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PubMed1998

The dorsal cochlear nucleus contributes to a high intensity component of the acoustic startle reflex in rats.

The dorsal cochlear nucleus (DCN) has been shown to project to a region of the nucleus reticularis pontis caudalis (PnC) critical for the evocation of startle in rats, suggesting a possible modulatory influence of the DCN on startle. This study examined the involvement of the DCN in the acoustic startle reflex and various other forms of behavioral plasticity seen with this response. Animals received bilateral electrolytic lesions of the DCN and were tested for acoustic startle responses, background noise facilitation, short-term habituation, prepulse inhibition and facilitation, and fear conditioning. Compared to sham lesioned rats, DCN lesioned rats showed a significant reduction in startle amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL) and normal responses on all other measures. Hence, the DCN appears to contribute to a high intensity component of the acoustic startle response in rats.

Acoustic Stimulation↗
PubMed1988

Distribution of catecholamine fibers in the cochlear nucleus of horseshoe bats and mustache bats.

The glyoxylic-acid-induced fluorescence technique was applied to demonstrate patterns of catecholaminergic innervation within the auditory brainstem of echolocating bats and the house mouse. In the cochlear nucleus of the rufous horseshoe bat (Rhinolophus rouxi) and the mustache bat (Pteronotus parnellii), species-specific catecholaminergic innervation patterns are found that contrast with the relatively homogeneous innervation in the rodent. In both bats the subnuclei of the cochlear nucleus receive a differentially dense supply of catecholaminergic fibers, and within the subnuclei, the catecholamine innervation densities can be correlated with the tonotopic frequency representation. The areas devoted to the high-frequency echolocation calls are less densely innervated than those regions which are responsive to lower frequencies. Apart from this common scheme, there are noteworthy distinctions between the two bats which correlate with specialized cytoarchitectural features of the cochlear nucleus. The marginal cell group, located medially to the anteroventral cochlear nucleus of Pteronotus, receives the densest supply of catecholaminergic fibers of all auditory nuclei. This plexus is formed by a morphologically distinct population of catecholaminergic fibers.

Animals↗
PubMed1980

Changes of acoustic nerve and cochlear nucleus evoked potentials due to repetitive stimulation.

Evoked potential recordings were studied in the acoustic nerve and cochlear nucleus of adult decerebrate cats as a function of the tone duration (1-1500 msec) and the tone repetition rate (0.5/sec-200/sec). Response decrements due to repetitive tonal stimulation were primarily a function of the inter-tone interval. At inter-tone intervals longer than 100 msec, no response decrements were observed in the acoustic nerve or the cochlear nucleus. With shorter inter-tone intervals, reversible response decrements of identical magnitudes ocurred in both the acoustic nerve and the cochlear nucleus evoked potentials. The mechanism of response decrement may be due to depression at the hair cell-acoustic nerve junction.

Acoustic Stimulation↗
PubMed1997

New growth of axons in the cochlear nucleus of adult chinchillas after acoustic trauma.

This study determined the effect of acoustic overstimulation of the adult cochlea on axons in the cochlear nucleus. Chinchillas were exposed to an octave-band noise centered at 4 kHz at 108 dB sound pressure level for 1.75 h. One chinchilla was never exposed to the noise, and several others had one ear protected by an ear plug or prior removal of the malleus and incus. Exposure of unprotected ears caused loss of inner and outer hair cells and myelinated nerve fibers, mostly in the basal half of the cochlea. Cochlear nerve fiber degeneration, ipsilateral to the exposed ears, was traced to regions of the cochlear nucleus representing the damaged parts of the cochlea. In silver impregnations of a deafferented zone in the posteroventral cochlear nucleus, the concentration of axons decreased by 43% after 1 month and by 54% after 2 months. However, by 8 months, the concentration of thinner axons, with diameters of less than 0.46 microm, increased by 46-90% over that at 2 months. The concentration of axons with larger diameters did not change. Between 2 and 8 months small axonal endings appeared next to neuronal cell bodies. This later increase of thinner axons and endings is consistent with a reactive growth of new axons of relatively small diameter. The emergence of small perisomatic boutons suggests that the new axons formed synaptic endings, which might contribute to an abnormal reorganization of the central auditory system and to the pathological changes that accompany acoustic overstimulation.

Animals↗
PubMed1990

Cochlear nucleus anatomy related to central electroauditory prosthesis implantation.

The central electroauditory prosthesis is now used to stimulate the cochlear nuclei to obtain auditory perception in patients with bilateral cochlear nerve transection who are undergoing bilateral acoustic tumor removal. In this study, we used fixed cadaver specimens to identify visible landmarks for accurate placement of the central electroauditory prosthesis through a combined suboccipital-translabyrinthine opening. Histologic features of the regions of probable implantation of the central electroauditory prosthesis were also investigated. We found that the following landmarks might have surgical significance: (1) the tenia of the inferior velum of the fourth ventricle, which crosses the surface of the ventral cochlear nucleus and the vestibulocochlear nerve; (2) the angle between the vestibulocochlear and glossopharyngeal nerves; and (3) the foramen of Luschka. It is suggested that an incision be made in the tenia for insertion of the prosthesis into the lateral recess and eventual placement on the ventral cochlear nucleus surface. To study regions of potential stimulation, we injected ink into different sites on the exposed surface of the cochlear nuclei. We then histologically examined neuronal populations adjacent to the sites. We found that a portion of the ventral cochlear nucleus localized within the lateral recess might be the most appropriate location for placement of the central electroauditory prosthesis.

Cochlea↗
PubMed1992

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Animals↗
PubMed1998

A quantitative profile of the synapses on the stellate cell body and axon in the cochlear nucleus of the chinchilla.

One of the most numerous neurons in the cochlear nucleus is the type I stellate cell. Previous attempts to understand the structural basis for its signal coding assumed that integration of synaptic potentials arising from axodendritic synapses should account for the generation of its response properties. However, the present study documents the importance of excitatory and inhibitory types of synapses on the soma and axon. Retrograde transport of cholera toxin B subunit, injected in the inferior colliculus of chinchillas, was used to label exclusively type I stellate cells in the anteroventral cochlear nucleus. The relative distribution of terminal types by vesicle morphology was pleomorphic > large spherical > flattened > smaller spherical. The somatic perimeter covered by endings ranged from almost none to nearly half. More flattened-vesicle terminals contacted somata in the high-frequency than in the low-frequency region. Eight of twenty axons received endings that contained large spherical vesicles and made asymmetric junctions; half of these extensively apposed the initial segment, forming a collar of presumed excitatory input. Thus, type I stellate cells are a heterogeneous group. Inhibitory synapses probably compose the majority of terminals. Some cells receive mostly inhibitory synapses near the presumed site of the spike generator, but others also have a prominent excitatory input. These findings call for a new look at the mechanisms for signal coding in stellate cells in the auditory system in particular and raise issues concerning the stochastic nature of information processing in sensory systems in general.

Animals↗
PubMed1993

Effect of chronic electrical stimulation on cochlear nucleus neuron size in normal hearing kittens.

Very young cochlear-implant candidates may have undetected islands of residual hearing. Would the maturation of these functioning auditory neurons be affected by chronic cochlear stimulation? This was tested by examining neuron sizes in the cochlear nuclei of young, normal hearing kittens with and without chronic cochlear stimulation. Six animals received bilateral intra- or extracochlear implants and were electrically stimulated unilaterally for periods of 1,000-1,500 hours. After sacrifice, cross-sectional areas of approximately 11,000 neurons somata in the cochlear nuclei were measured with an image-analysis system. There were statistically significant differences between stimulated and unstimulated nuclei, especially the posteroventral cochlear nucleus (PVCN), in individual cats, but the directions of the differences were inconsistent. Overall, there was no significant effect of electrical stimulation on soma size. These results indicate that chronic electrical stimulation of the auditory nerve has no positive or negative trophic effects on otherwise innervated, maturing cochlear nucleus neurons.

Animals↗
PubMed1989

Multiple-channel stimulation of the cochlear nucleus.

To further test the feasibility of a central nervous system auditory prosthesis, the characteristics of the electrically evoked middle latency response were studied in a series of acutely anesthetized pigmented guinea pigs, with multi-channel penetrating cochlear nucleus electrodes placed into the cochlear nucleus under direct visualization. These stimulating electrodes consisted of a silicone substrate, with five stimulating pads each, sputtered with iridium. Monopolar and bipolar stimulation were used. Threshold, latency, and input-output functions of the electrically evoked middle latency response were studied. Systematic differences were observed, depending on the site and parameters of stimulation. Principally, higher currents were required to produce waves of equal amplitude when the electrodes were closely spaced. For near electrode pairs, the maximum wave amplitudies obtainable within the limits of tissue safety were much lower than for distant electrode pairs. The slope of the growth function curve was steeper for widely spaced electrodes than for adjacent sites. Monopolar stimulation demonstrated maximum wave amplitudes with the lowest current intensity, implying current spread to the entire cochlear nucleus with this stimulation montage. In some cases, threshold differences were observed, higher thresholds being associated with closely spaced electrodes. These findings are consistent with simple models of the electric fields expected to be generated by these electrode arrays. The results support the hypothesis that activation of subpopulations of auditory brainstem neurons with multi-channel penetrating microelectrodes is possible.

Animals↗
PubMed1975

Single unit activity in the posteroventral cochlear nucleus of the cat.

Single unit activity in the posteroventral cochlear nucleus (PVCN) was recorded for a variety of stimulus conditions. The units were classified according to their response characteristics. The locations of units were plotted onto a three-dimensional block model of the cochlear nucleus. Certain types of units that responded best to the onsets of stimuli were located predominantly in the octopus cell region of the PVCN. The remainder of the PVCN, which contains a rather heterogeneous collection of small and multipolar cells, was found to contain several types of units with the dominant type being "chopper" units.

Acoustic Stimulation↗
PubMed1998

Kinetic analysis of glycine receptor currents in ventral cochlear nucleus.

Glycine plays an important role as an inhibitory neurotransmitter in the ventral cochlear nucleus. However, little is known about the kinetic behavior of glycine receptors. The present study examines the kinetics of the native inhibitory glycine receptors in neurons of the ventral cochlear nucleus, using outside-out patches from acutely dissociated cells and a fast flow system. Steps into 1 mM glycine revealed fast phases of desensitization with time constants of 13 and 129 ms, that together produced a 40% reduction in current from the peak response. Slower desensitization phases also were observed. After removal of glycine, currents deactivated with two time constants of 15 and 68 ms, and these rates were independent of the glycine concentration between 0.2 and 1 mM. Recovery from desensitization was slow relative to desensitization itself. These results demonstrate that glycine receptors can exhibit faster rates of desensitization and deactivation than previously reported.

Animals↗
PubMed1998

Development of single- and two-tone responses of anteroventral cochlear nucleus neurons in gerbil.

Responses of anteroventral cochlear nucleus (AVCN) neurons in developing gerbils were obtained to single-tone stimuli, and two-tone stimuli elicited by best frequency probes presented over a range of intensities. Neurons displayed Type I, Type I/III, and Type III receptive field patterns. Best frequencies ranged from 1.5 to 10.0 kHz. Two-tone suppression (2TS) was first observed in 5 of 16 neurons examined at 14 dab. and in all neurons examined in gerbils aged 15 to 60 dab. Suppression areas grew larger, and discharge rate reductions became greater with age. Features of the two-tone responses that were highly correlated with single-tone responses across age groups include maximum rate reductions and suppression area thresholds. The intensity level of the CF probe-tone also influenced these features of 2TS. Maximum rate reductions to below spontaneous rate levels of activity were common across age groups. Results suggest that the cochlear amplifier is present and fundamentally adult-like by 15 dab for the regions of the cochlea coding the mid frequencies in gerbil. Over the subsequent week, contributions to the developing two-tone responses by the cochlear amplifier increase slightly. Two-tone responses are influenced by central inhibitory mechanisms as early as 14 dab.

Acoustic Stimulation↗
PubMed1995

Expression of glycine receptor subunits in the cochlear nucleus and superior olivary complex using non-radioactive in-situ hybridization.

The distribution of glycine receptor (GlyR) subunit mRNAs was examined in the cochlear nucleus (CN) and superior olivary complex of 5-6-week-old and 8-10-week-old rats using a non-radioactive in-situ hybridization method. In the younger rats, GlyR alpha 1-, alpha 2-, and alpha 3- and beta-subunits were observed in all major ventral cochlear nucleus (VCN) and superior olivary complex (SOC) neurons, while only alpha 1-, alpha 3- and beta-subunits were observed in dorsal cochlear nucleus (DCN) neurons. In 8-10-week-old rats, GlyR alpha 1-, alpha 3- and beta-subunits were observed in all major CN and SOC neurons, while mRNA for GlyR alpha 2-subunit was not observed. These results indicate that GlyR is being expressed all major CN and SOC neurons, with alpha 1-, alpha 3- and beta-subunit components of the mature receptor and the alpha 2-subunit, a component of the immature GlyR, which is not down-regulated until after 6 weeks of age in most CN and SOC neurons.

Aging↗
PubMed1998

Intracellular responses of the rat anteroventral cochlear nucleus to intracochlear electrical stimulation.

The anteroventral cochlear nucleus (AVCN) is the first central processing site for acoustic information. The influence and extent of convergent auditory nerve input to AVCN neurons was investigated using brief (<0.2 ms) intracochlear electrical activation of spiral ganglion cells. In 40 neurons recorded in vivo, the major intracellular response to stimulation was an excitatory postsynaptic potential (EPSP) with short latency (approximately 1 ms) and fast rise time (<1 ms). Graduated EPSP amplitude increases were also seen with increasing stimulation strength resulting in spike generation. Hyperpolarization followed excitation in most neurons, its extent distinguished three response types: Type I showed no hyperpolarization; Type II and Type III displayed short (<10 ms) and long (>19 ms) duration hyperpolarization, respectively. Hyperpolarization was attributed to an inhibitory postsynaptic potential (IPSP) in addition to spike after hyperpolarization. Neurobiotin filling identified Type I and II neurons as stellate and Type III as bushy cells. These results suggests that AVCN neurons receive direct, possibly convergent, excitatory input from auditory nerves emanating from spiral ganglion cells with hyperpolarization resulting from polysynaptic inhibitory input.

Animals↗
PubMed2005

Spectral edge sensitivity in neural circuits of the dorsal cochlear nucleus.

One possible function of the dorsal cochlear nucleus (DCN) is discrimination of head-related transfer functions (HRTFs), spectral cues used for vertical sound localization. Recent psychophysical and physiological studies suggest that steep, rising spectral edges may be the features used to identify HRTFs. Here we showed, using notch noise and noise band stimuli presented over a range of frequencies, that a subclass of DCN type IV neurons responded with a response peak when the rising spectral edge of a notch or band was aligned near best frequency (BF). This edge sensitivity was correlated with weak or inhibited responses to broadband noise and inhibition in receptive fields at frequencies below BF. Some aspects of the inhibition shaping the response peak, namely inhibition to rising edges below BF and to falling edges at BF, could be explained by the properties of type II interneurons with BFs below those of the type IV neurons. However, many type IV neurons also showed inhibitory responses with the rising spectral edge just above BF, and these responses could not be reproduced by current models of DCN circuitry. Therefore, a new component of the DCN circuit is needed to fully explain the responses to rising spectral edges. This shaping of edge sensitivity by inhibition to rising spectral edges both below and above BF suggests the specialization of DCN for spectral edge coding along the tonotopic gradient.

Acoustic Stimulation↗
PubMed1998

Temporal and binaural properties in dorsal cochlear nucleus and its output tract.

The dorsal cochlear nucleus (DCN) is one of three nuclei at the terminal zone of the auditory nerve. Axons of its projection neurons course via the dorsal acoustic stria (DAS) to the inferior colliculus (IC), where their signals are integrated with inputs from various other sources. The DCN presumably conveys sensitivity to spectral features, and it has been hypothesized that it plays a role in sound localization based on pinna cues. To account for its remarkable spectral properties, a DCN circuit scheme was developed in which three inputs converge onto projection neurons: auditory nerve fibers, inhibitory interneurons, and wide-band inhibitors, which possibly consist of Onset-chopper (Oc) cells. We studied temporal and binaural properties in DCN and DAS and examined whether the temporal properties are consistent with the model circuit. Interneurons (type II) and projection (types III and IV) neurons differed from Oc cells by their longer latencies and temporally nonlinear responses to amplitude-modulated tones. They also showed evidence of early inhibition to clicks. All projection neurons examined were inhibited by stimulation of the contralateral ear, particularly by broadband noise, and this inhibition also had short latency. Because Oc cells had short-latency responses and were well driven by broadband stimuli, we propose that they provide short-latency inhibition to DCN for both ipsilateral and contralateral stimuli. These results indicate more complex temporal behavior in DCN than has previously been emphasized, but they are consistent with the recently described nonlinear behavior to spectral manipulations and with the connectivity scheme deduced from such manipulations.

Action Potentials↗
PubMed1998

Developmental distribution of astrocytic proteins in the rat cochlear nucleus.

To investigate the developmental distribution of cochlear nucleus (CN) astrocytes, we used immunocytochemical localization of glial fibrillary acidic protein (GFAP) and S100beta in rats at 0, 5, 10, 15, 21, 30 postnatal days plus the adult. Differential developmental trends were observed for both proteins. The spatial distribution showed a progressive increase of the number of GFAP-immunoreactive (GFAP-IR) astrocytes during development. GFAP positive cells occurred first in the granule cell domain of the ventral CN and in the molecular cell layer of the dorsal CN, then followed an outside to inside pattern of progression. The GFAP-IR reached an adult distribution 1 month after birth. By contrast with GFAP, the apparition of S100beta-immunoreactivity (S100beta-IR) was abrupt (between 0 and 5 days) followed by a rapid stabilization of density and distribution of IR cells (between 15 and 21 days). The developmental distribution of S100beta-IR cells occurred from the posterodorsal region and progressed toward a rostroventral direction. With contrast to GFAP-IR astrocytes, S100beta-positive cells were mainly restricted to the central part of the CN, while only few IR astrocytes were observed in the granule cell domain of the ventral CN or in the molecular cell layer of the dorsal CN. This differential distribution suggests that both antigens were expressed by two different cell populations at least, it is obvious during the first postnatal week. The gradual expression of GFAP and S100beta is interpreted as reflecting the time course of astrocytic maturation. These data suggest that the maturation of CN astrocytes may be linked to the final maturation of CN neurons.

Animals↗
PubMed1982

Distribution of myo-inositol in the cat cochlear nucleus.

The distribution of myo-inositol, a substance that has been implicated in synaptic transmission, has been mapped within sections of the cat cochlear nucleus as well as some nearby regions. Highest values in the cochlear nucleus were found in regions of granule cells along the periphery of the anteroventral subdivision of the nucleus. Highest values overall were found in the molecular layer of the cerebellar flocculus. A fairly good correlation was found between myo-inositol levels and activities of the enzymes of acetylcholine metabolism in the cat cochlear nucleus, supporting the possibility that myo-inositol may be involved in cholinergic synaptic transmission. No positive correlation was found between myo-inositol levels and the levels of glutamate, aspartate, glycine, or gamma-aminobutyric acid (GABA). The most striking gradient of myo-inositol levels within a region was found in the auditory nerve, where different myo-inositol levels might be related to nerve fibers innervating different parts of the cochlea. The distribution of scyllo-inositol, a stereoisomer of myo-inositol, was also examined, and found to parallel closely the distribution of myo-inositol, with levels 4--5% as high.

Acetylcholinesterase↗