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PubMed2002

Synaptophysin in the cochlear nucleus following acoustic trauma.

Chinchillas are notable for a low-frequency hearing range similar to that of humans and a marked sensitivity to loud noise. A single noise exposure that produces cochlear damage may lead to progressive loss of synaptic endings in the cochlear nucleus, followed by new axonal growth. As an index of synaptic regulation during such changes, we have examined the expression of a synaptic vesicle protein, synaptophysin, in the cochlear nucleus following a damaging acoustic stimulus in adult chinchillas. With one ear protected by a plug, following a 3-h exposure to an octave-band noise of 108 dB sound pressure level, centered at 4 kHz, the unprotected cochlea and the cochlear nuclei exhibited degeneration of hair cells and axons over periods of 7, 14, 30, 90, and 150 days. Axonal degeneration, as revealed by a silver degeneration method, was heavy ipsilateral to the cochlear damage, but sparse degeneration also appeared on the contralateral, unexposed side. Synaptophysin immunostaining underwent a major, bilateral decline in the anteroventral and posteroventral cochlear nuclei, interrupted at intervening periods by transient increases in the numbers of stained structures. A distinction in staining between large perisomatic structures and smaller puncta in the neuropil and between the dorsal and the ventral zones of the ventral cochlear nuclei revealed some variations in the response and degree of recovery of synaptophysin staining. These findings could best be explained by degeneration of synaptic endings followed by new growth of terminals and by regulatory changes in the levels of synaptophysin expression and synaptic vesicle accumulation over time.

Acoustic Stimulation↗
PubMed2002

Morphological evidence for secondary vestibular afferent connections to the dorsal cochlear nucleus in the rabbit.

An analysis of central afferent projections to the dorsal cochlear nucleus (dCo), one of the three target nuclei of the auditory nerve, was made using retrograde axonal tracer, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the rabbit. The findings showed that, in addition to its afferents from the brainstem auditory nuclei (they are not described herein), the dCo received sparse bilateral connections from the caudal three quarters of the vestibular nuclear complex (VNC). Following selective iontophoretic injections of WGA-HRP into the dCo, a small number of labelled neurones (from 2 to 28 per case) was found in the rostral and caudal portions of the medial vestibular nucleus and in the inferior vestibular nucleus. These neurones were observed mainly in the lateral regions of the nuclei. No labelling appeared in other nuclei which belonged to the VNC. The secondary vestibulocochlear connections have not been reported before in any species. With the anatomical method used, however, their functional role is difficult to explain. Further study is necessary to identify the type of neurotransmitter as well as the physiological properties of vestibular neurones projecting to the dCo, in terms of their responses to a change of the head position and to sound.

Afferent Pathways↗
PubMed1997

Naturally occurring neuron death during postnatal development of the gerbil ventral cochlear nucleus begins at the onset of hearing.

Postnatal development of the gerbil ventral cochlear nucleus (VCN) was studied quantitatively under the light microscope in Nissl-stained serial sections at postnatal day 0 (P0), P5, P7, P10, P12, P15, and P140. VCN boundaries were unambiguous at all ages, and nucleus volume was calculated planimetrically for all groups. Measurements of neuron soma cross-sectional area and number were made in all groups except P0. Both VCN volume and soma area doubled between P5 and P10. Although somatic growth did not continue beyond P10, VCN volume increased a further 57% between P15 and P140. Neuron number did not change significantly between P5 and P10, averaging approximately 36,000 neurons. Between P10 and P12, neuron number decreased significantly by 22%, with no further change thereafter. Our data show that, following significant postnatal growth in the gerbil VCN, a brief period of naturally occurring neuron death begins at the onset of hearing.

Aging↗
PubMed1984

Unit responses at cochlear nucleus to electrical stimulation through a cochlear prosthesis.

Afferent auditory fibers of the guinea pig cochlea were electrically stimulated with current introduced through electrodes in the scala tympani. Thresholds were determined for unit responses recorded in the ventral cochlear nuclei to a sinusoid of 98 Hz from response-rate growth functions versus stimulus intensity. Suprathreshold response rates for most units grew rapidly from threshold to saturation at 2-15 dB above threshold. Peristimulus time histograms were collected for responses to single sinusoids and combinations of two and five sinusoids ranging from 86 to 134 Hz. Spike occurrences were highly synchronous with individual cycles of the pure sinusoids, but responses to the more complex waveforms occurred primarily to the more intense peaks. The amplitude envelope was thus a major contributor to responses to multiple sinusoids. Destruction of cochlear structures with neomycin increased unit thresholds and produced some changes in waveform encoding.

Action Potentials↗
PubMed1984

Single unit responses in the cochlear nucleus of the deaf quivering mouse.

Mice homozygous for the autosomal recessive gene quivering do not have a classical Preyer reflex and appear to be deaf. Round window recordings including both cochlear microphonics and compound action potentials failed to reveal any abnormality. However, auditory-evoked potentials recorded from the inferior colliculus (IC) are small with long latencies, and the thresholds are at least 50 dB higher than those recorded in controls. This suggests that the auditory deficit arises in the auditory pathway between the cochlear nerve and IC and underlines the need for a description of the functioning of the cochlear nucleus (CN). Single units were recorded extracellularly from the CN in 9 mutants (qv/qv) and 11 control animals (+/qv, or +/+) in the age range 60-120 days. The spike response pattern in mutant animals was broadly similar to that in the controls: a sustained response with monotonic rate-intensity functions. In addition the mean Q10dB for units in the mutants was similar to that of the controls. However, in mutants the group mean threshold at the characteristic frequency was higher and the latency to the first evoked spike at 20 dB above threshold was longer than in controls. Some unit responses in the mutants were similar to those of the controls. Nevertheless, in the quivering mouse, evidence now exists of single unit dysfunction in the cochlear nucleus.

Acoustic Stimulation↗
PubMed1991

Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig.

This investigation attempted to determine the mode of distribution and synaptic targets of the cartwheel cell axon in the guinea pig dorsal cochlear nucleus (DCoN). Antiserum against PEP-19, a putative calcium-binding neuropeptide, was employed at the light and electron microscopic levels. We show that in the hind-brain of the guinea pig, cerebellar Purkinje cells and DCoN cartwheel cells are the most densely immunoreactive neurons. The PEP-19 immunoreaction product is localized to all neuronal compartments of these cells. Primary targets of cartwheel cell axons are the DCoN pyramidal cells, the large efferent neurons of layer 2. These neurons receive numerous immunoreactive synaptic boutons on their cell bodies and apical and basal dendritic arbors. A PEP-19-immunoreactive axonal plexus, largely formed by cartwheel cell axons, highlights layer 3, co-extensively with the basal arbors of pyramidal cells. This plexus is oriented predominantly in the transstrial plane of the DCoN, in parallel with the sheet-like basal dendritic arbor of pyramidal neurons and with the isofrequency bands of primary cochlear nerve fibers. PEP-19-positive boutons contain pleomorphic synaptic vesicles and form symmetric synaptic junctions, indicative of inhibitory innervation. In addition, immunoreactive boutons, similar to those synapsing on pyramidal neurons, were observed on the cell bodies and main dendritic trunks of cartwheel neurons, indicating a system of recurrent collaterals. Furthermore, a small number of PEP-19-positive axons of unknown origin reach the caudal rim of the posteroventral cochlear nucleus. Within the territory of distribution of the cartwheel cell axon are the dendrites of at least two other types of DCoN neuron, the vertical cells of Lorente de Nó and the giant cells. These neurons may represent additional targets of the cartwheel cell axon, but this remains to be ascertained with specific methods. Our data demonstrate that the cartwheel neurons modulate the activity of pyramidal neurons and, therefore, play a key role in shaping the output of the DCoN superficial layers.

Animals↗
PubMed2001

Physiological correlates of comodulation masking release in the mammalian ventral cochlear nucleus.

Comodulation masking release (CMR) enhances the detection of signals embedded in wideband, amplitude-modulated maskers. At least part of the CMR is attributable to across-frequency processing, however, the relative contribution of different stages in the auditory system to across-frequency processing is unknown. We have measured the responses of single units from one of the earliest stages in the ascending auditory pathway, the ventral cochlear nucleus, where across frequency processing may take place. A sinusoidally amplitude-modulated tone at the best frequency of each unit was used as a masker. A pure tone signal was added in the dips of the masker modulation (reference condition). Flanking components (FCs) were then added at frequencies remote from the unit best frequency. The FCs were pure tones amplitude modulated either in phase (comodulated) or out of phase (codeviant) with the on-frequency component. Psychophysically, this CMR paradigm reduces within-channel cues while producing an advantage of approximately 10 dB for the comodulated condition in comparison with the reference condition. Some of the recorded units showed responses consistent with perceptual CMR. The addition of the comodulated FCs produced a strong reduction in the response to the masker modulation, making the signal more salient in the poststimulus time histograms. A decision statistic based on d' showed that threshold was reached at lower signal levels for the comodulated condition than for reference or codeviant conditions. The neurons that exhibited such a behavior were mainly transient chopper or primary-like units. The results obtained from a subpopulation of transient chopper units are consistent with a possible circuit in the cochlear nucleus consisting of a wideband inhibitor contacting a narrowband cell. A computational model was used to confirm the feasibility of such a circuit.

Acoustic Stimulation↗
PubMed2002

Intracellularly labeled fusiform cells in dorsal cochlear nucleus of the gerbil. I. Physiological response properties.

Fusiform cells in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized Mongolian gerbils were characterized physiologically and labeled with neurobiotin. This report is based on 17 fusiform cells for which there was reasonable confidence in the association between physiological data and recovered anatomy. The qualitative morphology of these cells was no different from that reported in previous studies. The acoustic response properties were generally consistent with those described in the barbiturate-anesthetized cat. Most responses were of the pauser or buildup type, but a dependence on stimulus frequency and intensity was observed. Stimulus-evoked sustained depolarizations and large, long-lasting afterhyperpolarizations were common membrane potential features. The cells in this study showed a greater tendency to discharge regularly than did those of the cat, likely as a result of the longer interstimulus interval used. Barbiturate anesthesia appears to mask an interspecies difference in DCN physiology that is apparent in unanesthetized, decerebrate preparations. The response of these fusiform cells to a depolarizing current pulse could be altered by the presence of a hyperpolarizing prepulse. Buildup, pauser, and chopper patterns could each be created using appropriate combinations of hyperpolarizing and depolarizing pulse amplitudes. Thus the adult gerbil appears to express the inactivating potassium conductance previously shown to affect fusiform cell firing patterns in vitro. The results further demonstrate that the effects of these potassium currents are readily observed in vivo. Finally, the fusiform cells in this study were quite variable with respect to a number of response properties, including the resting potential, input resistance, spontaneous activity, relative noise index, normalized tone slope, and regularity histogram shape. This diversity likely results from cell-to-cell variations in the balance of activity within the relatively complex network to which the fusiform cells belong, although effects of impalement may contribute to the extent of the diversity.

Acoustic Stimulation↗
PubMed1996

Ultrastructural study of the granule cell domain of the cochlear nucleus in rats: mossy fiber endings and their targets.

The principal projection neurons of the cochlear nucleus receive the bulk of their input from the auditory nerve. These projection neurons reside in the core of the nucleus and are surrounded by an external shell, which is called the granule cell domain. Interneurons of the cochlear granule cell domain are the target for nonprimary auditory inputs, including projections from the superior olivary complex, inferior colliculus, and auditory cortex. The granule cell domain also receives projections from the cuneate and trigeminal nuclei, which are first-order nuclei of the somatosensory system. The cellular targets of the nonprimary projections are mostly unknown due to a lack of information regarding postsynaptic profiles in the granule cell areas. In the present paper, we examined the synaptic relationships between a heterogeneous class of large synaptic terminals called mossy fibers and their targets within subdivisions of the granule cell domain known as the lamina and superficial layer. By using light and electron microscopic methods in these subdivisions, we provide evidence for three different neuron classes that receive input from the mossy fibers: granule cells, unipolar brush cells, and a previously undescribed class called chestnut cells. The distinct synaptic relations between mossy fibers and members of each neuron class further imply fundamentally separate roles for processing acoustic signals.

Animals↗
PubMed1985

GABA neurons in the superficial layers of the rat dorsal cochlear nucleus: light and electron microscopic immunocytochemistry.

This article is an application of light and electron microscopic immunocytochemistry to the study of the neuronal circuit of the superficial layers in the rat dorsal cochlear nucleus (DCN). An antiserum against the intrinsic marker glutamate decarboxylase (GAD) is used to identify and map axon terminals and neurons that use gamma aminobutyric acid (GABA) as a neurotransmitter. It is demonstrated that layers 1 and 2 of the DCN contain a very high density of GABAergic boutons, matched only by the granule cell domains of the ventral cochlear nucleus, especially the superficial granule cell domain. These two layers also contain much higher concentrations of GABAergic cell bodies than all other magnocellular regions of the cochlear nuclear complex. Cartwheel and stellate neurons, and probably also Golgi cells, previously characterized in Golgi and electron microscopic investigations, appear immunostained and, therefore, are presumably inhibitory. The synaptic relations between parallel fibers, the axons of granule cells, and cartwheel and stellate neurons are confirmed. The present study also supports the conclusion that stellate cells are coupled to one another by gap junctions. Also scattered in layer 1 are large, GABAergic neurons that occur with irregular frequency and presumably represent displaced Purkinje cells, previously identified with a Purkinje-cell-specific marker. Granule neurons and pyramidal neurons remain unstained, even after topical injection of colchicine, which enhances immunostaining of the other glutamate-decarboxylase-positive cells, and therefore must use transmitters different from GABA. The possible analogies between the spiny cartwheel and the aspiny stellate cells of the DCN and the cerebellar Purkinje and stellate/basket cells are discussed in the light of data from Golgi, electron microscopy, and transmitter imunocytochemistry.

Animals↗
PubMed2006

Safety study of the Cochlear Nucleus 24 device with internal magnet in the 1.5 Tesla magnetic resonance imaging scanner.

OBJECTIVES: To evaluate the effect of the 1.5 Tesla magnetic resonance imager (MRI) on the Cochlear Nucleus 24 Device without removing the internal magnet. To determine whether device fixation using a compression dressing could prevent internal magnet displacement in the MRI scanner and potentially obviate the need for surgical removal of the internal magnet. STUDY DESIGN: Prospective cadaveric study. METHODS: Four cadaver heads were implanted bilaterally with the Nucleus device with the internal magnet in place and placed into the 1.5 Tesla MRI scanner. The devices were then explanted after interaction with the MRI and evaluated for displacement of the internal magnet. Conditions tested include device fixation with a commercially available compression dressing and no fixation (worst-case scenario). Magnet strength was measured before and after each of the test conditions. RESULTS: Moderate to severe displacement of the magnet from the internal device occurred in 14 of 16 (87%) implants when no compression dressing was placed. Displacement occurred in 0 of 16 (0%) implants when the compression dressing was applied. No decrease in the strength of the implant magnet was found with the initial or subsequent MRI/implant interactions. CONCLUSIONS: Use of the 1.5 Tesla MRI on subjects with Cochlear Nucleus 24 implants did not result in any significant demagnetization of the internal magnet and did not cause displacement of the magnet when an external compression dressing was applied. Surgical removal of the internal magnet before scanning with the 1.5 Tesla MRI may not be necessary if a compression dressing is applied.

Cadaver↗
PubMed1993

Cartwheel and superficial stellate cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices.

1. Intracellular recordings were made from identified cartwheel and stellate cells in the molecular and fusiform cell layers of the murine dorsal cochlear nucleus (DCN). The aim of the study was to identify and characterize their synaptic inputs and to learn how synaptic inputs and intrinsic electrical properties interact to generate firing patterns. 2. Eight cells labeled by the intracellular injection of biocytin were cartwheel cells. Their axon terminals extended from the deep part of the molecular layer through the fusiform cell layer. Their dendrites extended through the molecular layer and had spines. Both the dendritic and axonal arbors were small, having diameters of approximately 150 microns in the parasagittal plane. 3. When depolarized, cartwheel cells often fired bursts of rapid action potentials superimposed on a slow depolarization. The peaks of action potentials were usually overshooting. Individually occurring action potentials were followed by two afterhyperpolarizations, as in other cells of the DCN. During bursts, action potentials did not have two distinct repolarizing phases. 4. Excitatory postsynaptic potentials (EPSPs) were recorded from cartwheel cells spontaneously and after shocks to the nerve root or to the ventral cochlear nucleus (VCN). The EPSPs rose slowly. When they were suprathreshold they evoked action potentials singly or in bursts. EPSPs evoked by shocks to the nerve root or to the VCN had long latencies, the rise of EPSPs beginning between 5 and 10 ms after the shock. No inhibitory synaptic potentials, either spontaneous or driven with electrical stimulation, were detected in cells whose resting potentials were between -50 and -70 mV. 5. The locations from which excitatory input can be driven electrically are consistent with cartwheel cells receiving excitatory synaptic input from granule cells. 6. One labeled cell was a superficial stellate cell. It had smooth, straight dendrites that radiated parallel to the layers of the DCN; its axonal arbor was also planar and was restricted to the molecular layer. Both the dendritic and axonal arbors of this stellate cell were large, > 500 microns diam in the parasagittal plane. 7. The superficial stellate cell fired trains of action potentials at regular intervals that, like other cells of the DCN, were overshooting and were followed by double undershoots. 8. Shocks to the nerve root and to the surface of the VCN evoked EPSPs after 3.5 and 2 ms, respectively, in the superficial stellate cell. Chemical stimulation of the VCN also evoked excitation. No inhibitory synaptic input, spontaneous or driven, was detected.

Animals↗
PubMed1997

Cochlear nucleus cell size changes in the dalmatian: model of congenital deafness.

We assessed cellular changes in one population of neurons of the cochlear nucleus associated with a form of genetic deafness in deaf dalmatians. Spheric cells from deaf dalmatians and age-matched control (hearing) dogs were analyzed morphometrically. The somatic silhouette of these cells was reduced by 22.1% to 38.1%. The effect on cell size was greater with increased duration of deafness. Because the deaf dalmatian exhibits progressive degeneration of the auditory periphery, shrinkage of spheric cells may reflect the initial influence of attenuated activity of auditory nerve fibers, and sensorineural degeneration with longer periods of deafness.

Age Factors↗
PubMed1975

A block model of the cat cochlear nucleus.

A three-dimensional block model of the cochlear nucleus of the cat was constructed from histologic sections. Boundaries of various subdivisions, based on cytoarchitectonic criteria, were included in the model. Usage of the block model in correlating physiological and anatomical data is illustrated by localizing characteristic waveforms of gross evoked responses and characteristic frequencies of single units.

Animals↗
PubMed1991

Structure and topography of the cochlear nucleus in bison.

Investigations were performed in 3 bisons of Białowieza herd. Brain stems were fixed in 10% formaldehyde and cut transversely in sections of 15 microns. Sections were stained with hematoxylin and luxol fast blue. The cochlear nucleus in bison is divided into ventral and dorsal cellular bands. The ventral nucleus is longer and it is subdivided into dorsal and ventral parts. It is formed by round and multipolar cells. The dorsal cochlear nucleus shows laminar structure. Within the nucleus the ependymal, molecular and polymorphic zones may be distinguished. The cells are round, fusiform and multipolar.

Animals↗
PubMed2001

Maturation of synaptic transmission at end-bulb synapses of the cochlear nucleus.

Neurons of the avian nucleus magnocellularis transmit phase-locked action potentials of the auditory nerve in a pathway that contributes to sound localization based on interaural timing differences. We studied developmental changes in synaptic transmission that enable the end-bulb synapse to function as a synaptic relay. In chick, although the auditory system begins to function early in embryonic development, maturation of audition around the time of hatching suggested that synaptic transmission in the cochlear nucleus of young chicks may undergo further developmental changes. Synaptic physiology was investigated via patch-clamp recordings from bushy cells in brainstem slices during stimulation of auditory nerve fibers at 35 degrees C. Compared with embryonic synapses (embryonic day 18), post-hatch chicks (post-hatch days 1-11) exhibited high probability of firing a well timed postsynaptic action potential during high-frequency stimulation of the auditory nerve. Improvements in reliability and timing of postsynaptic spikes were accompanied by a developmental increase in steady-state EPSCs during stimulus trains and a decline in the extent of synaptic depression. Synchrony of EPSCs during stimulus trains improved with age. An increased pool of synaptic vesicles, lower release probability, larger and faster transmitter quanta, and reduced AMPA receptor desensitization contributed to these changes. Together, these factors improve the ability of cochlear nucleus magnocellularis neurons to faithfully transmit timing information encoded by the auditory nerve.

Action Potentials↗
PubMedDate not supplied

Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis.

PURPOSE: Of all nonauditory sensory systems, only the somatosensory system seems to be related to tinnitus (eg, temporomandibular joint syndrome and whiplash). The purpose of this study is to describe the distinguishing characteristics of tinnitus associated with somatic events and to use these characteristics to develop a neurological model of somatic tinnitus. MATERIALS AND METHODS: Case series. RESULTS: Some patients with tinnitus, but no other hearing complaints, share several clinical features including (1) an associated somatic disorder of the head or upper neck, (2) localization of the tinnitus to the ear ipsilateral to the somatic disorder, (3) no vestibular complaints, and (4) no abnormalities on neurological examination. Pure tone and speech audiometry of the 2 ears is always symmetric and usually within normal limits. Based on these clinical features, it is proposed that somatic (craniocervical) tinnitus, like otic tinnitus, is caused by disinhibition of the ipsilateral dorsal cochlear nucleus. Nerve fibers whose cell bodies lie in the ipsilateral medullary somatosensory nuclei mediate this effect. These neurons receive inputs from nearby spinal trigeminal tract, fasciculus cuneatus, and facial, vagal, and glossopharyngeal nerve fibers innervating the middle and external ear. CONCLUSIONS: Somatic (craniocervical) modulation of the dorsal cochlear nucleus may account for many previously poorly understood aspects of tinnitus and suggests novel tinnitus treatments.

Adult↗