nerve damage on the cochlear nucleus-decreases of glutamate and aspartate concentrations-occurs across species and types of lesions, the details of timing and magnitude and the effects on other amino acids can vary greatly.

Origin of hyperactivity in the hamster dorsal cochlear nucleus following intense sound exposure.

This study sought to determine whether maintenance of noise-induced dorsal cochlear nucleus (DCN) hyperactivity depends on descending projections. Twenty-two hamsters were exposed under anesthesia to a 10-kHz tone at 125-130 dB SPL for 4 hr, and another 21 unexposed animals served as controls. After approximately 4-6 weeks of recovery, surgical transections were made to isolate the DCN from its adjacent brainstem structures. Spontaneous multiunit activity was recorded from the DCN surface 30-40 min after the surgical manipulations. Spontaneous rates were derived from the recording sites of the DCN along its mediolateral axis for each animal, yielding average spontaneous rates for both control and exposed groups. Histology was performed to assess the degree of sectioning of descending fiber tract connections to the cochlear nucleus, via the acoustic striae route, subpeduncular route, trapezoid body route, and ventral route of the olivocochlear bundle connection. The results showed that complete or nearly complete transections of descending inputs did not affect significantly the magnitude of DCN hyperactivity. However, this manipulation triggered a lateral shift of the peak mean rate, suggesting that descending inputs may play a modulatory role on the profile of DCN hyperactivity. Indeed, exposed animals with transection of only the strial route of entry manifested a level of hyperactivity much higher than that observed in exposed animals in which no sections were performed. This enhancement of DCN hyperactivity was weakened by damage to the subpeduncular or trapezoid routes of input, suggesting that the dorsally located inputs may have an inhibitory effect on DCN hyperactivity.

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine.

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Amino acid concentrations in rat cochlear nucleus and superior olive.

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

Sodium pentobarbital abolishes bursting spontaneous activity of dorsal cochlear nucleus in rat brain slices.

There is evidence that pentobarbital, a commonly used anesthetic, can affect neuronal activity, but its effects on particular neurons of the dorsal cochlear nucleus (DCN) are not well known. Bursting (complex spiking) spontaneous activity has been observed in the DCN in brain slice preparations and in recordings from unanesthetized decerebrate animals, but seldom in experiments with anesthetized animals. This study investigated the effects of pentobarbital on spontaneous activity in the DCN in brain slices. Most extracellularly recorded bursting neurons decreased firing rates and reversibly changed their firing to simple spiking with irregular intervals during pentobarbital. Some reversibly stopped firing after the change to an irregular pattern. Most neurons with regular spontaneous activity (simple spiking) showed decreased firing rates and more irregular intervals during pentobarbital. The results also suggest some involvement of gamma-aminobutyric acid type A receptors in the pentobarbital effects.

Effects of high-potassium-induced depolarization on amino acid chemistry of the dorsal cochlear nucleus in rat brain slices.

High K+ was used to depolarize glia and neurons in order to study the effects on amino acid release from and concentrations within the dorsal cochlear nucleus (DCN) of brain slices. The release of glutamate, gamma-aminobutyrate (GABA) and glycine increased significantly during exposure to 50 mM K+, while glutamine and serine release decreased significantly during and/or after exposure, respectively. After 10 min of exposure to 50 mM K+, glutamine concentrations increased in all three layers of DCN slices, to more than 5 times the values in unexposed slices. In the presence of a glutamate uptake blocker, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC), glutamine concentrations in all layers did not increase as much during 50 mM K+. Similar but smaller changes occurred for serine. Mean ATP concentrations were lower in 50 mM K(+)-exposed slices compared to control. The results suggest that depolarization, such as during increased neural activity, can greatly affect amino acid metabolism in the cochlear nucleus.

Metabolism of the dorsal cochlear nucleus in rat brain slices.

In vitro brain slices of the cochlear nucleus have been used for electrophysiological and pharmacological studies. More information is needed about the extent to which the slice resembles in vivo tissue, since this affects the interpretation of results obtained from slices. In this study, some chemical parameters of the dorsal cochlear nucleus (DCN) in rat brain slices were measured and compared to the in vivo state. The activities of malate dehydrogenase and lactate dehydrogenase were reduced in some DCN layers of incubated slices compared to in vivo brain tissue. The activities of choline acetyltransferase and acetylcholinesterase were increased or unchanged in DCN layers of slices. Adenosine triphosphate (ATP) concentrations for in vivo rat DCN were similar to those of cerebellar cortex. Compared with in vivo values, ATP concentrations were decreased in the DCN of brain slices, especially in the deep layer. Vibratome-cut slices had lower ATP levels than chopper-cut slices. Compared with the in vivo data, there were large losses of aspartate, glutamate, glutamine, gamma-aminobutyrate and taurine from incubated slices. These amino acid changes within the slices correlated with the patterns of release from the slices.

Reduced spontaneous activity in the dorsal cochlear nucleus of Scn8a mutant mice.

Spontaneous activity was recorded in the dorsal cochlear nucleus of brain slices from mice homozygous for the med-J and jolting mutations in the neuronal sodium channel alpha-subunit Scn8a. Densities of spontaneously active neurons in slices from both mutants were significantly lower than in control slices. Spontaneous firing patterns with bursts of action potentials were recorded from approximately 50% of the neurons in control slices, but the typical bursting patterns were not observed in neurons of med-J and jolting mouse slices. The results suggest that this voltage-gated sodium channel is essential for the spontaneous bursting firing of cochlear nucleus cartwheel neurons. This mutant animal model may be useful for the study of the functional roles of cochlear nucleus neurons.

Glutamergic transmission of neuronal responses to carbachol in rat dorsal cochlear nucleus slices.

This study found that glutamate receptor antagonists block the excitatory effects of carbachol, a cholinergic agonist, on bursting neurons in the dorsal cochlear nucleus of rat brain slices. Among antagonists for glutamate receptor subtypes, those for non-N-methyl-D-aspartate ionotropic glutamate receptors were more potent than those for N-methyl-D-aspartate receptors. The glutamate receptor antagonists did not block the effects of carbachol on regularly firing neurons in the dorsal cochlear nucleus of the same slices. Antagonists for GABA or glycine receptors did not alter the effects of carbachol on bursting neurons. Effects of carbachol on bursting activity could be mimicked by application of glutamate or its agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, whose effects were not blocked by synaptic blockade. During carbachol application, increased release of glutamate and glycine from the dorsal cochlear nucleus part of brain slices was measured using high-performance liquid chromatography. Release of other amino acids showed no significant change. The results suggest that, in rat dorsal cochlear nucleus, cholinergic effects on regular and bursting spontaneous firing occur through different mechanisms. Cholinergic effects on regular neurons (which include fusiform cells) are direct, through muscarinic receptors. Cholinergic effects on bursting neurons (which include cartwheel cells) are indirect and involve glutamatergic neurotransmission, mostly via non-N-methyl-D-aspartate ionotropic receptors. The granule cell-parallel fiber pathway may be involved in this glutamatergic transmission.

Immunolocalization of alpha4 and alpha7 subunits of nicotinic receptor in rat cochlear nucleus.

The rat cochlear nucleus (CN) is known to receive cholinergic input. To investigate the prevalence of nicotinic acetylcholine receptor (nAChR), immunohistochemistry for alpha4 and alpha7 subunits, which represent nAChRs with high binding affinities for nicotine and alpha-bungarotoxin, respectively, was performed on perfusion-fixed rat brain sections. Microscopic observations and densitometric measurements show dense labeling for alpha7 but not alpha4. Within the CN, alpha7 receptors are found in all subregions, with relatively high densities in granular regions. The distribution of alpha7 within the CN appears to correlate more closely with that of acetylcholinesterase than with mAChR or choline acetyltransferase. Our results suggest a role of nicotinic cholinergic transmission in the rat CN associated with high affinity for alpha-bungarotoxin.

Astrocyte reaction in the rat vestibular nuclei after unilateral removal of Scarpa's ganglion.

Unilateral vestibular ganglionectomy (UVG) results in a complete degeneration of vestibular nerve fibers and terminals in the ipsilateral vestibular nuclear complex (VNC). A subsequent glial reaction may affect the activities of VNC neurons and thereby influence compensation for lesion-induced vestibular disorders. Expression of glial fibrillary acidic protein (GFAP), a specific marker for reactive astrocytes, was demonstrated immunohistochemically in the rat VNC at 7, 14, and 35 days after UVG. An increased GFAP-positive astrocytic response was evident at 7 days after lesion in all the VNC regions on the lesioned side and in some regions on the unlesioned side and remained through 35 days. The glial response included hypertrophy, which was more prominent at 7 days than at 14 days or 35 days, and proliferation, more prominent at the later times, of GFAP-positive astrocytes. Astrocytic projections around VNC neuron somata and proximal dendrites increased in number and became thicker and more elongated, especially at 14 days, in the lateral vestibular nucleus. It is suggested that UVG results in a bilateral astrocytic reaction in the VNC that would affect the subsequent compensation.

Vesicular acetylcholine transporter in the rat cochlear nucleus: an immunohistochemical study.

After being synthesized in the cytoplasm of axon terminals, acetylcholine is packaged into synaptic vesicles by a proton-dependent transporter, vesicular acetylcholine transporter (VAChT). Localization of VAChT is restricted to cholinergic neurons, especially their terminals. We used an anti-VAChT antibody from INCSTAR to localize cholinergic terminals in the rat cochlear nucleus (CN), an important brainstem auditory center. VAChT immunoreactivity in the rat CN appears as labeled puncta and a few connecting fibers. In ventral CN (VCN), VAChT-labeled puncta are closely associated with somatic profiles of medium to large neurons. In and near the granular regions of VCN, VAChT-labeled puncta are more diffusely scattered. In the subpeduncular corner and the medial sheet, some VAChT-labeled fibers are seen in connection with especially prominent VAChT-labeled puncta. In dorsal CN (DCN), VAChT-labeled puncta show no clear association with somata and are found in all layers. Ultrastructurally, VAChT labeling is seen in the cytoplasm and is associated with synaptic vesicle membrane of terminals with small round vesicles. Such VAChT-labeled terminals synapse with cell bodies and dendrites in the CN.(J Histochem Cytochem 47:83-90, 1998)

Changes in spontaneous neural activity in the dorsal cochlear nucleus following exposure to intense sound: relation to threshold shift.

Previous studies have shown that the dorsal cochlear nucleus exhibits increased spontaneous activity after exposure to intense sound. Such increases were apparent 1-2 months after the exposure and were generally proportional to the shift in response thresholds induced by the same exposure. The purpose of the present study was to determine whether this sound-induced increase in spontaneous activity is an early event which can be observed shortly after exposure. As in previous studies, anesthetized hamsters ranging in postnatal age from 60-70 days were exposed to a 10-kHz tone at levels between 125 and 130 dB SPL for a period of 4 h. Control animals were similarly anesthetized but were not exposed to the intense tone. Exposed animals were examined in two groups, one at 30 days after exposure, the other at 2 days after exposure. Time of exposure was adjusted so that all animals were between 90 and 100 days of age when spontaneous activity was studied electrophysiologically. The results showed that the increases in spontaneous activity, which were evident at 30 days after exposure, were not observed in animals studied 2 days after exposure. This result contrasted with the effect of the intense tone exposure on neural response thresholds. That is, the shifts in response thresholds seen 2 days after exposure were similar to those observed in animals studied 30 days after exposure. These results indicate that changes in spontaneous activity reflect a more slowly developing phenomenon and occur secondarily after induction of threshold shift.

Immunohistochemical evaluation of cholinergic neurons in the rat superior olivary complex.

The cholinergic system in the rat superior olivary complex (SOC) was evaluated by immunohistochemistry for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) and histochemistry for acetylcholinesterase (AChE). ChAT-positive somata were found mostly in the lateral superior olive (LSO) and ventral nucleus of the trapezoid body (VNTB). In the LSO, there were both rostral-caudal and medial-lateral gradients in concentration of ChAT-positive somata; the highest concentration was in the middle of the rostral-caudal extent and the most medial part. The estimated total number of ChAT-positive neurons in the LSO was similar to previous estimates of the total number of lateral olivocochlear neurons. Two groups of ChAT-positive somata were found in the VNTB: a dorsolateral group of larger, multipolar, and more darkly labeled neurons and a ventromedial group of smaller, oval, and more lightly labeled neurons, which was about 5 times as numerous. There was a caudal-to-rostral increase in number of neurons in each group. VAChT immunoreactivity, predominantly localized in puncta, was seen in LSO, VNTB, and LNTB, and, to a lesser extent, in other parts of the SOC. VAChT-positive somata were also found in the VNTB and medial LSO. This distribution pattern of VAChT was generally similar to that of ChAT. AChE labeling had a similar appearance to ChAT labeling in the VNTB but differed in the LSO, where AChE labeling was lighter and associated more with neuropil than with somata.

Effects of endogenous acetylcholine on spontaneous activity in rat dorsal cochlear nucleus slices.

We have examined the contribution of endogenous acetylcholine (ACh) release to the spontaneous firing of both regular (probably fusiform cells) and bursting neurons (probably cartwheel cells) in the dorsal cochlear nucleus (DCN) in rat brainstem slices. The muscarinic antagonists atropine, scopolamine, and tropicamide (1-2 microM) caused substantial decreases of firing rates in a majority of the neurons. Reversible acetylcholinesterase (AChE) inhibitors typically caused large transient increases in firing that decayed more slowly than responses to carbachol. The irreversible AChE inhibitor diisopropyl fluorophosphate (DFP) usually caused a sustained increase, with an initial peak followed by a gradual change to a final level higher than before DFP. Tropicamide caused large decreases in firing after DFP, confirming sustained ACh release. Both neostigmine and DFP applied after AChE inhibition by DFP sometimes elicited a transient response. We conclude that the level of sustained response to DFP is determined by the rate of endogenous ACh release, and that DFP and reversible AChE inhibitors exert an initial transient agonist effect that overlaps the initial effect of acetylcholinesterase inhibition. The slice experiments provide a model for cholinergic mechanisms in vivo, confirm that the release of endogenous ACh increases the firing rates of regular and bursting neurons in superficial DCN, and support the hypothesis that spontaneous firing of DCN neurons is sustained in part by cholinergic inputs.

Densitometric evaluation of markers for cholinergic transmission in rat superior olivary complex.

Cholinergic transmission in the rat superior olivary complex (SOC) was assessed by densitometric measurements of labeling with several markers: acetylcholinesterase (AChE) histochemistry, choline acetyltransferase (ChAT) immunohistochemistry, and muscarinic acetylcholine receptor (M35) immunohistochemistry and N-methylscopolamine (NMS) binding autoradiography, as well as its subtype 2 (m2) immunohistochemistry. The markers which may occur in cholinergic neurons (ChAT, m2 receptor and AChE) showed dense labeling in the ventral nucleus of the trapezoid body (VNTB), in line with other evidence that it contains cholinergic neuron somata. The markers which are predominantly in cholinoceptive neurons (M35 and NMS) showed less labeling in the SOC, suggesting few muscarinic cholinergic inputs. These results are compared with those for the cochlear nucleus.

Quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding in rat vestibular nuclear complex after unilateral deafferentation, with comparison to cochlear nucleus.

The distributions of non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the rat vestibular nuclear complex were estimated by quantitative autoradiography of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione and (+)-3-[3H]dizocilpine maleate binding, respectively. The binding of 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione in the vestibular nuclear complex was also compared with that in the cerebellar cortex and cochlear nucleus. Measurements were made in control rats and in rats with unilateral destruction of the inner ear and removal of the vestibular ganglion. Compared to the unlesioned side, 5-[3H]6-cyano-7-nitro-quinoxaline-2,3-dione binding in the lesioned-side vestibular nuclear complex was decreased significantly in all regions at two to four postoperative days. However, the bilateral asymmetry disappeared in most regions by 30 days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding increased in the molecular layer of the cerebellar cortex at 30 days after lesion, although there were no clear changes at two to seven days. 5-[3H]6-Cyano-7-nitro-quinoxaline-2,3-dione binding in the cochlear nucleus decreased on the lesioned side, compared to the unlesioned side, in regions receiving significant auditory nerve innervation, but increased in the molecular layer of the dorsal cochlear nucleus. (+)-3-[3H]Dizocilpine maleate binding in regions of the vestibular nuclear complex was reduced on the lesioned side, compared to the unlesioned side, after deafferentation, with the largest reductions usually at 30 postoperative days. It is suggested that: (i) non-N-methyl-D-aspartate receptors are involved in synaptic transmission for both vestibular and auditory nerve fibers, while the involvement of N-methyl-D-aspartate receptors is less certain; (ii) unilateral deafferentation of the vestibular nuclear complex can result in bilateral asymmetries for non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors, which are most prominent at earlier and later survival times, respectively; and (iii) vestibular compensation may involve regulation of both non-N-methyl-D-aspartate and N-methyl-D-aspartate receptors in the vestibular nuclear complex and activation of non-N-methyl-D-aspartate receptor-related processes in cerebellar cortex.

Immunolocalization of muscarinic acetylcholine subtype 2 receptors in rat cochlear nucleus.

It has been suggested that cholinergic effects in the rat cochlear nucleus (CN) are mediated by muscarinic acetylcholine receptors. In this study, immunohistochemistry for muscarinic subtype 2 (m2) receptors using a monoclonal subtype-specific antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356) revealed an m2-like system in the rat CN. A prominent lamina of m2-immunoreactive fibers and puncta was located in a subgranular layer of the caudal anteroventral cochlear nucleus (AVCN) and the posteroventral cochlear nucleus (PVCN). The superficial granular layer of the rostral AVCN and the medial sheet region also contained notable immunoreactivity for m2. Some labeled somata and their processes were found in magnocellular regions of the ventral CN. A network of neurites and puncta was located in the fusiform soma and deep layers of the dorsal CN. The olivocochlear bundle and its branches to the CN were also m2 immunoreactive and possibly contributed m2-labeled fibers and terminals to the CN. Some similarities and some differences were found between this m2 receptor distribution pattern and previous results for choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and muscarinic acetylcholine receptor immunohistochemistry and binding in the CN. The results suggest that m2 receptors that are located both pre- and postsynaptically mediate many cholinergic effects in the rat CN.