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Molecular and Cellular Neurosciences May 2022The vertebrate ear is endowed with remarkable perceptual capabilities. The faintest sounds produce vibrations of magnitudes comparable to those generated by thermal... (Review)
Review
The vertebrate ear is endowed with remarkable perceptual capabilities. The faintest sounds produce vibrations of magnitudes comparable to those generated by thermal noise and can nonetheless be detected through efficient amplification of small acoustic stimuli. Two mechanisms have been proposed to underlie such sound amplification in the mammalian cochlea: somatic electromotility and active hair-bundle motility. These biomechanical mechanisms may work in concert to tune auditory sensitivity. In addition to amplitude sensitivity, the hearing system shows exceptional frequency discrimination allowing mammals to distinguish complex sounds with great accuracy. For instance, although the wide hearing range of humans encompasses frequencies from 20 Hz to 20 kHz, our frequency resolution extends to one-thirtieth of the interval between successive keys on a piano. In this article, we review the different cochlear mechanisms underlying sound encoding in the auditory system, with a particular focus on the frequency decomposition of sounds. The relation between peak frequency of activation and location along the cochlea - known as tonotopy - arises from multiple gradients in biophysical properties of the sensory epithelium. Tonotopic mapping represents a major organizational principle both in the peripheral hearing system and in higher processing levels and permits the spectral decomposition of complex tones. The ribbon synapses connecting sensory hair cells to auditory afferents and the downstream spiral ganglion neurons are also tuned to process periodic stimuli according to their preferred frequency. Though sensory hair cells and neurons necessarily filter signals beyond a few kHz, many animals can hear well beyond this range. We finally describe how the cochlear structure shapes the neural code for further processing in order to send meaningful information to the brain. Both the phase-locked response of auditory nerve fibers and tonotopy are key to decode sound frequency information and place specific constraints on the downstream neuronal network.
Topics: Acoustic Stimulation; Animals; Cochlea; Hearing; Mammals; Neurons; Spiral Ganglion
PubMed: 35489636
DOI: 10.1016/j.mcn.2022.103732 -
Hearing Research Mar 2022Ultrastructural and molecular changes in the myelin of the cochlear nerve (CN) have been associated with decreased hearing-acuity with increasing age. But most of these...
Ultrastructural and molecular changes in the myelin of the cochlear nerve (CN) have been associated with decreased hearing-acuity with increasing age. But most of these are animal studies or with very few human samples. Hence, we studied the ultrastructure of the human CN at different ages. We obtained samples of CN from persons, who at the time of death belonged to young, middle or old age-groups; defined as ≤ 30, 31 to 50, and ≥ 51 years of age, respectively. These were processed for viewing under a transmission electron microscope (TEM). Morphology and morphometry were assessed after blinding the observer. Measurements of diameter (whole nerve fibre, axon), myelin thickness and calculation of G-ratio were made on calibrated images using ImageJ software. K-Means cluster analysis was performed based on total and inner nerve fibre area. Middle and old age CN showed degenerating axons, splitting of myelin sheath and myelin balloons. Between the middle and old age groups there was significant decrease in axon diameter (p<0.001), inner nerve fibre area (p<0.001), myelin thickness (p<0.001), nerve fibre diameter (p<0.001), and G-ratio (p<0.001). By clustering, we identified three distinct populations of myelinated nerve fibres: large, medium and small. The large fibres (by size), seen in the young, disappeared in the old age-group. We were unable to find any unmyelinated nerve fibres in this study. The morphological deterioration CN fibres may be a visible sign of molecular degeneration and contribute to decreased hearing-acuity.
Topics: Animals; Axons; Cochlear Nerve; Humans; Myelin Sheath; Nerve Fibers, Myelinated
PubMed: 35078131
DOI: 10.1016/j.heares.2022.108443 -
American Journal of Medical Genetics.... Apr 2021Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation and intellectual disability syndrome resulting from variants in DHCR7....
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation and intellectual disability syndrome resulting from variants in DHCR7. Auditory characteristics of persons with SLOS have been described in limited case reports but have not been systematically evaluated. The objective of this study is to describe the auditory phenotype in SLOS. Age- and ability-appropriate hearing evaluations were conducted on 32 patients with SLOS. A subset of 21 had auditory brainstem response testing, from which an auditory neural phenotype is described. Peripheral or retrocochlear auditory dysfunction was observed in at least one ear of 65.6% (21) of the patients in our SLOS cohort. The audiometric phenotype was heterogeneous and included conductive, mixed, and sensorineural hearing loss. The most common presentation was a slight to mild conductive hearing loss, although profound sensorineural hearing loss was also observed. Abnormal auditory brainstem responses indicative of retrocochlear dysfunction were identified in 21.9% of the patients. Many were difficult to test behaviorally and required objective assessment methods to estimate hearing sensitivity. Individuals with SLOS are likely to have hearing loss that may impact communication, including speech and language development. Routine audiologic surveillance should be conducted to ensure prompt management of hearing loss.
Topics: Adolescent; Adult; Audiometry; Auditory Diseases, Central; Child; Child, Preschool; Cochlear Nerve; Evoked Potentials, Auditory, Brain Stem; Female; Genetic Predisposition to Disease; Hearing Loss, Sensorineural; Humans; Infant; Male; Mutation; Oxidoreductases Acting on CH-CH Group Donors; Phenotype; Smith-Lemli-Opitz Syndrome; Young Adult
PubMed: 33529473
DOI: 10.1002/ajmg.a.62087 -
The Journal of Neuroscience : the... Jan 2020The activity of neurons is determined by the balance between their excitatory and inhibitory synaptic inputs. Neurons in the avian nucleus magnocellularis (NM) integrate...
The activity of neurons is determined by the balance between their excitatory and inhibitory synaptic inputs. Neurons in the avian nucleus magnocellularis (NM) integrate monosynaptic excitatory and polysynaptic inhibitory inputs from the auditory nerve, and transmit phase-locked output to higher auditory centers. The excitatory input is graded tonotopically, such that neurons tuned to higher frequency receive fewer, but larger, axon terminals. However, it remains unknown how the balance between excitatory and inhibitory inputs is determined in NM. We here examined synaptic and spike responses of NM neurons during stimulation of the auditory nerve in thick brain slices of chicken of both sexes, and found that the excitatory-inhibitory balance varied according to tonotopic region, ensuring reliable spike output across frequencies. Auditory nerve stimulation elicited IPSCs in NM neurons regardless of tonotopic region, but the dependence of IPSCs on intensity varied in a systematic way. In neurons tuned to low frequency, IPSCs appeared and increased in parallel with EPSCs with elevation of intensity, which expanded dynamic range by preventing saturation of spike generation. On the other hand, in neurons tuned to higher frequency, IPSCs were smaller than EPSCs and had higher thresholds for activation, thus facilitating high-fidelity transmission. Computer simulation confirmed that these differences in inhibitory input were optimally matched to the patterns of excitatory input, and enabled appropriate level of neuronal output for wide intensity and frequency ranges of sound in the auditory system. Neurons in nucleus magnocellularis encode timing information of sound across wide intensity ranges by integrating excitatory and inhibitory synaptic inputs from the auditory nerve, but underlying synaptic mechanisms of this integration are not fully understood. We here show that the excitatory-inhibitory relationship was expressed differentially at each tonotopic region; the relationship was linear in neurons tuned to low-frequency, expanding dynamic range by preventing saturation of spike generation; by contrast inhibitory input remained much smaller than excitatory input in neurons tuned to higher frequency, thus ensuring high-fidelity transmission. The tonotopic regulation of excitatory and inhibitory input optimized the output across frequencies and intensities, playing a fundamental role in the timing coding pathway in the auditory system.
Topics: Animals; Basal Nucleus of Meynert; Chickens; Cochlear Nerve; Computer Simulation; Electric Stimulation; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Female; Male; Neural Inhibition; Pitch Perception; Synapses; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 31727796
DOI: 10.1523/JNEUROSCI.1124-19.2019 -
Journal of the Association For Research... Dec 2022The middle-ear system relies on a balance of mass and stiffness characteristics for transmitting sound from the external environment to the cochlea and auditory neural...
The middle-ear system relies on a balance of mass and stiffness characteristics for transmitting sound from the external environment to the cochlea and auditory neural pathway. Phase is one aspect of sound that, when transmitted and encoded by both ears, contributes to binaural cue sensitivity and spatial hearing. The study aims were (i) to investigate the effects of middle-ear stiffness on the auditory brainstem neural encoding of phase in human adults with normal pure-tone thresholds and (ii) to investigate the relationships between middle-ear stiffness-induced changes in wideband acoustic immittance and neural encoding of phase. The auditory brainstem neural encoding of phase was measured using the auditory steady-state response (ASSR) with and without middle-ear stiffness elicited via contralateral activation of the middle-ear muscle reflex (MEMR). Middle-ear stiffness was quantified using a wideband acoustic immittance assay of acoustic absorbance. Statistical analyses demonstrated decreased ASSR phase lag and decreased acoustic absorbance with contralateral activation of the MEMR, consistent with increased middle-ear stiffness changing the auditory brainstem neural encoding of phase. There were no statistically significant correlations between stiffness-induced changes in wideband acoustic absorbance and ASSR phase. The findings of this study may have important implications for understanding binaural cue sensitivity and horizontal plane sound localization in audiologic and otologic clinical populations that demonstrate changes in middle-ear stiffness, including cochlear implant recipients who use combined electric and binaural acoustic hearing and otosclerosis patients.
Topics: Adult; Humans; Ear, Middle; Hearing Tests; Hearing; Cochlear Nerve; Brain Stem; Auditory Threshold; Acoustic Stimulation
PubMed: 36214911
DOI: 10.1007/s10162-022-00872-0 -
Frontiers in Immunology 2022Human inner ear contains macrophages whose functional role in early development is yet unclear. Recent studies describe inner ear macrophages act as effector cells of...
BACKGROUND
Human inner ear contains macrophages whose functional role in early development is yet unclear. Recent studies describe inner ear macrophages act as effector cells of the innate immune system and are often activated following acoustic trauma or exposure to ototoxic drugs. Few or limited literature describing the role of macrophages during inner ear development and organogenesis.
MATERIAL AND METHODS
We performed a study combining immunohistochemistry and immunofluorescence using antibodies against IBA1, CX3CL1, CD168, CD68, CD45 and CollagenIV. Immune staining and quantification was performed on human embryonic inner ear sections from gestational week 09 to 17.
RESULTS
The study showed IBA1 and CD45 positive cells in the mesenchymal tissue at GW 09 to GW17. No IBA1 positive macrophages were detected in the sensory epithelium of the cochlea and vestibulum. Fractalkine (CX3CL1) signalling was initiated GW10 and parallel chemotactic attraction and migration of macrophages into the inner ear. Macrophages also migrated into the spiral ganglion, cochlear nerve, and peripheral nerve fibers and tissue-expressing CX3CL1. The mesenchymal tissue at all gestational weeks expressed CD163 and CD68.
CONCLUSION
Expressions of markers for resident and non-resident macrophages (IBA1, CD45, CD68, and CD163) were identified in the human fetal inner ear. We speculate that these cells play a role for the development of human inner ear tissue including shaping of the gracile structures.
Topics: Chemokine CX3CL1; Cochlea; Ear, Inner; Humans; Macrophages; Spiral Ganglion
PubMed: 36159857
DOI: 10.3389/fimmu.2022.965196 -
Otology & Neurotology : Official... Jan 2022We aimed to investigate the clinical features of cochlear nerve deficiency (CND), and in particular, the long-term course of hearing disability and audiogram shapes. (Observational Study)
Observational Study
OBJECTIVE
We aimed to investigate the clinical features of cochlear nerve deficiency (CND), and in particular, the long-term course of hearing disability and audiogram shapes.
STUDY DESIGN
Retrospective observational nonrandomized group study.
SETTING
Academic medical center.
PATIENTS/INTERVENTIONS
The subjects were 63 children with congenital hearing loss who visited our hospital between 2009 and 2019 and underwent MRI, based on which they were diagnosed with CND. There were 61 cases of unilateral CND and two cases of bilateral CND.
MAIN OUTCOME MEASURES
Imaging tests by MRI and CT and audiometric assessments by pure-tone audiometry and distortion product otoacoustic emission were performed.
RESULTS
Among the cases of CND diagnosed by assessing the cochlear nerve on MRI, approximately 20% of the bony cochlear nerve canals that could be assessed on CT were normal. Of the 61 cases diagnosed with unilateral CND, 55 cases had cochlear nerve aplasia (90.2%), and six had cochlear nerve hypoplasia (9.8%), with a mean hearing ability of 92.2 and 94.6 dB HL, respectively. Thus, the majority of cases had severe-to-profound hearing loss. The overall audiometric patterns were 78.7% flat, 9.8% cookie-bite, and 9.8% high-frequency. Six of 61 cases (9.8%) had a distortion product otoacoustic emission (DPOAE) response based on the affected side, and none of the cases lost the response during follow-up.
CONCLUSIONS
Herein, we report the largest study on CND and performed CND image and audiometric assessments. Accurately in diagnosing CND requires not only CT but also MRI assessment. Hearing loss is often severe to profound; however, various audiometric patterns have been observed. CND includes a small number of cases that respond to DPOAE, indicating that some CND cases are clinically diagnosed with auditory neuropathy spectrum disorder (ANSD). A sustained DPOAE response might help in differentiating CND from other ANSDs. Children with congenital deafness who have passed the newborn hearing screening by DPOAE should be examined by MRI to rule out CND.
Topics: Audiometry, Pure-Tone; Child; Cochlear Nerve; Hearing Loss; Hearing Loss, Central; Hearing Loss, Sensorineural; Humans; Infant, Newborn; Otoacoustic Emissions, Spontaneous; Retrospective Studies
PubMed: 34538855
DOI: 10.1097/MAO.0000000000003365 -
Biomedical Engineering Online Jan 2021An electrical potential not previously reported-electrical cochlear response (ECR)-observed only in implanted patients is described. Its amplitude and growth slope are a...
BACKGROUND
An electrical potential not previously reported-electrical cochlear response (ECR)-observed only in implanted patients is described. Its amplitude and growth slope are a measurement of the stimulation achieved by a tone pip on the auditory nerve. The stimulation and recording system constructed for this purpose, the features of this potential obtained in a group of 43 children, and its possible clinical use are described. The ECR is obtained by averaging the EEG epochs acquired each time the cochlear implant (CI) processes a tone pip of known frequency and intensity when the patient is sleeping and using the CI in everyday mode. The ECR is sensitive to tone pip intensity level, microphone sensitivity, sound processor gain, dynamic range of electrical current, and responsiveness to electrical current of the auditory nerve portion involved with the electrode under test. It allows individual evaluation of intracochlear electrodes by choosing, one at the time, the central frequency of the electrode as the test tone pip frequency, so the ECR measurement due to a variable intensity tone pip allows to establish the suitability of the dynamic range of the electrode current.
RESULTS
There is a difference in ECR measurements when patients are grouped based on their auditory behavior. The ECR slope and amplitude for the Sensitive group is 0.2 μV/dB and 10 μV at 50 dB compared with 0.04 μV/dB and 3 μV at 50dB for the Inconsistent group. The clinical cases show that adjusting the dynamic range of current based on the ECR improved the patient's auditory behavior.
CONCLUSIONS
ECR can be recorded regardless of the artifact due to the electromyographic activity of the patient and the functioning of the CI. Its amplitude and growth slope versus the intensity of the stimulus differs between electrodes. The relationship between minimum ECR detection intensity level and auditory threshold suggests the possibility of estimating patient auditory thresholds this way. ECR does not depend on the subject's age, cooperation, or health status. It can be obtained at any time after implant surgery and the test procedure is the same regardless of device manufacturer.
Topics: Auditory Threshold; Child; Cochlear Implants; Cochlear Nerve; Evoked Potentials, Auditory; Female; Humans; Male
PubMed: 33446195
DOI: 10.1186/s12938-020-00844-6 -
Molecular and Cellular Neurosciences Jan 2022Afferent innervation of the cochlea by the auditory nerve declines during aging and potentially after sound overexposure, producing the common pathology known as... (Review)
Review
Afferent innervation of the cochlea by the auditory nerve declines during aging and potentially after sound overexposure, producing the common pathology known as cochlear synaptopathy. Auditory-nerve-fiber loss is difficult to detect with the clinical audiogram and has been proposed to cause 'hidden hearing loss' including impaired speech-in-noise perception. While evidence that auditory-nerve-fiber loss causes hidden hearing loss in humans is controversial, behavioral animal models hold promise to rigorously test this hypothesis because neural lesions can be induced and histologically validated. Here, we review recent animal behavioral studies on the impact of auditory-nerve-fiber loss on perception in a range of species. We first consider studies of tinnitus and hyperacusis inferred from acoustic startle reflexes, followed by a review of operant-conditioning studies of the audiogram, temporal integration for tones of varying duration, temporal resolution of gaps in noise, and tone-in-noise detection. Studies quantifying the audiogram show that tone-in-quiet sensitivity is unaffected by auditory-nerve-fiber loss unless neural lesions exceed 80%, at which point large deficits are possible. Changes in other aspects of perception, which were typically investigated for moderate-to-severe auditory-nerve-fiber loss of 50-70%, appear heterogeneous across studies and might be small compared to impairment caused by hair-cell pathologies. Future studies should pursue recent findings that behavioral sensitivity to brief tones and silent gaps in noise may be particularly vulnerable to auditory-nerve-fiber loss. Furthermore, aspects of auditory perception linked to central inhibition and fine neural response timing, such as modulation masking release and spatial hearing, may be productive directions for further animal behavioral research.
Topics: Animals; Auditory Perception; Auditory Threshold; Cochlear Nerve; Evoked Potentials, Auditory, Brain Stem; Hearing Loss; Models, Animal
PubMed: 34883241
DOI: 10.1016/j.mcn.2021.103692 -
American Journal of Physiology. Cell... Oct 2022Sound is converted by hair cells in the cochlea into electrical signals, which are transmitted by spiral ganglion neurons (SGNs) and heard by the auditory cortex. G... (Review)
Review
Sound is converted by hair cells in the cochlea into electrical signals, which are transmitted by spiral ganglion neurons (SGNs) and heard by the auditory cortex. G protein-coupled receptors (GPCRs) are crucial receptors that regulate a wide range of physiological functions in different organ and tissues. The research of GPCRs in the cochlea is essential for the understanding of the cochlea development, hearing disorders, and the treatment for hearing loss. Recently, several GPCRs have been found to play important roles in the cochlea. Frizzleds and Lgrs are dominant GPCRs that regulate stem cell self-renew abilities. Moreover, Frizzleds and Celsrs have been demonstrated to play core roles in the modulation of cochlear planar cell polarity (PCP). In addition, hearing loss can be caused by mutations of certain GPCRs, such as Vlgr1, Gpr156, S1P2, and Gpr126. And A1, A2A, and CB2 activation by agonists has protective functions on noise- or drug-induced hearing loss. Here, we review the key findings of GPCR in the cochlea and discuss the role of GPCR in the cochlea, such as stem cell fate, PCP, hearing loss, and hearing protection.
Topics: Cell Polarity; Cochlea; Hearing; Receptors, G-Protein-Coupled; Spiral Ganglion
PubMed: 35938679
DOI: 10.1152/ajpcell.00453.2021