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Hearing Research Jul 2018CaBPs are a family of Ca binding proteins related to calmodulin. Two CaBP family members, CaBP1 and CaBP2, are highly expressed in the cochlea. Here, we investigated the...
CaBPs are a family of Ca binding proteins related to calmodulin. Two CaBP family members, CaBP1 and CaBP2, are highly expressed in the cochlea. Here, we investigated the significance of CaBP1 and CaBP2 for hearing in mice lacking expression of these proteins (CaBP1 KO and CaBP2 KO) using auditory brain responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In CaBP1 KO mice, ABR wave I was larger in amplitude, and shorter in latency and faster in decay, suggestive of enhanced synchrony of auditory nerve fibers. This interpretation was supported by the greater excitability of CaBP1 KO than WT neurons in whole-cell patch clamp recordings of spiral ganglion neurons in culture, and normal presynaptic function of CaBP1 KO IHCs. DPOAEs and ABR thresholds were normal in 4-week old CaBP1 KO mice, but elevated ABR thresholds became evident at 32 kHz at 9 weeks, and at 8 and 16 kHz by 6 months of age. In contrast, CaBP2 KO mice exhibited significant ABR threshold elevations at 4 weeks of age that became more severe in the mid-frequency range by 9 weeks. Though normal at 4 weeks, DPOAEs in CaBP2 KO mice were significantly reduced in the mid-frequency range by 9 weeks. Our results reveal requirements for CaBP1 and CaBP2 in the peripheral auditory system and highlight the diverse modes by which CaBPs influence sensory processing.
Topics: Acoustic Stimulation; Age Factors; Animals; Auditory Pathways; Auditory Threshold; Calcium-Binding Proteins; Cells, Cultured; Cochlear Nerve; Evoked Potentials, Auditory, Brain Stem; Female; Hair Cells, Auditory; Hearing Loss; Male; Mice, Inbred C57BL; Mice, Knockout; Otoacoustic Emissions, Spontaneous; Reaction Time; Spiral Ganglion; Synaptic Potentials; Synaptic Transmission; Time Factors
PubMed: 29661613
DOI: 10.1016/j.heares.2018.04.001 -
Journal of Neurophysiology Mar 2021The configuration of lizard ears, where sound can reach both surfaces of the eardrums, produces a strongly directional ear, but the subsequent processing of sound...
The configuration of lizard ears, where sound can reach both surfaces of the eardrums, produces a strongly directional ear, but the subsequent processing of sound direction by the auditory pathway is unknown. We report here on directional responses from the first stage, the auditory nerve. We used laser vibrometry to measure eardrum responses in Tokay geckos and in the same animals recorded 117 auditory nerve single fiber responses to free-field sound from radially distributed speakers. Responses from all fibers showed strongly lateralized activity at all frequencies, with an ovoidal directivity that resembled the eardrum directivity. Geckos are vocal and showed pronounced nerve fiber directionality to components of the call. To estimate the accuracy with which a gecko could discriminate between sound sources, we computed the Fisher information (FI) for each neuron. FI was highest just contralateral to the midline, front and back. Thus, the auditory nerve could provide a population code for sound source direction, and geckos should have a high capacity to differentiate between midline sound sources. In brain, binaural comparisons, for example, by IE (ipsilateral excitatory, contralateral inhibitory) neurons, should sharpen the lateralized responses and extend the dynamic range of directionality. In mammals, the two ears are unconnected pressure receivers, and sound direction is computed from binaural interactions in the brain, but in lizards, the eardrums interact acoustically, producing a strongly directional response. We show strongly lateralized responses from gecko auditory nerve fibers to directional sound stimulation and high Fisher information on either side of the midline. Thus, already the auditory nerve provides a population code for sound source direction in the gecko.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Cochlear Nerve; Female; Lizards; Male; Sound Localization; Vibration
PubMed: 33534648
DOI: 10.1152/jn.00576.2020 -
Expert Opinion on Biological Therapy Jan 2013In the auditory system, a specialized subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with... (Review)
Review
INTRODUCTION
In the auditory system, a specialized subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with severe-to-profound sensorineural hearing impairment these sensory auditory neurons can be directly stimulated by a cochlear implant, which restores sound input to the brainstem after the loss of hair cells. This neural prosthesis therefore depends on a residual population of functional neurons in order to function effectively.
AREAS COVERED
In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, the benefits derived from a cochlear implant may be minimal. One way in which to restore function to the auditory nerve is to replace these lost neurons using differentiated stem cells, thus re-establishing the neural circuit required for cochlear implant function. Such a therapy relies on producing an appropriate population of electrophysiologically functional neurons from stem cells, and on these cells integrating and reconnecting in an appropriate manner in the deaf cochlea.
EXPERT OPINION
Here we review progress in the field to date, including some of the key functional features that stem cell-derived neurons would need to possess and how these might be enhanced using electrical stimulation from a cochlear implant.
Topics: Cell Differentiation; Cochlear Implants; Cochlear Nerve; Embryonic Stem Cells; Humans; Stem Cell Transplantation
PubMed: 23094991
DOI: 10.1517/14712598.2013.728583 -
Hearing Research May 2023Computational models are useful tools to investigate scientific questions that would be complicated to address using an experimental approach. In the context of...
Computational models are useful tools to investigate scientific questions that would be complicated to address using an experimental approach. In the context of cochlear-implants (CIs), being able to simulate the neural activity evoked by these devices could help in understanding their limitations to provide natural hearing. Here, we present a computational modelling framework to quantify the transmission of information from sound to spikes in the auditory nerve of a CI user. The framework includes a model to simulate the electrical current waveform sensed by each auditory nerve fiber (electrode-neuron interface), followed by a model to simulate the timing at which a nerve fiber spikes in response to a current waveform (auditory nerve fiber model). Information theory is then applied to determine the amount of information transmitted from a suitable reference signal (e.g., the acoustic stimulus) to a simulated population of auditory nerve fibers. As a use case example, the framework is applied to simulate published data on modulation detection by CI users obtained using direct stimulation via a single electrode. Current spread as well as the number of fibers were varied independently to illustrate the framework capabilities. Simulations reasonably matched experimental data and suggested that the encoded modulation information is proportional to the total neural response. They also suggested that amplitude modulation is well encoded in the auditory nerve for modulation rates up to 1000 Hz and that the variability in modulation sensitivity across CI users is partly because different CI users use different references for detecting modulation.
Topics: Cochlear Implants; Cochlear Implantation; Acoustic Stimulation; Cochlear Nerve; Computer Simulation; Electric Stimulation; Evoked Potentials, Auditory
PubMed: 37004271
DOI: 10.1016/j.heares.2023.108744 -
Nature Communications Nov 2021The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its...
The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Brain Stem; Cochlear Nerve; Mice; Mice, Inbred C57BL; Reflex, Startle
PubMed: 34737329
DOI: 10.1038/s41467-021-26723-9 -
Journal of the Association For Research... Apr 2023Two EEG experiments measured the sustained neural response to amplitude-modulated (AM) high-rate pulse trains presented to a single cochlear-implant (CI) electrode....
Two EEG experiments measured the sustained neural response to amplitude-modulated (AM) high-rate pulse trains presented to a single cochlear-implant (CI) electrode. Stimuli consisted of two interleaved pulse trains with AM rates F1 and F2 close to 80 and 120 Hz respectively, and where F2 = 1.5F1. Following Carlyon et al. (J Assoc Res Otolaryngol, 2021), we assume that such stimuli can produce a neural distortion response (NDR) at F0 = F2-F1 Hz if temporal dependencies ("smoothing") in the auditory system are followed by one or more neural nonlinearities. In experiment 1, the rate of each pulse train was 480 pps and the gap between pulses in the F1 and F2 pulse trains ranged from 0 to 984 µs. The NDR had a roughly constant amplitude for gaps between 0 and about 200-400 µs, and decreased for longer gaps. We argue that this result is consistent with a temporal dependency, such as facilitation, operating at the level of the auditory nerve and/or with co-incidence detection by cochlear-nucleus neurons. Experiment 2 first measured the NDR for stimuli at each listener's most comfortable level ("MCL") and for F0 = 37, 40, and 43 Hz. This revealed a group delay of about 42 ms, consistent with a thalamic/cortical source. We then showed that the NDR grew steeply with stimulus amplitude and, for most listeners, decreased by more than 12 dB between MCL and 75% of the listener's dynamic range. We argue that the NDR is a potentially useful objective estimate of MCL.
Topics: Cochlear Implants; Cochlear Implantation; Cochlear Nerve; Electrodes, Implanted; Electric Stimulation; Electroencephalography
PubMed: 36754938
DOI: 10.1007/s10162-023-00886-2 -
Acta Neurochirurgica Jul 2017To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal...
Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach: planned subtotal resection followed by gamma knife radiosurgery.
OBJECTIVE
To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves.
METHODS
Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up.
RESULTS
A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4-78). Mean presurgical tumor volume was 12.5 cm (range 1.47-34.9). Postoperative status showed normal facial nerve function (House-Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner-Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8-13.9). Mean tumor volume at GKRS was 3.5 cm (range 0.5-12.8), corresponding to mean residual volume of 29.4% (range 6-46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11-12). Mean follow-up after GKRS was 24 months (range 3-60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time.
CONCLUSION
Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.
Topics: Adult; Aged; Cochlear Nerve; Facial Nerve; Female; Hearing; Humans; Male; Middle Aged; Neuroma, Acoustic; Postoperative Complications; Radiosurgery
PubMed: 28516364
DOI: 10.1007/s00701-017-3194-0 -
Hearing Research Mar 2019Auditory-nerve fibers are lost steadily with age and as a possible consequence of noise-induced glutamate excitotoxicity. Auditory-nerve loss in the absence of other...
Auditory-nerve fibers are lost steadily with age and as a possible consequence of noise-induced glutamate excitotoxicity. Auditory-nerve loss in the absence of other cochlear pathologies is thought to be undetectable with a pure-tone audiogram while degrading real-world speech perception (hidden hearing loss). Perceptual deficits remain unclear, however, due in part to the limited behavioral capacity of existing rodent models to discriminate complex sounds. The budgerigar is an avian vocal learner with human-like behavioral sensitivity to many simple and complex sounds and the capacity to mimic speech. Previous studies in this species show that intracochlear kainic-acid infusion reduces wave 1 of the auditory brainstem response by 40-70%, consistent with substantial excitotoxic auditory-nerve damage. The present study used operant-conditioning procedures in trained budgerigars to quantify kainic-acid effects on tone detection across frequency (0.25-8 kHz; the audiogram) and as a function of duration (20-160 ms; temporal integration). Tone thresholds in control animals were lowest from 1 to 4 kHz and decreased with increasing duration as in previous studies of the budgerigar. Behavioral results in kainic-acid-exposed animals were as sensitive as in controls, suggesting preservation of the audiogram and temporal integration despite auditory-nerve loss associated with up to 70% wave 1 reduction. Distortion-product otoacoustic emissions were also preserved in kainic-acid exposed animals, consistent with normal hair-cell function. These results highlight considerable perceptual resistance of tone-detection performance with selective auditory-nerve loss. Future behavioral studies in budgerigars with auditory-nerve damage can use complex speech-like stimuli to help clarify aspects of auditory perception impacted by this common cochlear pathology.
Topics: Acoustic Stimulation; Animals; Audiometry, Pure-Tone; Auditory Perception; Auditory Threshold; Behavior, Animal; Cochlear Nerve; Conditioning, Operant; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem; Female; Humans; Kainic Acid; Male; Melopsittacus; Otoacoustic Emissions, Spontaneous; Ototoxicity; Psychoacoustics
PubMed: 30703625
DOI: 10.1016/j.heares.2019.01.019 -
The Journal of Neuroscience : the... Mar 2022Abnormal levels of acoustic activity can result in hearing problems such as tinnitus and language processing disorders, but the underlying cellular and synaptic changes...
Abnormal levels of acoustic activity can result in hearing problems such as tinnitus and language processing disorders, but the underlying cellular and synaptic changes triggered by abnormal activity are not well understood. To address this issue, we studied the time course of activity-dependent changes that occur at auditory nerve synapses in mice of both sexes after noise exposure and conductive hearing loss. We found that EPSC amplitude and synaptic depression decreased within 2 d of noise exposure through a decrease in the probability of vesicle release (). This was followed by a gradual increase in EPSC amplitude through a larger pool of releasable vesicles (). Occlusion of the ear canal led to a rapid decrease in EPSC amplitude through a decrease in , which was followed by an increase in EPSC amplitude and synaptic depression through an increase in After returning to normal sound levels, synaptic depression recovered to control levels within 1-2 d. However, repeated exposure to noise for as little as 8 h/d caused synaptic changes after 7 d, suggesting recovery did not fully offset changes. Thus, there appear to be three activity-dependent mechanisms in auditory nerve synapses-bidirectional changes in in 1-2 d, slower bidirectional changes in through synaptic growth or retraction, and rapid downregulation of with low activity. The dynamic changes indicate that multiple mechanisms are present to fine-tune synaptic fidelity across different acoustic conditions in a simple relay. Hearing impairments can arise from exposure to noise or conductive hearing loss. This appears to result from changes in the brain, but the mechanisms are not well understood. We study this issue by studying the synapses made by auditory nerve fibers called endbulbs of Held. These synapses undergo bidirectional changes in size and release probability of neurotransmitter in response to increased or decreased activity. Here, we made a close examination of how quickly these synaptic characteristics change, which indicates there are at least three cellular mechanisms underlying changes. Furthermore, repeated exposure to brief periods of noise can produce cumulative effects. These changes could significantly affect hearing, especially because they occur at the start of the central auditory pathway.
Topics: Animals; Auditory Pathways; Cochlear Nerve; Female; Hearing Loss, Conductive; Male; Mice; Noise; Synapses
PubMed: 35181597
DOI: 10.1523/JNEUROSCI.1583-21.2022 -
Journal of the Association For Research... Feb 2021Variations in neural health along the cochlea can degrade the spectral and temporal representation of sounds conveyed by cochlear implants (CIs). We evaluated and...
Variations in neural health along the cochlea can degrade the spectral and temporal representation of sounds conveyed by cochlear implants (CIs). We evaluated and compared one electrophysiological measure and two behavioural measures that have been proposed as estimates of neural health patterns, in order to explore the extent to which the different measures provide converging and consistent neural health estimates. All measures were obtained from the same 11 users of the Cochlear Corporation CI. The two behavioural measures were multipulse integration (MPI) and the polarity effect (PE), both measured on each of seven electrodes per subject. MPI was measured as the difference between thresholds at 80 pps and 1000 pps, and PE as the difference in thresholds between cathodic- and anodic-centred quadraphasic (QP) 80-pps pulse trains. It has been proposed that good neural health corresponds to a large MPI and to a large negative PE (lower thresholds for cathodic than anodic pulses). The electrophysiological measure was the effect of interphase gap (IPG) on the offset of the ECAP amplitude growth function (AGF), which has been correlated with spiral ganglion neuron density in guinea pigs. This 'IPG offset' was obtained on the same subset of electrodes used for the behavioural measures. Despite high test-retest reliability, there were no significant correlations between the neural health estimates for either within-subject comparisons across the electrode array, or between-subject comparisons of the means. A phenomenological model of a population of spiral ganglion neurons was then used to investigate physiological mechanisms that might underlie the different neural health estimates. The combined experimental and modelling results provide evidence that PE, MPI and IPG offset may reflect different characteristics of the electrode-neural interface.
Topics: Animals; Auditory Perception; Cochlear Implants; Cochlear Nerve; Computer Simulation; Guinea Pigs; Reproducibility of Results
PubMed: 33150541
DOI: 10.1007/s10162-020-00773-0