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Hearing Research Aug 2008The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates...
The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates for cochlear implants and influence implant efficacy. Stem cells offer the potential for improving the function of cochlear prostheses and increasing the candidate pool by replacing lost auditory nerve. The first phase of studies for stem cell replacement of auditory nerve has examined the in vitro survival and differentiation as well as in vivo differentiation and survival of exogenous embryonic and tissue stem cells placed into scala tympani and/or modiolus. These studies are reviewed and new results on in vivo placement of B-5 mouse embryonic stem cells into scala tympani of the guinea pig cochleae with differentiation into a glutamatergic neuronal phenotype are presented. Research on the integration and connections of stem cell derived neurons in the cochlea is described. Finally, an alternative approach is considered, based on the use of endogenous progenitors rather than exogenous stem cells, with a review of promising findings that have identified stem cell-like progenitors in cochlear and vestibular tissues to provide the potential for auditory nerve replacement.
Topics: Animals; Cell Differentiation; Cell Survival; Cochlear Nerve; Deafness; Embryonic Stem Cells; Guinea Pigs; Mice; Mice, Inbred Strains; Models, Animal; Scala Tympani; Stem Cell Transplantation
PubMed: 18585449
DOI: 10.1016/j.heares.2008.06.004 -
Hearing Research Sep 2013People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this... (Review)
Review
People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this difficulty may be caused by changes in auditory processing of the rapidly-varying temporal fine structure (TFS) of acoustic signals. In this paper, we review the presently known effects of sensorineural hearing loss on processing of TFS and slower envelope modulations in the peripheral auditory system of mammals. Cochlear damage has relatively subtle effects on phase locking by auditory-nerve fibers to the temporal structure of narrowband signals under quiet conditions. In background noise, however, sensorineural loss does substantially reduce phase locking to the TFS of pure-tone stimuli. For auditory processing of broadband stimuli, sensorineural hearing loss has been shown to severely alter the neural representation of temporal information along the tonotopic axis of the cochlea. Notably, auditory-nerve fibers innervating the high-frequency part of the cochlea grow increasingly responsive to low-frequency TFS information and less responsive to temporal information near their characteristic frequency (CF). Cochlear damage also increases the correlation of the response to TFS across fibers of varying CF, decreases the traveling-wave delay between TFS responses of fibers with different CFs, and can increase the range of temporal modulation frequencies encoded in the periphery for broadband sounds. Weaker neural coding of temporal structure in background noise and degraded coding of broadband signals along the tonotopic axis of the cochlea are expected to contribute considerably to speech perception problems in people with sensorineural hearing loss. This article is part of a Special Issue entitled "Annual Reviews 2013".
Topics: Acoustic Stimulation; Animals; Auditory Perception; Cochlea; Cochlear Nerve; Hearing Loss, Sensorineural; Humans; Speech Perception
PubMed: 23376018
DOI: 10.1016/j.heares.2013.01.014 -
Journal of Neurophysiology Mar 2018Declines in auditory nerve (AN) function contribute to suprathreshold auditory processing and communication deficits in individuals with normal hearing, hearing loss,...
Declines in auditory nerve (AN) function contribute to suprathreshold auditory processing and communication deficits in individuals with normal hearing, hearing loss, hyperacusis, and tinnitus. Procedures to characterize AN loss or dysfunction in humans are limited. We report several novel complementary metrics using the compound action potential (CAP), a direct measure of summated AN activity. Together, these metrics may be used to characterize AN function noninvasively in humans. We examined how these metrics change with stimulus intensity and interpreted these changes within a framework of known physiological properties of the basilar membrane and AN. Our results reveal how neural synchrony and the recruitment of AN fibers with longer first-spike latencies likely contribute to the CAP, affect auditory processing, and differ with noise exposure history in younger adults with normal pure-tone thresholds. Moving forward, this new battery of metrics provides a crucial step toward new diagnostics of AN function in humans. NEW & NOTEWORTHY Loss or inactivity of auditory nerve (AN) fibers is thought to contribute to suprathreshold auditory processing deficits, but evidence-based methods to assess these effects are not available. We describe several novel metrics that together may be used to quantify neural synchrony and characterize AN function in humans.
Topics: Acoustic Stimulation; Action Potentials; Adult; Auditory Threshold; Cochlear Nerve; Female; Humans; Male; Models, Neurological; Reflex, Acoustic; Young Adult
PubMed: 29187555
DOI: 10.1152/jn.00638.2017 -
Journal of Neurophysiology Aug 2013
Topics: Animals; Cochlear Nerve; Female; Hearing Loss, Noise-Induced; Vestibulocochlear Nerve Diseases
PubMed: 23636727
DOI: 10.1152/jn.00292.2013 -
Neurobiology of Aging Jul 2022Aging is associated with auditory nerve (AN) functional deficits and decreased inhibition in the central auditory system, amplifying central responses in a process...
Aging is associated with auditory nerve (AN) functional deficits and decreased inhibition in the central auditory system, amplifying central responses in a process referred to here as central gain. Although central gain increases response amplitudes, central gain may not restore disrupted response timing. In this translational study, we measured responses putatively generated by the AN and auditory midbrain in younger and older mice and humans. We hypothesized that older mice and humans exhibit increased central gain without an improvement in inter-trial synchrony in the midbrain. Our data demonstrated greater age-related deficits in AN response amplitudes than auditory midbrain response amplitudes, as shown by significant interactions between inferred neural generator and age group, indicating increased central gain in auditory midbrain. However, synchrony decreases with age in both the AN and midbrain responses. These results reveal age-related increases in central gain without concomitant improvements in synchrony, consistent with those predictions based on decreases in inhibition. Persistent decreases in synchrony may contribute to auditory processing deficits in older mice and humans.
Topics: Acoustic Stimulation; Aging; Auditory Perception; Brain Stem; Cochlear Nerve; Evoked Potentials, Auditory, Brain Stem; Humans
PubMed: 35468552
DOI: 10.1016/j.neurobiolaging.2022.03.014 -
Internal Medicine (Tokyo, Japan) 2012We herein report a 26-year-old man with Guillain-Barré Syndrome (GBS) coexisting facial nerve palsy (FP) and deafness. He developed deafness, facial weakness, and limb...
We herein report a 26-year-old man with Guillain-Barré Syndrome (GBS) coexisting facial nerve palsy (FP) and deafness. He developed deafness, facial weakness, and limb weakness and numbness. Neurological examination showed facial diplegia, bilateral hypoacusia, areflexia and sensorimotor deficits in the distal limbs. The nerve conduction study findings supported the diagnosis of the demyelinating polyneuropathy. An audiogram revealed sensorineural hearing loss of 40-50 dB. Auditory brainstem responses disclosed no elicitation of waves I to IV on both sides. Magnetic resonance imaging depicted abnormal enhancement in bilateral facial and acoustic nerves. Physicians should pay more attention to auditory dysfunction in GBS patients with FP.
Topics: Adult; Cochlear Nerve; Comorbidity; Facial Nerve; Facial Paralysis; Guillain-Barre Syndrome; Hearing Loss, Sudden; Humans; Magnetic Resonance Imaging; Male; Neural Conduction; Radiographic Image Enhancement
PubMed: 22975563
DOI: 10.2169/internalmedicine.51.7737 -
The Journal of Neuroscience : the... Jan 2014The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion...
The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of α2δ3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. α2δ3(-/-) mice learned to discriminate pure tones, but they failed to discriminate temporally structured amplitude-modulated tones. Light and electron microscopy analyses revealed reduced levels of presynaptic Ca(2+) channels and smaller auditory nerve fiber terminals contacting cochlear nucleus bushy cells. Juxtacellular in vivo recordings of sound-evoked activity in α2δ3(-/-) mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the α2δ3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.
Topics: Animals; Auditory Perceptual Disorders; Brain Stem; Calcium Channels; Cochlear Nerve; Discrimination Learning; Electrophysiology; Evoked Potentials, Auditory, Brain Stem; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Reverse Transcriptase Polymerase Chain Reaction; Spiral Ganglion; Synapses; Synaptic Transmission
PubMed: 24403143
DOI: 10.1523/JNEUROSCI.3085-13.2014 -
Assessment of responses to cochlear implant stimulation at different levels of the auditory pathway.Hearing Research Apr 2015This paper reviews characteristics of both the electrically evoked compound action potential (ECAP) and analogous measures of cortically evoked responses (CAEP) to... (Review)
Review
This paper reviews characteristics of both the electrically evoked compound action potential (ECAP) and analogous measures of cortically evoked responses (CAEP) to electrical stimulation in cochlear implant users. Specific comparisons are made between the two levels of processing for measures of threshold, growth of responses with increasing stimulus level, changes in stimulation electrode and, finally, in temporal response properties. The results are interpreted in a context that ECAPs primarily reflect the characteristics of the electrode-neural interface for an individual ear. CAEPs clearly are dependent on those peripheral responses but also reflect differences in central processing among individual implant users. The potential applicability of combined measures in clinical situations is discussed. This article is part of a Special Issue entitled
. Topics: Acoustic Stimulation; Auditory Cortex; Auditory Pathways; Auditory Threshold; Cochlear Implantation; Cochlear Implants; Cochlear Nerve; Electric Stimulation; Evoked Potentials, Auditory; Humans; Persons With Hearing Impairments; Prosthesis Design; Speech Perception; Time Factors
PubMed: 25445817
DOI: 10.1016/j.heares.2014.10.011 -
Journal of Neurophysiology Feb 2014Perceptual abnormalities such as hyperacusis and tinnitus often occur after acoustic overexposure. Although such exposure can also result in permanent threshold...
Perceptual abnormalities such as hyperacusis and tinnitus often occur after acoustic overexposure. Although such exposure can also result in permanent threshold elevation, some individuals with noise-induced hyperacusis or tinnitus show clinically normal thresholds. Recent work in animals has shown that a "neuropathic" noise exposure can cause immediate, permanent degeneration of the cochlear nerve despite complete threshold recovery and lack of hair cell damage (Kujawa SG, Liberman MC. J Neurosci 29: 14077-14085, 2009; Lin HW, Furman AC, Kujawa SG, Liberman MC. J Assoc Res Otolaryngol 12: 605-616, 2011). Here we ask whether this noise-induced primary neuronal degeneration results in abnormal auditory behavior, based on the acoustic startle response (ASR) and prepulse inhibition (PPI) of startle. Responses were measured in mice exposed either to a "neuropathic" noise or to a lower-intensity, "nonneuropathic" noise and in unexposed control mice. Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed control-like responses. Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies, inconsistent with the presence of tinnitus "filling in the gap." Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem. Considering the rapid postexposure onset of both cochlear neuropathy and exaggerated startle-based behavior, the results suggest a role for cochlear primary neuronal degeneration, per se, in the central neural excitability that could underlie the generation of hyperacusis.
Topics: Animals; Cell Death; Cochlear Nerve; Hyperacusis; Male; Mice; Mice, Inbred C57BL; Neurons; Noise; Sensory Gating; Tinnitus; Vestibulocochlear Nerve Diseases
PubMed: 24198321
DOI: 10.1152/jn.00184.2013 -
Proceedings of the National Academy of... Nov 2022Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide-frequency tuning. They are considered prime...
Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide-frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized in vivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from across-frequency coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of hot spot frequencies. A simple biophysical octopus cell model excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with the activation sequence of clustered excitatory inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.
Topics: Animals; Octopodiformes; Cochlear Nucleus; Cochlear Nerve; Cochlea; Mammals
PubMed: 36279465
DOI: 10.1073/pnas.2203748119