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The Journal of Neuroscience : the... Mar 2023Resident cochlear macrophages rapidly migrate into the inner hair cell synaptic region and directly contact the damaged synaptic connections after noise-induced...
Resident cochlear macrophages rapidly migrate into the inner hair cell synaptic region and directly contact the damaged synaptic connections after noise-induced synaptopathy. Eventually, such damaged synapses are spontaneously repaired, but the precise role of macrophages in synaptic degeneration and repair remains unknown. To address this, cochlear macrophages were eliminated using colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Sustained treatment with PLX5622 in mice of both sexes led to robust elimination of resident macrophages (∼94%) without significant adverse effects on peripheral leukocytes, cochlear function, and structure. At 1 day (d) post noise exposure of 93 or 90 dB SPL for 2 hours, the degree of hearing loss and synapse loss were comparable in the presence and absence of macrophages. At 30 d after exposure, damaged synapses appeared repaired in the presence of macrophages. However, in the absence of macrophages, such synaptic repair was significantly reduced. Remarkably, on cessation of PLX5622 treatment, macrophages repopulated the cochlea, leading to enhanced synaptic repair. Elevated auditory brainstem response thresholds and reduced auditory brainstem response Peak 1 amplitudes showed limited recovery in the absence of macrophages but recovered similarly with resident and repopulated macrophages. Cochlear neuron loss was augmented in the absence of macrophages but showed preservation with resident and repopulated macrophages after noise exposure. While the central auditory effects of PLX5622 treatment and microglia depletion remain to be investigated, these data demonstrate that macrophages do not affect synaptic degeneration but are necessary and sufficient to restore cochlear synapses and function after noise-induced synaptopathy. The synaptic connections between cochlear inner hair cells and spiral ganglion neurons can be lost because of noise over exposure or biological aging. This loss may represent the most common causes of sensorineural hearing loss also known as hidden hearing loss. Synaptic loss results in degradation of auditory information, leading to difficulty in listening in noisy environments and other auditory perceptual disorders. We demonstrate that resident macrophages of the cochlea are necessary and sufficient to restore synapses and function following synaptopathic noise exposure. Our work reveals a novel role for innate-immune cells, such as macrophages in synaptic repair, that could be harnessed to regenerate lost ribbon synapses in noise- or age-linked cochlear synaptopathy, hidden hearing loss, and associated perceptual anomalies.
Topics: Male; Female; Animals; Mice; Hair Cells, Auditory, Inner; Hearing Loss, Noise-Induced; Acoustic Stimulation; Auditory Threshold; Cochlea; Synapses; Evoked Potentials, Auditory, Brain Stem; Macrophages
PubMed: 36810227
DOI: 10.1523/JNEUROSCI.1273-22.2023 -
Scientific Reports Nov 2023Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has...
Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has been extensively studied by confocal microscopy, however, understanding the nature and sequence of damage requires ultrastructural analysis. Here, we used focused ion-beam scanning electron microscopy to mill, image, segment and reconstruct ANF terminals in mice, 1 day and 1 week after synaptopathic exposure (8-16 kHz, 98 dB SPL). At both survivals, ANF terminals were normal in number, but 62% and 53%, respectively, lacked normal synaptic specializations. Most non-synapsing fibers (57% and 48% at 1 day and 1 week) remained in contact with an IHC and contained healthy-looking organelles. ANFs showed a transient increase in mitochondrial content (51%) and efferent innervation (34%) at 1 day. Fibers maintaining synaptic connections showed hypertrophy of pre-synaptic ribbons at both 1 day and 1 week. Non-synaptic fibers were lower in mitochondrial content and typically on the modiolar side of the IHC, where ANFs with high-thresholds and low spontaneous rates are normally found. Even 1 week post-exposure, many ANF terminals remained in IHC contact despite loss of synaptic specializations, thus, regeneration efforts at early post-exposure times should concentrate on synaptogenesis rather than neurite extension.
Topics: Mice; Animals; Cochlea; Noise; Hearing Loss, Noise-Induced; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Synapses; Cochlear Nerve; Auditory Threshold
PubMed: 37945811
DOI: 10.1038/s41598-023-46859-6 -
Hearing Research Apr 2016Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as... (Review)
Review
Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as tinnitus is often associated with hearing impairment, it is unclear how a decrease of afferent drive can result in central hyperactivity. In this review, we first assess methods for tinnitus induction and objective measures of the tinnitus percept in animal models. From animal studies, we discuss evidence that tinnitus originates in the cochlear nucleus (CN), and hypothesize mechanisms whereby hyperactivity may develop in the CN after peripheral auditory nerve damage. We elaborate how this process is likely mediated by plasticity of auditory-somatosensory integration in the CN: the circuitry in normal circumstances maintains a balance of auditory and somatosensory activities, and loss of auditory inputs alters the balance of auditory somatosensory integration in a stimulus timing dependent manner, which propels the circuit towards hyperactivity. Understanding the mechanisms underlying tinnitus generation is essential for its prevention and treatment. This article is part of a Special Issue entitled
. Topics: Acoustic Stimulation; Animals; Auditory Pathways; Auditory Perception; Auditory Threshold; Cochlear Nucleus; Evoked Potentials, Auditory, Brain Stem; Humans; Inferior Colliculi; Neuronal Plasticity; Somatosensory Cortex; Tinnitus
PubMed: 26074307
DOI: 10.1016/j.heares.2015.06.005 -
Trends in Hearing 2022Most human auditory psychophysics research has historically been conducted in carefully controlled environments with calibrated audio equipment, and over potentially...
Most human auditory psychophysics research has historically been conducted in carefully controlled environments with calibrated audio equipment, and over potentially hours of repetitive testing with expert listeners. Here, we operationally define such conditions as having high 'auditory hygiene'. From this perspective, conducting auditory psychophysical paradigms online presents a serious challenge, in that results may hinge on absolute sound presentation level, reliably estimated perceptual thresholds, low and controlled background noise levels, and sustained motivation and attention. We introduce a set of procedures that address these challenges and facilitate auditory hygiene for online auditory psychophysics. First, we establish a simple means of setting sound presentation levels. Across a set of four level-setting conditions conducted in person, we demonstrate the stability and robustness of this level setting procedure in open air and controlled settings. Second, we test participants' tone-in-noise thresholds using widely adopted online experiment platforms and demonstrate that reliable threshold estimates can be derived online in approximately one minute of testing. Third, using these level and threshold setting procedures to establish participant-specific stimulus conditions, we show that an online implementation of the classic probe-signal paradigm can be used to demonstrate frequency-selective attention on an individual-participant basis, using a third of the trials used in recent in-lab experiments. Finally, we show how threshold and attentional measures relate to well-validated assays of online participants' in-task motivation, fatigue, and confidence. This demonstrates the promise of online auditory psychophysics for addressing new auditory perception and neuroscience questions quickly, efficiently, and with more diverse samples. Code for the tests is publicly available through Pavlovia and Gorilla.
Topics: Auditory Perception; Auditory Threshold; Humans; Noise; Psychophysics
PubMed: 36131515
DOI: 10.1177/23312165221118792 -
CoDAS 2023To identify the pathophysiological definitions adopted by studies investigating "cochlear synaptopathy" (CS) and "hidden hearing loss" (HHL). (Review)
Review
PURPOSE
To identify the pathophysiological definitions adopted by studies investigating "cochlear synaptopathy" (CS) and "hidden hearing loss" (HHL).
RESEARCH STRATEGIES
The combination of keywords "Auditory Synaptopathy" or "Neuronal Synaptopathy" or "Hidden Hearing Loss" with "etiology" or "causality" or "diagnosis" was used in the databases EMBASE, Pubmed (MEDLINE), CINAHL (EBSCO), and Web of Science.
SELECTION CRITERIA
Studies that investigated CS or HHL in humans using behavioral and/or electrophysiological procedures were included.
DATA ANALYSIS
Data analysis and extraction were performed with regard to terminology, definitions, and population.
RESULTS
49 articles were included. Of these, 61.2% used the CS terminology, 34.7% used both terms, and 4.1% used HHL. The most-studied conditions were exposure to noise and tinnitus.
CONCLUSION
CS terminology was used in most studies, referring to the pathophysiological process of deafferentiation between the cochlear nerve fibers and inner hair cells.
Topics: Humans; Hearing Loss, Noise-Induced; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Cochlea; Noise; Deafness
PubMed: 37991055
DOI: 10.1590/2317-1782/20232023032pt -
Fa Yi Xue Za Zhi Aug 2023The qualitative, quantitative, and localization analysis of hearing loss is one of the important contents of forensic clinical research and identification. Pure-tone... (Review)
Review
The qualitative, quantitative, and localization analysis of hearing loss is one of the important contents of forensic clinical research and identification. Pure-tone audiometry is the "gold standard" for hearing loss assessment, but it is affected by the subjective cooperation of the assessed person. Due to the complexity of the auditory pathway and the diversity of hearing loss, the assessment of hearing loss requires the combination of various subjective and objective audiometric techniques, along with comprehensive evaluation based on the case situation, clinical symptoms, and other examinations to ensure the scientificity, accuracy and reliability of forensic hearing impairment assessment. Objective audiometry includes acoustic impedance, otoacoustic emission, and various auditory evoked potentials. The frequency-specific auditory brainstem response (ABR), 40 Hz auditory event related potential, and auditory steady-state response are commonly used for objective hearing threshold assessment. The combined application of acoustic impedance, otoacoustic emission and ABR can be used to locate hearing loss and determine whether it is located in the middle ear, cochlea, or posterior cochlea. This article reviews the application value of objective audiometry techniques in hearing threshold assessment and hearing loss localization, aiming to provide reference for forensic identification of hearing loss.
Topics: Humans; Reproducibility of Results; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Hearing Loss; Audiometry, Pure-Tone; Clinical Medicine
PubMed: 37859474
DOI: 10.12116/j.issn.1004-5619.2023.230406 -
Neuroscience May 2019Noise-induced hidden hearing loss (NIHHL) has attracted great attention in hearing research and clinical audiology since the discovery of significant noise-induced... (Review)
Review
Noise-induced hidden hearing loss (NIHHL) has attracted great attention in hearing research and clinical audiology since the discovery of significant noise-induced synaptic damage in the absence of permanent threshold shifts (PTS) in animal models. Although the extant evidence for this damage is based on animal models, NIHHL likely occurs in humans as well. This review focuses on three issues concerning NIHHL that are somewhat controversial: (1) whether disrupted synapses can be re-established; (2) whether synaptic damage and repair are responsible for the initial temporal threshold shifts (TTS) and subsequent recovery; and (3) the relationship between the synaptic damage and repair processes and neural coding deficits. We conclude that, after a single, brief noise exposure, (1) the damaged and the totally destroyed synapses can be partially repaired, but the repaired synapses are functionally abnormal; (2) While deficits are observed in some aspects of neural responses related to temporal and intensity coding in the auditory nerve, we did not find strong evidence for hypothesized coding-in-noise deficits; (3) the sensitivity and the usefulness of the envelope following responses to amplitude modulation signals in detecting cochlear synaptopathy is questionable.
Topics: Animals; Auditory Perception; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Noise-Induced; Humans; Otoacoustic Emissions, Spontaneous; Synapses
PubMed: 30267832
DOI: 10.1016/j.neuroscience.2018.09.026 -
The Journal of International Advanced... Mar 2022To investigate the possible protective activity of oleuropein compound on noise-induced hearing loss in rats.
BACKGROUND
To investigate the possible protective activity of oleuropein compound on noise-induced hearing loss in rats.
METHODS
Twenty-eight adult male albino rats were divided into 4 groups. Control normal saline (n=7) group was kept noise-free. Control oleuropein group (n=7) group was kept noise-free and was administered with 50 mg/kg/day oleuropein. The experimental normal saline (n=7) group was subjected to noise. The experimental oleuropein (n=7) group was subjected to noise and was administered with 50 mg/kg/day oleuropein. The experimental groups were subjected to 4 kHz octave noise with a frequency of 120 dB Sound Pressure Level (SPL) for 4 hours. Hearing level measurements were performed with auditory brainstem response and distortion-product otoacoustic emission tests before and after the 1st, 7th, and 10th day of the noise exposure. On the 10th day, rats were sacrificed. The temporal bones of the rats were removed and the cochlea and spiral ganglion cells were evaluated using hematoxylin-eosin staining under light microscopy.
RESULTS
Better hearing thresholds were achieved in the experimental oleuropein group compared to the experimental normal saline group at 8 kHz, 12 kHz, 16 kHz, and 32 kHz frequencies (P < .05). Although no statistically significant difference was found between the groups, in the experimental normal saline group, the percentage of damaged spiral ganglion cells was higher than the experimental oleuropein group.
CONCLUSION
Our findings suggest that oleuropein may have a partial protective effect against noise-related hearing loss. However, further research with higher doses is needed to justify this protective effect.
Topics: Animals; Auditory Threshold; Cochlea; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Noise-Induced; Iridoid Glucosides; Male; Otoacoustic Emissions, Spontaneous; Rats; Saline Solution
PubMed: 35418359
DOI: 10.5152/iao.2022.20009 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jul 2020The symptoms of hidden hearing loss(HHL) are concealed, mainly manifested as defects in the threshold upper auditory function, which are related to noise exposure,... (Review)
Review
The symptoms of hidden hearing loss(HHL) are concealed, mainly manifested as defects in the threshold upper auditory function, which are related to noise exposure, aging and drug damage. There is no definite evidence to prove that whether the three factors participate in mechanism of synaptic damage in the cochlea. The clinical audiological characteristics of HHL are mostly as follows: the normal threshold of PTA and the wave response of ABR; the amplitude of the CAP of ABR wave Ⅰ or ECochG is lower at medium and high stimulation intensity; the lower speech recognition rate under noise, etc. Ultra-high frequency pure tone audiometry, a series of objective audiological examinations, such as ABR, ECochG and frequency-following response, speech audiometry under noise, noise exposure questionnaire evaluation were applied to detect HHL at early stage.
Topics: Acoustic Stimulation; Audiometry, Pure-Tone; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Noise-Induced; Humans; Noise
PubMed: 32791650
DOI: 10.13201/j.issn.2096-7993.2020.07.023 -
Temporary and Permanent Noise-induced Threshold Shifts: A Review of Basic and Clinical Observations.Otology & Neurotology : Official... Sep 2016To review basic and clinical findings relevant to defining temporary (TTS) and permanent (PTS) threshold shifts and their sequelae. (Review)
Review
OBJECTIVE
To review basic and clinical findings relevant to defining temporary (TTS) and permanent (PTS) threshold shifts and their sequelae.
DATA SOURCES
Relevant scientific literature and government definitions were broadly reviewed.
DATA SYNTHESIS
The definitions and characteristics of TTS and PTS were assessed and recent advances that expand our knowledge of the extent, nature, and consequences of noise-induced hearing loss were reviewed.
CONCLUSION
Exposure to intense sound can produce TTS, acute changes in hearing sensitivity that recover over time, or PTS, a loss that does not recover to preexposure levels. In general, a threshold shift ≥10 dB at 2, 3, and 4 kHz is required for reporting purposes in human studies. The high-frequency regions of the cochlea are most sensitive to noise damage. Resonance of the ear canal also results in a frequency region of high-noise sensitivity at 4 to 6 kHz. A primary noise target is the cochlear hair cell. Although the mechanisms that underlie such hair cell damage remain unclear, there is evidence to support a role for reactive oxygen species, stress pathway signaling, and apoptosis. Another target is the synapse between the hair cell and the primary afferent neurons. Large numbers of these synapses and their neurons can be lost after noise, even though hearing thresholds may return to normal. This affects auditory processing and detection of signals in noise. The consequences of TTS and PTS include significant deficits in communication that can impact performance of military duties or obtaining/retaining civilian employment. Tinnitus and exacerbation of posttraumatic stress disorder are also potential sequelae.
Topics: Animals; Auditory Threshold; Hearing Loss, Noise-Induced; Humans; Noise
PubMed: 27518135
DOI: 10.1097/MAO.0000000000001071