David Ryugo - Academia.edu (original) (raw)
Papers by David Ryugo
Journal of comparative neurology, 2006
Physiological, anatomical and clinical data have demonstrated interactions between somatosensory ... more 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, the dorsal horn of upper cervical spinal segments, and the 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, the 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.
Hearing Research, 2017
Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea... more Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.
Journal of comparative neurology, 2005
The integration of information across sensory modalities enables sound to be processed in the con... more The integration of information across sensory modalities enables sound to be processed in the context of position, movement, and object identity. Inputs to the granule cell domain (GCD) of the cochlear nucleus have been shown to arise from somatosensory brain stem structures, but the nature of the projection from the spinal trigeminal nucleus is unknown.
Otolaryngology-Head and Neck Surgery, Aug 1, 1996
Changes in structure and function of the auditory system can be produced by experimentally manipu... more Changes in structure and function of the auditory system can be produced by experimentally manipulating the sensory environment, and especially dramatic effects result from deprivation procedures. An alternative deprivation strategy utilizes naturally occurring lesions. The congenitally deaf white cat represents an animal model of sensory deprivation because it mimics a form of human deafness called the Scheibe deformity and permits studies of how central neurons react to early-onset cochlear degeneration. We studied the synaptic characteristics of the endbulb of Held, a prominent auditory nerve terminal in the cochlear nucleus. Endbulbs arise from the ascending branch of the auditory nervefiber and contact the cell body of spherical bushy cells. After 6 months, endbulbs of deaf white cats exhibit alterations in structure that are clearly distinguishable from those of normal hearing cats, including a diminution in terminal branching, a reduction in synaptic vesicle density, structural abnormalities in mitochondria, thickening of the pre- and postsynaptic densities, and enlargement of synapse size. The hypertrophied membrane densities are suggestive of a compensatory response to diminished transmitter release. These data reveal that early-onset, long-term deafness produces unambiguous alterations in synaptic structure and may be relevant to rehabilitation strategies that promote aural/oral communication. J. Comp. Neurol. 385:230‐244, 1997. r 1997 Wiley-Liss, Inc.
Cell and Tissue Research, Oct 10, 2014
Data from our laboratory show that the auditory brain is highly malleable by experience. We estab... more Data from our laboratory show that the auditory brain is highly malleable by experience. We establish a base of knowledge that describes the normal structure and workings at the initial stages of the central auditory system. This research is expanded to include the associated pathology in the auditory brain stem created by hearing loss. Utilizing the congenitally deaf white cat, we demonstrate the way that cells, synapses, and circuits are pathologically affected by sound deprivation. We further show that the restoration of auditory nerve activity via electrical stimulation through cochlear implants serves to correct key features of brain pathology caused by hearing loss. The data suggest that rigorous training with cochlear implants and/or hearing aids offers the promise of heretofore unattained benefits.
Springer eBooks, Oct 30, 2010
Page 1. Chapter 9 Descending Connections of Auditory Cortex to the Midbrain and Brain Stem Manuel... more Page 1. Chapter 9 Descending Connections of Auditory Cortex to the Midbrain and Brain Stem Manuel S. Malmierca and David K. Ryugo Abbreviations AI primary auditory cortex AC auditory cortex BDA biotinylated dextran ...
Journal of comparative neurology, May 22, 1990
The auditory (cochlear) ganglion cells of the alligator lizard (Gerrhonotus rnulticarinatus) give... more The auditory (cochlear) ganglion cells of the alligator lizard (Gerrhonotus rnulticarinatus) give rise to two types of peripheral fibers: tectorial fibers, which contact hair cells covered by a tectorial membrane, and free-standing fibers, which contact hair cells without a tectorial membrane. To determine the central projections of these fibers, we applied intracellular and extracellular injections of horseradish peroxidase (HRP) to the peripheral component of the cochlear nerve. After histological processing with diaminobenzidine, individual cochlear nerve fibers could be traced through serial sections with the aid of a light microscope and drawing tube. The projection patterns formed two morphologically distinct groups. Neurons whose peripheral processes contacted tectorial hair cells in the cochlea projected to three divisions of the cochlear nucleus: nucleus magnocellularis lateralis (NML), nucleus magnocellularis medialis (NMM), and nucleus angularis lateralis (NAL). Neurons whose peripheral processes contacted freestanding hair cells projected primarily to the nucleus angularis medialis (NAM), although some also sent a single, thin branch to the NML; these neurons never projected to NAL or NMM. Morphometric comparisons of tectorial and free-standing fibers demonstrate that tectorial fibers have a larger axonal diameter, form a greater number of terminal swellings, and make proportionally more somatic contacts. By correlating the morphologically defined groups with previously reported physiologically defined groups, we conclude that different divisions of the cochlear nucleus are associated with separate frequency ranges and that stimuli in the different frequency ranges may be processed separately in the brain.
Jaro-journal of The Association for Research in Otolaryngology, Jun 1, 2000
branching compared with those of CBA/J and Myo15 ϩ/sh2 mice. Notably, the abnormal endbulbs of My... more branching compared with those of CBA/J and Myo15 ϩ/sh2 mice. Notably, the abnormal endbulbs of Myo15 sh2/sh2 mice do not resemble immature endbulbs The endbulb of Held is a large synaptic ending that of normal-hearing mice, suggesting that deafness does arises from the myelinated auditory nerve fibers. not simply arrest development. Endbulbs exhibit an elaborate pattern of terminal Keywords: deafness, endbulbs of Held, hearing, neurobiobranching and produce extensive contact with the tin, shaker-2 postsynaptic cell body. These structural features appear to underlie the tight coupling between presynaptic activity and postsynaptic spike discharges. As a first step toward understanding the relationship
The acoustic receptor cells in the cochlea contact the peripheral processes of primary auditory n... more The acoustic receptor cells in the cochlea contact the peripheral processes of primary auditory neurons, called spiral ganglion (SG) cells. The central processes of SG cells bundle together to form the auditory nerve (AN) and project into the cochlear nucleus (CN). Through this pathway, transduced acoustic information is conveyed directly as input to the brain. Essentially all of our knowledge concerning the nature of this input via the AN is derived from the myelinated axon of type-I SG cells. Type I neurons innervate inner hair cells exclusively (Kiang et al., 1982) and represent 90–95% of the SG population (Spoendlin, 1971). Virtually nothing is known about the functional properties of the type-II SG cells which innervate outer hair cells and comprise the remainder of the SG population.
Journal of comparative neurology, Apr 1, 2021
Auditory efferents originate in the central auditory system and project to the cochlea. Although ... more Auditory efferents originate in the central auditory system and project to the cochlea. Although the specific anatomy of the olivocochlear (OC) efferents can vary between species, two types of auditory efferents have been identified based upon the general location of their cell bodies and their distinctly different axon terminations in the organ of Corti. In the mouse, the relatively small somata of the lateral (LOC) efferents reside in the lateral superior olive (LSO), have unmyelinated axons, and terminate around ipsilateral inner hair cells (IHCs), primarily against the afferent processes of type I auditory nerve fibers. In contrast, the larger somata of the medial (MOC) efferents are distributed in the ventral nucleus of the trapezoid body (VNTB), have myelinated axons, and terminate bilaterally against the base of multiple outer hair cells (OHCs). Using in vivo retrograde cell body marking, anterograde axon tracing, immunohistochemistry, and electron microscopy, we have identified a group of efferent neurons in mouse, whose cell bodies reside in the ventral nucleus of the lateral lemniscus (VNLL). By virtue of their location, we call them dorsal efferent (DE) neurons. Labeled DE cells were immuno‐negative for tyrosine hydroxylase, glycine, and GABA, but immuno‐positive for choline acetyltransferase. Morphologically, DEs resembled LOC efferents by their small somata, unmyelinated axons, and ipsilateral projection to IHCs. These three classes of efferent neurons all project axons directly to the cochlea and exhibit cholinergic staining characteristics. The challenge is to discover the contributions of this new population of neurons to auditory efferent function.
Frontiers in Neuroanatomy, 2010
Unlike humans, however, cats are altricial animals whose ear canals are closed at birth. By postn... more Unlike humans, however, cats are altricial animals whose ear canals are closed at birth. By postnatal day 30, the ear canal opens and kittens are considered fully hearing. The time course of canal opening is the same for deaf white kittens and normal hearing kittens (Ryugo et al., 2003). Because cats are deaf at birth, we sought to determine whether the emergence of abnormalities at the endbulb of Held synapse in deaf white cats coincided in time with the development of hearing in normal cats. The rationale was that the lack of soundevoked activity would trigger pathologic change in deaf kittens. To this end, we examined the ultrastructure of endbulbs in an age-graded series of deaf kittens and compared the results with those previously reported for normal hearing kittens (Ryugo et al., 2006). MATERIALS AND METHODS SUBJECTS Forty-nine cats contributed new data that were used for this report (Table 1). Structural data were collected from an age-graded series of congenitally deaf cats of either sex that ranged in postnatal age (PN) from newborn (PN-0) to adult. The auditory nerve endings in the cochlear nucleus of two kittens were analyzed at each of the
Brain Research, Apr 1, 2015
Perceptual performance in persons with hearing loss, especially those using devices to restore he... more Perceptual performance in persons with hearing loss, especially those using devices to restore hearing, is not fully predicted by traditional audiometric measurements designed to evaluate the status of peripheral function. The integrity of auditory brainstem synapses may vary with different forms of hearing loss, and differential effects on the auditory nerve-brain interface may have particularly profound consequences for the transfer of sound from ear to brain. Loss of auditory nerve synapses in ventral cochlear nucleus (VCN) has been reported after acoustic trauma, ablation of the organ of Corti, and administration of ototoxic compounds. The effects of gradually acquired forms deafness on these synapses are less well understood. We investigated VCN gross morphology and auditory nerve synapse integrity in DBA/2J mice with early-onset progressive sensorineural hearing loss. Hearing status was confirmed using auditory brainstem response audiometry and acoustic startle responses. We found no change in VCN volume, number of macroneurons, or number of VGLUT1-positive auditory nerve terminals between young adult and older, deaf DBA/2J. Cell-type specific analysis revealed no difference in the number of VGLUT1 puncta contacting bushy and multipolar cell body profiles, but the terminals were smaller in deaf DBA/2J mice. Transmission electron microscopy confirmed the presence of numerous healthy, vesicle-filled auditory nerve synapses in older, deaf DBA/2J mice. The present results suggest that synapses can be preserved over a relatively long time-course in gradually acquired deafness. Elucidating the mechanisms supporting survival of central auditory nerve synapses in models of acquired deafness may reveal new opportunities for therapeutic intervention.
Hearing Research, Jul 1, 1996
Glycine is an inhibitory neurotransmitter and a glutamate cofactor for N-methyl-D-aspartate (NMDA... more Glycine is an inhibitory neurotransmitter and a glutamate cofactor for N-methyl-D-aspartate (NMDA) receptors in the central nervous system. The distribution of glycine in the auditory system will therefore provide clues as to synaptic mechanisms underlying auditory signal processing. Previous studies have reported the immunocytochemical presence of glycine in the dorsal cochlear nucleus of a variety of mammals, but the specificity with respect to particular cell types has proven elusive at the light microscopic level. We sought to identify cell types in the superficial regions of the dorsal cochlear nucleus that were immunoreactive to glycine using light and electron microscopy in the rat. At the light microscopic level, glycine immunoreactivity was present in some but not all medium-sized cells in layers I and II. The somata of pyramidal and granule cells were not stained. At the electron microscopic level, using previously published ultrastructural criteria, we examined the glycine-labeled cells and determined that many but not all cartwheel cells were labeled. We also observed unlabeled unipolar brush cells, Golgi cells, and stellate cells. As some of the labeled cells could not be identified, we could not determine whether unipolar brush cells, Golgi cells or stellate cells had both labeled and unlabeled subpopulations. Our observations indicate that within the population of cartwheel cells, only a subset are glycine-immunoreactive.
Journal of comparative neurology, 2007
Experimental Brain Research, Dec 1, 2003
Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29C, we intra... more Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200-300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high-versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.
Brain Research, May 1, 1975
Experimental Brain Research, Dec 1, 2003
Cortical area Te1 in the rat commonly is associated with primary auditory cortex. It is the sourc... more Cortical area Te1 in the rat commonly is associated with primary auditory cortex. It is the source of direct projections to the inferior colliculus (IC), superior olivary complex (SOC), and the cochlear nucleus (CN). A question that arises is whether these descending pathways derive from a common source or separate populations of cortical neurons. We addressed this question in seven rats by injecting either Diamidino yellow (DiY) or Fast blue (FB) into the IC and injecting the other tracer into the CN (n=4) or SOC (n=3). All injections were made on the left side of the brain. In a sample of sections through area Te1 in both hemispheres, we counted single-and doublelabeled cells. We estimate that IC-projecting cells outnumber those projecting to the CN or SOC by at least a factor of ten. The source of corticofugal pathways to the left IC was heavily biased towards the same side of the brain (ipsi/contra ratio 8€2.5), whereas it was more equally distributed between the two hemispheres for the left CN and SOC (ipsi/contra ratios ranged from 0.7-2.3). Finally, we observed that only 10-20% of those cells filled with a tracer injection in the CN or SOC also contained the tracer injected into the IC. In a previous study, we observed a similarly small percentage of double labeled cells when FB and DiY were injected into the CN and SOC, respectively. Combined with the distinct laminar distribution of IC-, SOC-, and CN-projecting neurons within layer V, the results suggest that these three pathways largely derive from different populations of cortical neurons.
Journal of comparative neurology, Jan 29, 1996
The myelinated fibers of the auditory nerve can be divided into two separate populations on the b... more The myelinated fibers of the auditory nerve can be divided into two separate populations on the basis of sensitivity to sound, average levels of spike activity, and central branching patterns. The synaptic endings of these populations were investigated for the presence of structural specializations that might correlate with levels of neural activity. We applied intracellular recording and staining methods in cats to analyze directly the relationship between spike activity and the structure of synapses using endbulbs of Held, the large synaptic endings in the anteroventral cochlear nucleus. Endbulbs from fibers having low or high levels of activity were examined and compared using light and electron microscopic methods. All endbulbs exhibited relatively large but incomplete coverage by one-to-several lamellae of glial processes. Endbulbs of high activity fibers were large and contained larger mitochondria than endbulbs of low activity fibers. Furthermore, the synapses of high activity endbulbs were on average smaller but more numerous, possessed greater numbers of associated synaptic vesicles, and exhibited greater curvature of their postsynaptic densities. These structural features are hypothesized to reflect specializations that optimize synaptic transmission.
Experimental Neurology, May 1, 1976
Journal of comparative neurology, Feb 22, 1989
Single auditory nerve fibers of type I spiral ganglion cells in cats were electrophysiologically ... more Single auditory nerve fibers of type I spiral ganglion cells in cats were electrophysiologically characterized by recording with micropipettes inserted into the axon and then labeled by intracellular injections of horseradish peroxidase (HRP) through the same pipettes. This method for staining and studying single neurons allowed us to describe structure‐function relationships for labeled endbulbs of Held and the somata of their postsynaptic spherical bushy cells. The silhouette areas of terminal endbulbs and the corresponding somata of spherical bushy cells were determined by planimetry from drawings made with a light microscope and drawing tube. On the presynaptic side, endbulb area is related to fiber characteristic frequency (CF, the frequency to which a fiber is most sensitive) such that the largest endbulbs arise from fibers having CFs between 1 and 4 kHz; smaller endbulbs can arise from fibers of any CF. Endbulb area is not correlated with fiber spontaneous discharge rate (SR). Dividing the endbulb's silhouette area by its silhouette perimeter, however, yields a “form factor” that is a reliable indicator of fiber SR: Endbulbs from fibers of low‐medium SR (≤18 spikes/second) have form factor values less than 0.52, whereas endbulbs of high SR fibers (>18 spikes/second) have values greater than 0.52. This form factor should therefore be predictive of SR groupings in auditory fibers for which physiological data are not available.On the postsynaptic side, the somata of spherical bushy cells receiving endbulbs from low‐medium SR fibers are on average smaller than those receiving endbulbs from high SR fibers. In contrast, the nuclei of the spherical bushy cells are the same size regardless of presynaptic fiber SR. Some of the effects of low‐medium SR fibers on their postsynaptic targets, when compared to those of high SR fibers, appear to be mimicked by effects of experimentally induced deprivation.
Journal of comparative neurology, 2006
Physiological, anatomical and clinical data have demonstrated interactions between somatosensory ... more 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, the dorsal horn of upper cervical spinal segments, and the 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, the 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.
Hearing Research, 2017
Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea... more Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.
Journal of comparative neurology, 2005
The integration of information across sensory modalities enables sound to be processed in the con... more The integration of information across sensory modalities enables sound to be processed in the context of position, movement, and object identity. Inputs to the granule cell domain (GCD) of the cochlear nucleus have been shown to arise from somatosensory brain stem structures, but the nature of the projection from the spinal trigeminal nucleus is unknown.
Otolaryngology-Head and Neck Surgery, Aug 1, 1996
Changes in structure and function of the auditory system can be produced by experimentally manipu... more Changes in structure and function of the auditory system can be produced by experimentally manipulating the sensory environment, and especially dramatic effects result from deprivation procedures. An alternative deprivation strategy utilizes naturally occurring lesions. The congenitally deaf white cat represents an animal model of sensory deprivation because it mimics a form of human deafness called the Scheibe deformity and permits studies of how central neurons react to early-onset cochlear degeneration. We studied the synaptic characteristics of the endbulb of Held, a prominent auditory nerve terminal in the cochlear nucleus. Endbulbs arise from the ascending branch of the auditory nervefiber and contact the cell body of spherical bushy cells. After 6 months, endbulbs of deaf white cats exhibit alterations in structure that are clearly distinguishable from those of normal hearing cats, including a diminution in terminal branching, a reduction in synaptic vesicle density, structural abnormalities in mitochondria, thickening of the pre- and postsynaptic densities, and enlargement of synapse size. The hypertrophied membrane densities are suggestive of a compensatory response to diminished transmitter release. These data reveal that early-onset, long-term deafness produces unambiguous alterations in synaptic structure and may be relevant to rehabilitation strategies that promote aural/oral communication. J. Comp. Neurol. 385:230‐244, 1997. r 1997 Wiley-Liss, Inc.
Cell and Tissue Research, Oct 10, 2014
Data from our laboratory show that the auditory brain is highly malleable by experience. We estab... more Data from our laboratory show that the auditory brain is highly malleable by experience. We establish a base of knowledge that describes the normal structure and workings at the initial stages of the central auditory system. This research is expanded to include the associated pathology in the auditory brain stem created by hearing loss. Utilizing the congenitally deaf white cat, we demonstrate the way that cells, synapses, and circuits are pathologically affected by sound deprivation. We further show that the restoration of auditory nerve activity via electrical stimulation through cochlear implants serves to correct key features of brain pathology caused by hearing loss. The data suggest that rigorous training with cochlear implants and/or hearing aids offers the promise of heretofore unattained benefits.
Springer eBooks, Oct 30, 2010
Page 1. Chapter 9 Descending Connections of Auditory Cortex to the Midbrain and Brain Stem Manuel... more Page 1. Chapter 9 Descending Connections of Auditory Cortex to the Midbrain and Brain Stem Manuel S. Malmierca and David K. Ryugo Abbreviations AI primary auditory cortex AC auditory cortex BDA biotinylated dextran ...
Journal of comparative neurology, May 22, 1990
The auditory (cochlear) ganglion cells of the alligator lizard (Gerrhonotus rnulticarinatus) give... more The auditory (cochlear) ganglion cells of the alligator lizard (Gerrhonotus rnulticarinatus) give rise to two types of peripheral fibers: tectorial fibers, which contact hair cells covered by a tectorial membrane, and free-standing fibers, which contact hair cells without a tectorial membrane. To determine the central projections of these fibers, we applied intracellular and extracellular injections of horseradish peroxidase (HRP) to the peripheral component of the cochlear nerve. After histological processing with diaminobenzidine, individual cochlear nerve fibers could be traced through serial sections with the aid of a light microscope and drawing tube. The projection patterns formed two morphologically distinct groups. Neurons whose peripheral processes contacted tectorial hair cells in the cochlea projected to three divisions of the cochlear nucleus: nucleus magnocellularis lateralis (NML), nucleus magnocellularis medialis (NMM), and nucleus angularis lateralis (NAL). Neurons whose peripheral processes contacted freestanding hair cells projected primarily to the nucleus angularis medialis (NAM), although some also sent a single, thin branch to the NML; these neurons never projected to NAL or NMM. Morphometric comparisons of tectorial and free-standing fibers demonstrate that tectorial fibers have a larger axonal diameter, form a greater number of terminal swellings, and make proportionally more somatic contacts. By correlating the morphologically defined groups with previously reported physiologically defined groups, we conclude that different divisions of the cochlear nucleus are associated with separate frequency ranges and that stimuli in the different frequency ranges may be processed separately in the brain.
Jaro-journal of The Association for Research in Otolaryngology, Jun 1, 2000
branching compared with those of CBA/J and Myo15 ϩ/sh2 mice. Notably, the abnormal endbulbs of My... more branching compared with those of CBA/J and Myo15 ϩ/sh2 mice. Notably, the abnormal endbulbs of Myo15 sh2/sh2 mice do not resemble immature endbulbs The endbulb of Held is a large synaptic ending that of normal-hearing mice, suggesting that deafness does arises from the myelinated auditory nerve fibers. not simply arrest development. Endbulbs exhibit an elaborate pattern of terminal Keywords: deafness, endbulbs of Held, hearing, neurobiobranching and produce extensive contact with the tin, shaker-2 postsynaptic cell body. These structural features appear to underlie the tight coupling between presynaptic activity and postsynaptic spike discharges. As a first step toward understanding the relationship
The acoustic receptor cells in the cochlea contact the peripheral processes of primary auditory n... more The acoustic receptor cells in the cochlea contact the peripheral processes of primary auditory neurons, called spiral ganglion (SG) cells. The central processes of SG cells bundle together to form the auditory nerve (AN) and project into the cochlear nucleus (CN). Through this pathway, transduced acoustic information is conveyed directly as input to the brain. Essentially all of our knowledge concerning the nature of this input via the AN is derived from the myelinated axon of type-I SG cells. Type I neurons innervate inner hair cells exclusively (Kiang et al., 1982) and represent 90–95% of the SG population (Spoendlin, 1971). Virtually nothing is known about the functional properties of the type-II SG cells which innervate outer hair cells and comprise the remainder of the SG population.
Journal of comparative neurology, Apr 1, 2021
Auditory efferents originate in the central auditory system and project to the cochlea. Although ... more Auditory efferents originate in the central auditory system and project to the cochlea. Although the specific anatomy of the olivocochlear (OC) efferents can vary between species, two types of auditory efferents have been identified based upon the general location of their cell bodies and their distinctly different axon terminations in the organ of Corti. In the mouse, the relatively small somata of the lateral (LOC) efferents reside in the lateral superior olive (LSO), have unmyelinated axons, and terminate around ipsilateral inner hair cells (IHCs), primarily against the afferent processes of type I auditory nerve fibers. In contrast, the larger somata of the medial (MOC) efferents are distributed in the ventral nucleus of the trapezoid body (VNTB), have myelinated axons, and terminate bilaterally against the base of multiple outer hair cells (OHCs). Using in vivo retrograde cell body marking, anterograde axon tracing, immunohistochemistry, and electron microscopy, we have identified a group of efferent neurons in mouse, whose cell bodies reside in the ventral nucleus of the lateral lemniscus (VNLL). By virtue of their location, we call them dorsal efferent (DE) neurons. Labeled DE cells were immuno‐negative for tyrosine hydroxylase, glycine, and GABA, but immuno‐positive for choline acetyltransferase. Morphologically, DEs resembled LOC efferents by their small somata, unmyelinated axons, and ipsilateral projection to IHCs. These three classes of efferent neurons all project axons directly to the cochlea and exhibit cholinergic staining characteristics. The challenge is to discover the contributions of this new population of neurons to auditory efferent function.
Frontiers in Neuroanatomy, 2010
Unlike humans, however, cats are altricial animals whose ear canals are closed at birth. By postn... more Unlike humans, however, cats are altricial animals whose ear canals are closed at birth. By postnatal day 30, the ear canal opens and kittens are considered fully hearing. The time course of canal opening is the same for deaf white kittens and normal hearing kittens (Ryugo et al., 2003). Because cats are deaf at birth, we sought to determine whether the emergence of abnormalities at the endbulb of Held synapse in deaf white cats coincided in time with the development of hearing in normal cats. The rationale was that the lack of soundevoked activity would trigger pathologic change in deaf kittens. To this end, we examined the ultrastructure of endbulbs in an age-graded series of deaf kittens and compared the results with those previously reported for normal hearing kittens (Ryugo et al., 2006). MATERIALS AND METHODS SUBJECTS Forty-nine cats contributed new data that were used for this report (Table 1). Structural data were collected from an age-graded series of congenitally deaf cats of either sex that ranged in postnatal age (PN) from newborn (PN-0) to adult. The auditory nerve endings in the cochlear nucleus of two kittens were analyzed at each of the
Brain Research, Apr 1, 2015
Perceptual performance in persons with hearing loss, especially those using devices to restore he... more Perceptual performance in persons with hearing loss, especially those using devices to restore hearing, is not fully predicted by traditional audiometric measurements designed to evaluate the status of peripheral function. The integrity of auditory brainstem synapses may vary with different forms of hearing loss, and differential effects on the auditory nerve-brain interface may have particularly profound consequences for the transfer of sound from ear to brain. Loss of auditory nerve synapses in ventral cochlear nucleus (VCN) has been reported after acoustic trauma, ablation of the organ of Corti, and administration of ototoxic compounds. The effects of gradually acquired forms deafness on these synapses are less well understood. We investigated VCN gross morphology and auditory nerve synapse integrity in DBA/2J mice with early-onset progressive sensorineural hearing loss. Hearing status was confirmed using auditory brainstem response audiometry and acoustic startle responses. We found no change in VCN volume, number of macroneurons, or number of VGLUT1-positive auditory nerve terminals between young adult and older, deaf DBA/2J. Cell-type specific analysis revealed no difference in the number of VGLUT1 puncta contacting bushy and multipolar cell body profiles, but the terminals were smaller in deaf DBA/2J mice. Transmission electron microscopy confirmed the presence of numerous healthy, vesicle-filled auditory nerve synapses in older, deaf DBA/2J mice. The present results suggest that synapses can be preserved over a relatively long time-course in gradually acquired deafness. Elucidating the mechanisms supporting survival of central auditory nerve synapses in models of acquired deafness may reveal new opportunities for therapeutic intervention.
Hearing Research, Jul 1, 1996
Glycine is an inhibitory neurotransmitter and a glutamate cofactor for N-methyl-D-aspartate (NMDA... more Glycine is an inhibitory neurotransmitter and a glutamate cofactor for N-methyl-D-aspartate (NMDA) receptors in the central nervous system. The distribution of glycine in the auditory system will therefore provide clues as to synaptic mechanisms underlying auditory signal processing. Previous studies have reported the immunocytochemical presence of glycine in the dorsal cochlear nucleus of a variety of mammals, but the specificity with respect to particular cell types has proven elusive at the light microscopic level. We sought to identify cell types in the superficial regions of the dorsal cochlear nucleus that were immunoreactive to glycine using light and electron microscopy in the rat. At the light microscopic level, glycine immunoreactivity was present in some but not all medium-sized cells in layers I and II. The somata of pyramidal and granule cells were not stained. At the electron microscopic level, using previously published ultrastructural criteria, we examined the glycine-labeled cells and determined that many but not all cartwheel cells were labeled. We also observed unlabeled unipolar brush cells, Golgi cells, and stellate cells. As some of the labeled cells could not be identified, we could not determine whether unipolar brush cells, Golgi cells or stellate cells had both labeled and unlabeled subpopulations. Our observations indicate that within the population of cartwheel cells, only a subset are glycine-immunoreactive.
Journal of comparative neurology, 2007
Experimental Brain Research, Dec 1, 2003
Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29C, we intra... more Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200-300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high-versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.
Brain Research, May 1, 1975
Experimental Brain Research, Dec 1, 2003
Cortical area Te1 in the rat commonly is associated with primary auditory cortex. It is the sourc... more Cortical area Te1 in the rat commonly is associated with primary auditory cortex. It is the source of direct projections to the inferior colliculus (IC), superior olivary complex (SOC), and the cochlear nucleus (CN). A question that arises is whether these descending pathways derive from a common source or separate populations of cortical neurons. We addressed this question in seven rats by injecting either Diamidino yellow (DiY) or Fast blue (FB) into the IC and injecting the other tracer into the CN (n=4) or SOC (n=3). All injections were made on the left side of the brain. In a sample of sections through area Te1 in both hemispheres, we counted single-and doublelabeled cells. We estimate that IC-projecting cells outnumber those projecting to the CN or SOC by at least a factor of ten. The source of corticofugal pathways to the left IC was heavily biased towards the same side of the brain (ipsi/contra ratio 8€2.5), whereas it was more equally distributed between the two hemispheres for the left CN and SOC (ipsi/contra ratios ranged from 0.7-2.3). Finally, we observed that only 10-20% of those cells filled with a tracer injection in the CN or SOC also contained the tracer injected into the IC. In a previous study, we observed a similarly small percentage of double labeled cells when FB and DiY were injected into the CN and SOC, respectively. Combined with the distinct laminar distribution of IC-, SOC-, and CN-projecting neurons within layer V, the results suggest that these three pathways largely derive from different populations of cortical neurons.
Journal of comparative neurology, Jan 29, 1996
The myelinated fibers of the auditory nerve can be divided into two separate populations on the b... more The myelinated fibers of the auditory nerve can be divided into two separate populations on the basis of sensitivity to sound, average levels of spike activity, and central branching patterns. The synaptic endings of these populations were investigated for the presence of structural specializations that might correlate with levels of neural activity. We applied intracellular recording and staining methods in cats to analyze directly the relationship between spike activity and the structure of synapses using endbulbs of Held, the large synaptic endings in the anteroventral cochlear nucleus. Endbulbs from fibers having low or high levels of activity were examined and compared using light and electron microscopic methods. All endbulbs exhibited relatively large but incomplete coverage by one-to-several lamellae of glial processes. Endbulbs of high activity fibers were large and contained larger mitochondria than endbulbs of low activity fibers. Furthermore, the synapses of high activity endbulbs were on average smaller but more numerous, possessed greater numbers of associated synaptic vesicles, and exhibited greater curvature of their postsynaptic densities. These structural features are hypothesized to reflect specializations that optimize synaptic transmission.
Experimental Neurology, May 1, 1976
Journal of comparative neurology, Feb 22, 1989
Single auditory nerve fibers of type I spiral ganglion cells in cats were electrophysiologically ... more Single auditory nerve fibers of type I spiral ganglion cells in cats were electrophysiologically characterized by recording with micropipettes inserted into the axon and then labeled by intracellular injections of horseradish peroxidase (HRP) through the same pipettes. This method for staining and studying single neurons allowed us to describe structure‐function relationships for labeled endbulbs of Held and the somata of their postsynaptic spherical bushy cells. The silhouette areas of terminal endbulbs and the corresponding somata of spherical bushy cells were determined by planimetry from drawings made with a light microscope and drawing tube. On the presynaptic side, endbulb area is related to fiber characteristic frequency (CF, the frequency to which a fiber is most sensitive) such that the largest endbulbs arise from fibers having CFs between 1 and 4 kHz; smaller endbulbs can arise from fibers of any CF. Endbulb area is not correlated with fiber spontaneous discharge rate (SR). Dividing the endbulb's silhouette area by its silhouette perimeter, however, yields a “form factor” that is a reliable indicator of fiber SR: Endbulbs from fibers of low‐medium SR (≤18 spikes/second) have form factor values less than 0.52, whereas endbulbs of high SR fibers (>18 spikes/second) have values greater than 0.52. This form factor should therefore be predictive of SR groupings in auditory fibers for which physiological data are not available.On the postsynaptic side, the somata of spherical bushy cells receiving endbulbs from low‐medium SR fibers are on average smaller than those receiving endbulbs from high SR fibers. In contrast, the nuclei of the spherical bushy cells are the same size regardless of presynaptic fiber SR. Some of the effects of low‐medium SR fibers on their postsynaptic targets, when compared to those of high SR fibers, appear to be mimicked by effects of experimentally induced deprivation.