{"title":"Efferent Inhibition of Hair Cells: Past, Present and Future.","authors":"Paul Albert Fuchs","doi":"10.1007/s10162-026-01045-z","DOIUrl":null,"url":null,"abstract":"<p><p>Efferent modulation of vertebrate auditory organs has been known since the early twentieth century, mediated by cholinergic brainstem neurons. In mammals, medial olivocochlear neurons release acetylcholine (ACh) to inhibit outer hair cells to reduce cochlear sensitivity and tuning through an unusual mechanism of nicotinic inhibition, employing unique α9α10-containing AChRs (nAChRs). This synaptic mechanism and orthologous nAChRs, are conserved among vertebrate hair cells. Genetic modification of α9α10-containing nAChRs has cemented the role of efferent feedback in protection against noise-induced hearing loss in mice. Virally-mediated introduction of gain-of-function nAChRs reduces the impact of acoustic trauma in wildtype mice, encouraging development of cholinergic gene therapy for clinical application.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"331-342"},"PeriodicalIF":2.9000,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237425/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jaro-Journal of the Association for Research in Otolaryngology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10162-026-01045-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/4/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Efferent modulation of vertebrate auditory organs has been known since the early twentieth century, mediated by cholinergic brainstem neurons. In mammals, medial olivocochlear neurons release acetylcholine (ACh) to inhibit outer hair cells to reduce cochlear sensitivity and tuning through an unusual mechanism of nicotinic inhibition, employing unique α9α10-containing AChRs (nAChRs). This synaptic mechanism and orthologous nAChRs, are conserved among vertebrate hair cells. Genetic modification of α9α10-containing nAChRs has cemented the role of efferent feedback in protection against noise-induced hearing loss in mice. Virally-mediated introduction of gain-of-function nAChRs reduces the impact of acoustic trauma in wildtype mice, encouraging development of cholinergic gene therapy for clinical application.
期刊介绍：
JARO is a peer-reviewed journal that publishes research findings from disciplines related to otolaryngology and communications sciences, including hearing, balance, speech and voice. JARO welcomes submissions describing experimental research that investigates the mechanisms underlying problems of basic and/or clinical significance.
Authors are encouraged to familiarize themselves with the kinds of papers carried by JARO by looking at past issues. Clinical case studies and pharmaceutical screens are not likely to be considered unless they reveal underlying mechanisms. Methods papers are not encouraged unless they include significant new findings as well. Reviews will be published at the discretion of the editorial board; consult the editor-in-chief before submitting.
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