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D.k. Morest - One of the best experts on this subject based on the ideXlab platform.

  • Degeneration in the ventral Cochlear Nucleus after severe noise damage in mice
    Journal of neuroscience research, 2011
    Co-Authors: J. Feng, J. Bendiske, D.k. Morest
    Abstract:

    To study the mechanisms of noise-induced hearing loss and the phantom noise, or tinnitus, often associated with it, we studied a mouse model of noise damage designed for reproducible and quantitative structural analyses. We selected the Posteroventral Cochlear Nucleus, which has shown considerable plasticity in past studies, and correlated its changes with the distribution of NT3. We used volume change, optical density analysis, and microscopic cluster analysis to measure the degeneration after noise exposure. There was a fluctuation pattern in the reorganization of nerve terminals. The data suggest that the source and size of the nerve terminals affect their capacity for regeneration. We hypothesize that the deafferentation of VCN is the structural basis of noise-induced tinnitus. In addition the immuno-fluorescent data show a possible connection between NT3 and astrocytes. There appears to be a compensatory process in the supporting glial cells during this degeneration. Glia may play a role in the mechanisms of noise-induced hearing loss.

  • Quantitative study of degeneration and new growth of axons and synaptic endings in the chinchilla Cochlear Nucleus after acoustic overstimulation.
    Journal of neuroscience research, 2004
    Co-Authors: J.j. Kim, D.k. Morest, Jeffrey B. Gross, Steven J. Potashner
    Abstract:

    To determine if acoustic overstimulation altered synaptic connections in the Cochlear Nucleus, anesthetized adult chinchillas, with one ear protected by a silicone plug, were exposed for 3 hr to a 108-dB octave-band noise, centered at 4 kHz, and allowed to survive for periods up to 32 weeks. This exposure led to Cochlear damage in the unprotected ear, mainly in the basal regions of the organ of Corti. The anterior part of the ipsilateral Posteroventral Cochlear Nucleus consistently contained a band of degenerating axons and terminals, in which electron microscopic analysis revealed substantial losses of axons and synaptic terminals with excitatory and inhibitory cytology. The losses were significant after 1 week's survival and progressed for 16-24 weeks after exposure. By 24-32 weeks, a new growth of these structures produced a resurgence in the number of axons and terminals. The net number of excitatory endings fully recovered, but the quantity with inhibitory cytology was only partially recouped. Neuronal somata lost both excitatory and inhibitory endings at first and later recovered a full complement of excitatory but not inhibitory terminals. Dendrites suffered a net loss of both excitatory and inhibitory endings. Excitatory and inhibitory terminals with unidentified postsynaptic targets in the neuropil declined, then increased in number, with excitatory terminals exhibiting a greater recovery. These findings are consistent with a loss and regrowth of synaptic endings and with a reorganization of synaptic connections that favors excitation.

  • New growth of axons in the Cochlear Nucleus of adult chinchillas after acoustic trauma.
    Experimental neurology, 1997
    Co-Authors: M. Bilak, J.j. Kim, Steven J. Potashner, B.a. Bohne, D.k. Morest
    Abstract:

    Abstract 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 μm, 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.

  • A physiological and structural study of neuron types in the Cochlear Nucleus. II. Neuron types and their structural correlation with response properties.
    The Journal of comparative neurology, 1994
    Co-Authors: E.-m. Ostapoff, Jane J. Feng, D.k. Morest
    Abstract:

    The present study examined the morphological cell types of neurons labeled with intracellular horseradish peroxidase injections, many of them following electrophysiological recordings in the Cochlear Nucleus of gerbils and chinchillas. Most of the subdivisions and neuronal types previously described in the cat were identified in the present material, including spherical and globular bushy cells, stellate, bushy multipolar, elongate, octopus, and giant cells in the ventral Cochlear Nucleus, and a cartwheel cell in the dorsal Cochlear Nucleus. In many cases these structurally distinct neurons were correlated with their characteristic responses to stimulation by sound or intracellular injection of depolarizing current. The dendritic terminals of the elongate, antenniform, and clavate cells of the Posteroventral Cochlear Nucleus link each of these cell types with neighboring structures in distinct patterns, which may provide a basis for differences in synaptic organization. These cell types differ from each other and from the stellate cells of the anteroventral Cochlear Nucleus. Despite their heterogeneous morphology, most of these neurons had a regular discharge in response to stimulation (choppers). Irregularly firing neurons (primary-like) had very different structures, e.g., the spherical and globular bushy cells and the bushy multipolar neuron. They, too, represent a heterogeneous population. An onset neuron was identified as an octopus cell. This paper compares the morphological observations with the electrophysiological properties of different cell types reported in a companion paper (Feng et al. [1994] J. Comp. Neurol.). Together, these findings imply that response properties may be partially independent of neuronal structure. Morphologically distinct neurons can generate similar temporal patterns in response to simple acoustic stimuli. Nevertheless, the synaptic organization of these different neuron types, including their connections, would be expected to affect or alter the cells' responses to appropriate stimuli. The possibility is raised that membrane properties and synaptic organization complement and interact with each other.

H K Happe - One of the best experts on this subject based on the ideXlab platform.

  • Cholinergic receptors: dual roles in transduction and plasticity
    Hearing Research, 2000
    Co-Authors: B J Morley, H K Happe
    Abstract:

    Abstract The regional distributions and possible functions of nicotinic acetylcholine receptors (nAChRs) in the developing and adult auditory rat brain are reviewed. The predominant nAChR in the auditory brainstem is the α7 homomeric receptor. α7 mRNA and protein are expressed in selected regions of the Cochlear Nucleus (CN), inferior colliculus (IC), medial superior olive, lateral superior olive, ventral Nucleus of the lateral lemniscus and superior paraolivary Nucleus. Peak expression of mRNA and protein occurs by the second postnatal week in most auditory brainstem areas. In contrast, the α3 and β4 nicotinic subunits are expressed in the embryo and early in postnatal development in the CN and IC, but not other brainstem nuclei. Of particular interest is the octopus cell region of the Posteroventral Cochlear Nucleus (PVCN). α3 and β4 are down-regulated in the octopus cell region about postnatal day 10, which is the age that α7 is at peak expression. NAChRs play important roles in transduction and in regulating intracellular calcium. The ability of the α7 receptor to synchronize synaptic activity and stabilize synapses makes it a prime candidate as a mechanism underlying homeostatic plasticity in the auditory system.

  • Cholinergic receptors: dual roles in transduction and plasticity.
    Hearing research, 2000
    Co-Authors: B J Morley, H K Happe
    Abstract:

    The regional distributions and possible functions of nicotinic acetylcholine receptors (nAChRs) in the developing and adult auditory rat brain are reviewed. The predominant nAChR in the auditory brainstem is the alpha7 homomeric receptor. alpha7 mRNA and protein are expressed in selected regions of the Cochlear Nucleus (CN), inferior colliculus (IC), medial superior olive, lateral superior olive, ventral Nucleus of the lateral lemniscus and superior paraolivary Nucleus. Peak expression of mRNA and protein occurs by the second postnatal week in most auditory brainstem areas. In contrast, the alpha3 and beta4 nicotinic subunits are expressed in the embryo and early in postnatal development in the CN and IC, but not other brainstem nuclei. Of particular interest is the octopus cell region of the Posteroventral Cochlear Nucleus (PVCN). alpha3 and beta4 are down-regulated in the octopus cell region about postnatal day 10, which is the age that alpha7 is at peak expression. NAChRs play important roles in transduction and in regulating intracellular calcium. The ability of the alpha7 receptor to synchronize synaptic activity and stabilize synapses makes it a prime candidate as a mechanism underlying homeostatic plasticity in the auditory system.

Donald A. Godfrey - One of the best experts on this subject based on the ideXlab platform.

  • Volumes of Cochlear Nucleus regions in rodents
    Hearing research, 2016
    Co-Authors: Donald A. Godfrey, Augustine C. Lee, Walter D. Hamilton, Louis C. Benjamin, Shilpa Vishwanath, Hermann Simo, Lynn M. Godfrey, Abdurrahman I.a.a. Mustapha, Rickye S. Heffner
    Abstract:

    The Cochlear Nucleus receives all the coded information about sound from the cochlea and is the source of auditory information for the rest of the central auditory system. As such, it is a critical auditory Nucleus. The sizes of the Cochlear Nucleus as a whole and its three major subdivisions - anteroventral Cochlear Nucleus (AVCN), Posteroventral Cochlear Nucleus (PVCN), and dorsal Cochlear Nucleus (DCN) - have been measured in a large number of mammals, but measurements of its subregions at a more detailed level for a variety of species have not previously been made. Size measurements are reported here for the summed granular regions, DCN layers, AVCN, PVCN, and interstitial Nucleus in 15 different rodent species, as well as a lagomorph, carnivore, and small primate. This further refinement of measurements is important because the granular regions and superficial layers of the DCN appear to have some different functions than the other Cochlear Nucleus regions. Except for DCN layers in the mountain beaver, all regions were clearly identifiable in all the animals studied. Relative regional size differences among most of the rodents, and even the 3 non-rodents, were not large and did not show a consistent relation to their wide range of lifestyles and hearing parameters. However, the mountain beaver, and to a lesser extent the pocket gopher, two rodents that live in tunnel systems, had relative sizes of summed granular regions and DCN molecular layer distinctly larger than those of the other mammals. Among all the mammals studied, there was a high correlation between the size per body weight of summed granular regions and that of the DCN molecular layer, consistent with other evidence for a close relationship between granule cells and superficial DCN neurons.

  • Cochlear ablation effects on amino acid levels in the chinchilla Cochlear Nucleus
    Neuroscience, 2015
    Co-Authors: Donald A. Godfrey, Kejian Chen, M.a. Godfrey, Augustine C. Lee, Hermann Simo, S.p. Crass, D. Shipp, K.t. Robinson
    Abstract:

    Abstract 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 2 weeks 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.
    Neuroscience, 2008
    Co-Authors: Donald A. Godfrey, Kejian Chen, M.a. Godfrey, Y.-m. Jin, K.t. Robinson, C. Hair
    Abstract:

    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.

  • Amino acid concentrations in chinchilla Cochlear Nucleus at different times after carboplatin treatment
    Hearing research, 2005
    Co-Authors: Donald A. Godfrey, Kejian Chen, Matthew A Godfrey, Da-lian Ding, Richard Salvi
    Abstract:

    Abstract 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 γ-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.

  • Effects of carboplatin on amino acid chemistry in chinchilla Cochlear Nucleus.
    Hearing research, 2002
    Co-Authors: Donald A. Godfrey, Matthew A Godfrey, Da-lian Ding, Richard Salvi
    Abstract:

    Carboplatin, a drug widely used against solid head and neck tumors, selectively destroys Cochlear inner hair cells and type I auditory nerve fibers in chinchilla. This should affect neurotransmitter chemistry, involving amino acids, where the type I auditory nerve fibers terminate in the Cochlear Nucleus. Using microdissection combined with high-performance liquid chromatography, amino acid concentrations were mapped in the Cochlear nuclei of chinchillas injected intraperitoneally 6-8 weeks earlier with 100 mg/kg carboplatin and in those of control animals. Glutamate concentrations were 23% lower in the anteroventral Cochlear Nucleus (AVCN) and 40% lower in the Posteroventral Cochlear Nucleus (PVCN) of carboplatin-injected chinchillas as compared to controls, while aspartate concentrations were 18% lower in AVCN and 27% lower in PVCN. Using a fluorometric assay, activities of glutaminase, an enzyme which catalyzes glutamate synthesis, were 30% lower in AVCN and 38% lower in PVCN of carboplatin-injected chinchillas. Concentrations of glutamine, gamma-aminobutyrate, and glycine were also lower in some ventral and dorsal Cochlear Nucleus regions of treated animals. These changes probably result mainly from both primary and later effects of reduced type I auditory nerve fiber input to the Cochlear Nucleus.

B J Morley - One of the best experts on this subject based on the ideXlab platform.

  • Cholinergic receptors: dual roles in transduction and plasticity
    Hearing Research, 2000
    Co-Authors: B J Morley, H K Happe
    Abstract:

    Abstract The regional distributions and possible functions of nicotinic acetylcholine receptors (nAChRs) in the developing and adult auditory rat brain are reviewed. The predominant nAChR in the auditory brainstem is the α7 homomeric receptor. α7 mRNA and protein are expressed in selected regions of the Cochlear Nucleus (CN), inferior colliculus (IC), medial superior olive, lateral superior olive, ventral Nucleus of the lateral lemniscus and superior paraolivary Nucleus. Peak expression of mRNA and protein occurs by the second postnatal week in most auditory brainstem areas. In contrast, the α3 and β4 nicotinic subunits are expressed in the embryo and early in postnatal development in the CN and IC, but not other brainstem nuclei. Of particular interest is the octopus cell region of the Posteroventral Cochlear Nucleus (PVCN). α3 and β4 are down-regulated in the octopus cell region about postnatal day 10, which is the age that α7 is at peak expression. NAChRs play important roles in transduction and in regulating intracellular calcium. The ability of the α7 receptor to synchronize synaptic activity and stabilize synapses makes it a prime candidate as a mechanism underlying homeostatic plasticity in the auditory system.

  • Cholinergic receptors: dual roles in transduction and plasticity.
    Hearing research, 2000
    Co-Authors: B J Morley, H K Happe
    Abstract:

    The regional distributions and possible functions of nicotinic acetylcholine receptors (nAChRs) in the developing and adult auditory rat brain are reviewed. The predominant nAChR in the auditory brainstem is the alpha7 homomeric receptor. alpha7 mRNA and protein are expressed in selected regions of the Cochlear Nucleus (CN), inferior colliculus (IC), medial superior olive, lateral superior olive, ventral Nucleus of the lateral lemniscus and superior paraolivary Nucleus. Peak expression of mRNA and protein occurs by the second postnatal week in most auditory brainstem areas. In contrast, the alpha3 and beta4 nicotinic subunits are expressed in the embryo and early in postnatal development in the CN and IC, but not other brainstem nuclei. Of particular interest is the octopus cell region of the Posteroventral Cochlear Nucleus (PVCN). alpha3 and beta4 are down-regulated in the octopus cell region about postnatal day 10, which is the age that alpha7 is at peak expression. NAChRs play important roles in transduction and in regulating intracellular calcium. The ability of the alpha7 receptor to synchronize synaptic activity and stabilize synapses makes it a prime candidate as a mechanism underlying homeostatic plasticity in the auditory system.

M. Christian Brown - One of the best experts on this subject based on the ideXlab platform.

  • Ultrastructure of synaptic input to medial olivoCochlear neurons.
    The Journal of comparative neurology, 2006
    Co-Authors: Thane E. Benson, M. Christian Brown
    Abstract:

    Medial olivoCochlear (MOC) neurons project from the brain to the cochlea to form the efferent limb of the MOC reflex. To study synaptic inputs to MOC neurons, we retrogradely labeled these neurons using horseradish peroxidase injections into the cochlea. Labeled neurons were identified in the ventral Nucleus of the trapezoid body and documented with the light microscope before being studied with serial-section electron microscopy. MOC somata and dendrites were innervated by three different types of synapses, distinguished as either having: 1) large, round synaptic vesicles and forming asymmetric contacts; 2) small, round vesicles plus a few dense core vesicles and forming asymmetric contacts; or 3) pleomorphic vesicles and forming symmetric contacts. The first two types were the most frequent on somata. Acetylcholinesterase-stained material confirmed that the type containing large, round vesicles is most common on dendrites. We kept track of the synaptic terminals in serial sections and compiled them into three-dimensional swellings. Swellings with large, round vesicles formed up to seven synapses per swelling, were largest in size, and sometimes formed complex arrangements engulfing spines of MOC neurons. Swellings with small, round vesicles formed up to four synapses per swelling. The morphology of this type of synapse, and the moderate sizes of the swellings forming it, suggests that it originates from Posteroventral Cochlear Nucleus stellate/multipolar neurons. This input may thus provide the sound-evoked input to MOC neurons that causes their reflexive response to sound. J. Comp. Neurol. 499:244–257, 2006. © 2006 Wiley-Liss, Inc.

  • Medial OlivoCochlear Reflex Interneurons Are Located in the Posteroventral Cochlear Nucleus: A Kainic Acid Lesion Study in Guinea Pigs
    The Journal of comparative neurology, 2005
    Co-Authors: Ronald K. De Venecia, M. Charles Liberman, John J. Guinan, M. Christian Brown
    Abstract:

    The medial olivoCochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the Cochlear Nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the Cochlear Nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(2)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the Posteroventral Cochlear Nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons.

  • Central trajectories of type II (thin) fibers of the auditory nerve in cats
    Hearing research, 1994
    Co-Authors: Yvette V. Morgan, David K. Ryugo, M. Christian Brown
    Abstract:

    Abstract This paper describes the central projections of thin fibers of the auditory nerve in cats. Both thin (type II) and thick (type I) fibers are labeled by extracellular injections of horseradish peroxidase (HRP) into the auditory nerve. Type I and almost all type II fibers bifurcate upon reaching the auditory nerve root of the Cochlear Nucleus. For a given bundle of auditory nerve fibers labeled by a discrete injection of HRP, bifurcations of type II and type I fibers are restricted to a narrow region of the nerve root. After the bifurcation, the pathways of type II branches within the anteroventral Cochlear Nucleus (AVCN) and Posteroventral Cochlear Nucleus (PVCN) are similar to those of type I branches. This similarity in bifurcation and course of type I and type II fibers was observed in the ventral as well as dorsal parts of the ventral Cochlear Nucleus. The complete axonal course of most type II fibers could not be reconstructed, however, due to fading of the reaction product. Type II fibers produce very few collaterals in the Cochlear Nucleus (CN), but possess many ‘en passant’ swellings along their main processes and collaterals. Compared with type II fibers previously studied in mice (Berglund and Brown, 1989; 1994; Brown and Ledwith, 1990), cat type II fibers are similar in their general projections within the main body of the Nucleus and in the frequency of ‘en passant’ swellings per length of fiber, but cat fibers have a higher percentage of ‘complex’ or pedunculated ‘en passant’ swellings.