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PubMed2006

Projections of the second cervical dorsal root ganglion to the cochlear nucleus in rats.

Physiological, anatomical, and clinical data have demonstrated interactions between somatosensory and auditory brainstem structures. Spinal nerve projections influence auditory responses, although the nature of the pathway(s) is not known. To address this issue, we injected biotinylated dextran amine into the cochlear nucleus or dorsal root ganglion (DRG) at the second cervical segment (C2). Cochlear nucleus injections retrogradely labeled small ganglion cells in C2 DRG. C2 DRG injections produced anterograde labeling in the external cuneate nucleus, cuneate nucleus, nucleus X, central cervical nucleus, dorsal horn of upper cervical spinal segments, and cochlear nucleus. The terminal field in the cochlear nucleus was concentrated in the subpeduncular corner and lamina of the granule cell domain, where endings of various size and shapes appeared. Examination under an electron microscope revealed that the C2 DRG terminals contained numerous round synaptic vesicles and formed asymmetric synapses, implying depolarizing influences on the target cell. Labeled endings synapsed with the stalk of the primary dendrite of unipolar brush cells, distal dendrites of presumptive granule cells, and endings containing pleomorphic synaptic vesicles. These primary somatosensory projections contribute to circuits that are hypothesized to mediate integrative functions of hearing.

Acoustic Stimulation↗
PubMed1990

Contribution of centrifugal innervation to choline acetyltransferase activity in the cat cochlear nucleus.

Using a quantitative microchemical mapping approach combined with surgical cuts of fiber tracts, the contributions of centrifugal pathways to choline acetyltransferase activity were mapped three-dimensionally in the cat cochlear nucleus. Large reductions of choline acetyltransferase activity, averaging 70%, were measured in almost all parts of the lesion-side nucleus following transection of virtually all its centrifugal connections. More superficial cuts, penetrating just through the olivocochlear bundle, also led to significant reductions of enzyme activity, especially most rostrally in the anteroventral cochlear nucleus and superficial granular region, where the reductions were similar to those following the complete cuts. Lesions encroaching upon the superior olivary complex gave bilateral effects. Transverse cuts between rostral and caudal parts of the cochlear nucleus gave some small effects. The results suggest that, as in rats, most choline acetyltransferase activity in the cat cochlear nucleus is associated with its centrifugal innervation. However, unlike the situation in rats, the enzyme activity in cats is related more to olivocochlear branches than to ventral fibers in the trapezoid body region. Also, the choline acetyltransferase activity related to olivocochlear collateral innervation is much less uniformly distributed within the cochlear nucleus in cats than in rats.

Animals↗
PubMed2005

Amino acid concentrations in chinchilla cochlear nucleus at different times after carboplatin treatment.

Amino acid concentrations were measured in the cochlear nucleus for a group of 20 chinchillas: four each of control and 4, 8, 29, and 85 days after treatment with the ototoxic anti-tumor drug carboplatin (100 mg/kg, i.p.). The treated chinchillas showed various extents of inner hair cell loss, generally more complete at longer survival times, but little loss of outer hair cells. Aspartate concentration in rostral anteroventral cochlear nucleus (AVCN) showed a decline to 28% less than the control value at 29 and 85 days after treatment, whereas glutamate concentration showed little change through 29 days, then dropped by 22% at 85 days after treatment. In caudal posteroventral cochlear nucleus (PVCN), the aspartate concentration decreased by 32% at 29 days, in animals with significant inner hair cell loss, and 48% at 85 days after treatment, while the glutamate concentration showed no decrease through 29 days and 40% decrease at 85 days. The concentration of gamma-aminobutyrate (GABA) was about 18% lower than control in caudal PVCN at all survival times. Significant correlations were found between the proportion of inner hair cells remaining and glutamate and aspartate concentrations in PVCN and AVCN, but not GABA or other amino acids.

Amino Acids↗
PubMed1991

Auditory projections from the cochlear nucleus to pontine and mesencephalic reticular nuclei in the rat.

We investigated projections from the cochlear nucleus in the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. We focused on nuclei in the brainstem which are not considered to be part of the classical auditory pathway. In addition to labeling in auditory nuclei, we found presumed terminal fibers in 4 pontine and mesencephalic areas: (1) the pontine nucleus (PN), which receives bilateral projections from the antero- and posteroventral cochlear nuclei; (2) the ventrolateral tegmental nucleus (VLTg), which receives a contralateral projection from the rostral portion of the anteroventral cochlear nucleus; (3) the caudal pontine reticular nucleus (PnC), which receives bilateral input originating predominantly in the dorsal cochlear nucleus; and (4) the lateral paragigantocellular nucleus (LPGi), which receives projections from all subdivisions of the cochlear nuclei. In the VLTg and PnC, anterogradely labeled varicose axons were often found in close apposition to the primary dendrites and somata of large reticular neurons. Injections of the retrograde fluorescent tracer Fluoro-Gold into the VLTg demonstrated that the neurons of origin are mainly located contralaterally in the rostral anteroventral cochlear nucleus and in the cochlear root nucleus. The relevance of these auditory projections for short-latency audio-motor behaviors and acoustically elicited autonomic responses is discussed.

Animals↗
PubMed1983

Age-dependent effects of acoustic deprivation on spherical cells of the rat anteroventral cochlear nucleus.

The effects of monaural deprivation by ligation of the external auditory meatus on spherical cells in the anteroventral cochlear nucleus of the rat were examined. Sound deprivation from postnatal days 10, 16, 24, and 36 resulted in a reduction in spherical cell size, with the most dramatic reduction produced by deprivation at 10 and 16 days after birth. The anteroventral cochlear nucleus was subdivided into dorsal, middle, and ventral zones which generally correspond to different frequency representations, and the effects of deprivation on cells in these regions were examined. Cells in the dorsal zone of the anteroventral cochlear nucleus were significantly smaller than cells in the middle or ventral zones, thus indicating a position-dependent effect of acoustic deprivation. Our results suggest a sensitive period during which alterations in normal acoustic input can significantly and differentially affect the development of cells in the anteroventral cochlear nucleus.

Age Factors↗
PubMed1998

Long-term degeneration in the cochlear nerve and cochlear nucleus of the adult chinchilla following acoustic overstimulation.

Adult chinchillas were exposed once to an octave-band noise, centered at 4 kHz, and allowed to survive for 16 days or for 1, 2, 4, and 8 months. Axonal degeneration was mapped in the cochlear nucleus, using the Nauta-Rasmussen silver method, and related to hair cell damage and to loss of myelinated nerve fibers in the osseous spiral lamina of the cochlea. Axonal degeneration in the dorsal cochlear nucleus had already reached a peak by 16 days and disappeared after 1 month. Meanwhile, myelinated nerve fiber degeneration in the cochlea extended basally, followed 2 weeks to 2 months later by spread of axonal degeneration into the corresponding high-frequency region of the ventral cochlear nucleus. Axonal degeneration occurred early in the low-frequency region of the ventral cochlear nucleus, followed 2-4 weeks later by spread of myelinated fiber degeneration into more apical regions of the cochlea. New degeneration of axons in the cochlear nerve and in the ventral cochlear nucleus continued to occur for up to 8 months after stimulation. These findings imply that plastic changes in the central auditory pathways could play a role in the long-term effects of cochlear damage and acoustic overstimulation, possibly leading to a chronic neurodegenerative condition in the ear and in the brain.

Acoustic Stimulation↗
PubMed2002

Aminergic projections to cochlear nucleus via descending auditory pathways.

The cochlear nucleus (CN) receives descending input from a variety of auditory nuclei. Descending inputs from the superior olive in particular have been well described, especially those of olivocochlear neurons, which terminate ultimately in the cochlea. It has been demonstrated that olivocochlear neurons receive serotonergic and noradrenergic inputs and thus form a route by which the aminergic system may modulate cochlear mechanisms. Since olivocochlear neurons send collaterals into the CN, it is possible that they also from a route by which the aminergic systems modulate CN processes. The goal of the current study was to determine if neurons in the superior olive that projected to the CN received serotonergic or noradrenergic inputs. The retrograde tracer WGAapoHRP-Au was injected into the CN of cats. The brainstems were silver-enhanced to visualize the tracer and then immunohistochemically processed with antibodies raised against serotonin or dopamine-beta-hydroxylase (DBH) to label serotonergic or noradrenergic fibers, respectively. The sections were viewed with high power light microscopy to determine if the retrogradely labeled neurons were contacted by serotonin- or DBH-immunoreactive varicosities. Retrogradely labeled cells were observed in auditory brainstem nuclei known to project to the CN including the superior olivary complex and inferior colliculus bilaterally and the opposite CN. In these regions, retrogradely labeled neurons were closely associated with serotonin- and/or DBH-immunoreactive varicosities. Assuming a synaptic relationship between the projection neurons and varicosities, these results indicate that the serotonergic and noradrenergic systems innervate the descending pathways to the CN. Since the serotonergic and noradrenergic systems modulate their targets based on level of arousal, these results support the theory that descending systems are involved in selective attention.

Animals↗
PubMed1988

Projection of primary vestibular afferent fibres to the cochlear nucleus in the guinea pig.

After tracing the superior branch of the vestibular nerve and the macula sacculi by means of the neuronal tracers horseradish peroxidase (HRP) and wheat germ conjugated horseradish peroxidase (WGA-HRP), a conspicuous fibre bundle running into the cochlear nucleus could be observed. The HRP-labeled axons travel caudally through the descending vestibular nucleus, enter the cochlear nucleus at a level caudal to subgroup y and terminate at cells situated between the dorsal and posteroventral cochlear nucleus. Considering recent electrophysiological studies, it is reasonable to imply that these fibres are involved with the transduction of acoustic stimuli.

Afferent Pathways↗
PubMed1991

Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups.

Mechanisms underlying bilirubin encephalopathy and hearing loss remain poorly understood, including the way bilirubin enters the nervous system and how bilirubin accumulates in circumscribed regions of the brain. The present experiments examined the auditory brainstem in heterozygous (Nj) and homozygous (jj) Gunn rats at an age when serum bilirubin levels were highest, and after brain bilirubin concentration was artificially raised by sulfadimethoxine administration. In four litters of 11-12 days old Gunn rats, Nj and jj littermates received a single intraperitoneal injection of sulfadimethoxine (100 mg/kg) or a comparable volume of saline. At 16-17 days of age, brainstem auditory evoked potentials were recorded to assess the severity of bilirubin toxicity in the Nj and jj animals. Following the recordings, each animal was perfusion-fixed and frozen sections of the brainstem were cut in the transverse plane from medullary through mesencephalic levels. Sections were mounted on slides, stained with thionin and coded to avoid observer bias. Quantitative analysis revealed no differences between saline and sulfa-treated Nj rats for cochlear nucleus volume, or for cell size in the cochlear nucleus or superior olive. In the sulfa-treated jj rats, cochlear nucleus volume, and cross-sectional areas of spherical cells in the anteroventral cochlear nucleus and principal cells in the nucleus of the trapezoid body, were all significantly smaller than in the combined groups of Nj animals. The affected areas in the cochlear nucleus and superior olive are innervated by large axosomatic end-bulbs of Held or calyceal endings, and were associated with bilirubin staining of glia in the most severely jaundiced jj sulfa-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

[Contribution of cochlear nucleus to 80Hz amplitude-modulation following response].

The steady-state response (SSR) evoked by a sinusoidally amplitude-modulated (SAM) tone is known as an amplitude-modulation following response (AMFR). The amplitude of the SSR which is elicited using clicks or tone bursts at a stimulus rate of 40 Hz, decreases during sleep. The same trend is also observed for AMFR at a modulation rate of 40 Hz. Thus it was difficult to analyzing SSR and AMFR is therefore difficult in young children, since objective audiometry just be performed while the child is asleep. Recent reports, however, have announced that the AMFR can be clearly detected at higher MFs (modulation frequencies), especially at frequencies between 80 and 100 Hz. This finding has proven useful in objective audiometry for young children. Recent reports have also suggested that AMFRs arise from multiple sources, including the auditory cortex and auditory nuclei in the brainstem. However, the exact sources of AMFRs have not been clarified. The purpose of this study is to clarify the contribution of the cochlear nucleus in evoking AMFRs at a modulation frequency of 80 Hz. The near-field potentials elicited with a SAM tone were recorded from the ipsilateral cochlear nucleus and its vicinity in cats. The near-field potential recorded by bipolar electrodes consisted of two different components: a low frequency component similar to the stimulus envelope (modulation), and a high frequency component similar to the actual stimulus tone. A sequence of field potentials was recorded using monopolar electrodes located at different sites within the cochlear nucleus and in its vicinity and on the surface of the cerebellum to confirm that near-field potentials elicited by SAM tones at a MF of 80 Hz in the cochlear nucleus can be recorded at the surface of the cerebellum or at other brain sites. The phase of the 80 Hz frequency component of the potentials elicited by a SAM tone at a MF of 80 Hz was then analyzed using a fast Fourier transformation. A contour map was produced using the means of the Fourier component phases corresponding to the 80 Hz response. The contour lines showed a rapid change in the phases recorded near the cochlear nucleus. These findings suggest that the cochlear nucleus contributes to the generation of scalp recorded AMFR at a MF of 80 Hz.

Acoustic Stimulation↗
PubMed1999

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.

Amino Acids↗
PubMed1994

Changing patterns of peanut agglutinin labelling in the dorsal cochlear nucleus correspond to axonal ingrowth.

Various studies have suggested that glycoconjugates may influence connectivity and lamination in the developing central nervous system and may function as barriers to neuritic extension. It has been proposed that the peanut agglutinin lectin labels a glycoconjugate subserving a barrier function. We chose to investigate the distribution of this peanut-agglutinin-labelled glycoconjugate in the dorsal cochlear nucleus of the developing hamster since the development of the dorsal cochlear nucleus is well characterised and its axons obey laminar boundaries. The distribution of peanut agglutinin label throughout the cochlear nucleus delineated zones that cochlear axons fail to invade. In the dorsal cochlear nucleus, laminar differences were reduced on postnatal d 13 and virtually disappearing by postnatal d 23. Label in the molecular layer dissipated as axons and dendrites grew into this layer. These patterns of peanut agglutinin binding correspond to axonal ingrowth and are consistent with a barrier function for glycoconjugates in the molecular layer.

Animals↗
PubMedDate not supplied

Age-dependent effects of the onset of a conductive hearing loss on the volume of the cochlear nucleus subdivisions and the expression of c-fos in the mongolian gerbil (Meriones unguiculatus).

A monaural conductive hearing loss was induced by interrupting the chain of the middle ear ossicles on the right side in gerbils of four different age groups (P12-14, P20-21, P42 and P84). The volumes of the cochlear nucleus subdivisions and the number of cells that expressed immunoreactivity for c-fos after noise stimulation were determined on the left and right side in the deprived animals, and in undeprived control animals when they reached the age of 6 months. The anteroventral cochlear nucleus on the deprived side was reduced in volume when the deprivation started before the age of 3 months. The other cochlear nucleus subdivisions showed no systematic age-dependent reductions. The expression of c-fos in the dorsal cochlear nucleus appeared more resistant to a hearing loss, with deprivation being more effective in younger animals. c-fos expression was also dramatically reduced in the ventral cochlear nucleus, regardless of age at the onset of hearing loss.

Acoustic Stimulation↗
PubMed2005

Presence and distribution of three calcium binding proteins in projection neurons of the adult rat cochlear nucleus.

The presence and distribution of three cytoplasmic calcium binding proteins, calbindin, calretinin, and parvalbumin, have been investigated in the projection neurons of the cochlear nucleus complex in adult rats by using immunohistochemistry in free-floating slices. Identification of the individual cell types was carried out on the basis of their intranuclear localization, morphological characteristics, and (in the cases of pyramidal and bushy neurons) by retrograde labeling with rhodamine-dextran. The most important findings were confirmed by using confocal microscopy. The data obtained in these experiments are the first to demonstrate the presence of parvalbumin in pyramidal neurons and globular and spherical bushy cells of rat cochlear nucleus, whereas octopus and giant cells did not show positivity for parvalbumin. Calretinin was not present in either Purkinje-like cells or giant neurons. According to the double immunolabeling co-localization experiments, the pyramidal neurons, Purkinje-like cells, globular bushy cells, and octopus cells express two different calcium binding proteins in their cytoplasm (although in different combinations) whereas giant cells and spherical bushy cells contain solely calbindin and parvalbumin, respectively. The presence of calretinin in globular bushy cells provides a tool for distinguishing them from spherical bushy cells. The immunolabeling of the fibers and axonal endings of the acoustic nerve in the ventral part of the cochlear nucleus indicated that these structures are also parvalbumin positive. It is concluded that the heterogenous cell composition of the cochlear nucleus is accompanied by a rather complex expression pattern of the cytoplasmic calcium binding proteins.

Animals↗
PubMed2002

5-HT(1A) receptor subtype mRNA expression in cochlear nucleus.

Previous studies indicate expression of various serotonin receptor subtypes, including the 5-HT(1A) receptor subtype, in rodent cochlear nucleus. Our long-term goal is to identify the types of cochlear nucleus neurons, which are well described in cat, that express 5-HT receptors. In the current study, the reverse transcriptase/polymerase chain reaction and the in situ hybridization method were used to detect the mRNA encoding a portion of the 5-HT(1A) receptor subtype in the cochlear nucleus of the cat.

Animals↗
PubMed2005

Voltage-gated and background K+ channel subunits expressed by the bushy cells of the rat cochlear nucleus.

Bushy cells of the ventral cochlear nucleus produce a single, short latency action potential at the beginning of long depolarisations. In the present work an immunochemical survey was performed to detect the presence of K+ channel subunits which may contribute to the specific membrane properties of the bushy cells. The immunocytochemical experiments conducted on enzymatically isolated bushy cells indicated positive immunolabelling for several subunits known to be responsible for the genesis of rapidly inactivating K+ currents. Bushy cells showed strong expression of Kv3.4, 4.2 and 4.3 subunits, with the lack of Kv1.4 specific immunoreaction. The Kv3.4-specific immunoreaction had a specific, patchy appearance. Bushy cells also expressed various members of the Kv1 subunit family, most notably Kv1.1, 1.2, 1.3 and 1.6. Weak positivity could be observed for Kv3.2 subunits. The positive immunolabelling for Kv3.4, Kv4.2 and Kv4.3 was confirmed in free-floating tissue slices. Voltage-clamp experiments performed on positively identified bushy cells in brain slices corroborated the presence and activity of Kv3.4 and Kv4.2/4.3 containing K+ channels. Bushy cell showed strong immunopositivity for TASK-1 channels too. The results presented in this work indicate that bushy cells possess several types of voltage-gated K+ channel subunits whose activity may contribute to the membrane properties and firing characteristics of these neurones.

Animals↗
PubMed2003

Kinetic analyses of three distinct potassium conductances in ventral cochlear nucleus neurons.

Neurons in the ventral cochlear nucleus (VCN) express three distinct K+ currents that differ in their voltage and time dependence, and in their inactivation behavior. In the present study, we quantitatively analyze the voltage-dependent kinetics of these three currents to gain further insight into how they regulate the discharge patterns of VCN neurons and to provide supporting data for the identification of their channel components. We find the transient A-type K+ current (IA) exhibits fourth-order activation kinetics (a4), and inactivates with one or two time constants. A second inactivation rate (leading to an a4bc kinetic description) is required to explain its recovery from inactivation. The dendrotoxin-sensitive low-threshold K+ current (ILT) also activates with fourth-order kinetics (w4) but shows slower, incomplete inactivation. The high-threshold K+ current (IHT) appears to consist of two kinetically distinct components (n2 + p). The first component activates approximately 10 mV positive to the second and has second-order kinetics. The second component activates with first-order kinetics. These two components also contribute to two kinetically distinct currents upon deactivation. The kinetic behavior of IHT was indistinguishable amongst cell types, suggesting the current is mediated by the same K+ channels amongst VCN neurons. Together these results provide a basis for more realistic modeling of VCN neurons, and provide clues regarding the molecular basis of the three K+ currents.

Animals↗
PubMed2000

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus.

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells-chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.

Acoustic Stimulation↗