{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:47:41Z","timestamp":1782280061780,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,4]]},"group-title":"Neuroscience","reference-count":104,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH Grant","award":["R01 DC001508"],"award-info":[{"award-number":["R01 DC001508"]}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y T\u00e9cnica","doi-asserted-by":"crossref","award":["pict-2021-00818"],"award-info":[{"award-number":["pict-2021-00818"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The early onset of peripheral deafness significantly alters the proper development of the auditory system. Likewise, exposure to loud noise during early development produces a similar disruptive effect. Before hearing onset in altricial mammals, cochlear inner hair cells exhibit spontaneous electrical activity that drives auditory circuit development. This activity is modulated by medial olivocochlear (MOC) efferent feedback through \u03b19\u03b110 nicotinic cholinergic receptors in inner hair cells. In adults, these receptors are restricted to outer hair cells, where they mediate MOC feedback to regulate cochlear amplification. Although the MOC system\u2019s protective role to prevent noise-induced hearing loss in adulthood is well-established, its influence during early developmental stages-especially in response to exposure to loud noise-remains largely unexplored. In this study, we investigated the role of MOC feedback during early postnatal development using \u03b19 knockout (KO) and \u03b19 knock-in (KI) mice of either sex, which respectively lack or exhibit enhanced cholinergic activity. Our findings reveal that both increased and absent olivocochlear activity result in altered auditory sensitivity at the onset of hearing, along with long\u2013 range alterations in the number and morphology of ribbon synapses. Early noise exposure caused lasting auditory damage in both wild-type and \u03b19KO mice, with deficits persisting into adulthood. In contrast, \u03b19KI mice were protected from noise-induced damage, with no long-term effects on auditory function. These results highlight the increased susceptibility of the auditory system during early postnatal development. Moreover, they indicate that an enhanced MOC feedback shields the auditory system from noise damage during this period.<\/jats:p>\n                <jats:sec>\n                  <jats:title>SIGNIFICANCE STATEMENT<\/jats:title>\n                  <jats:p>Early development represents a sensitive window for shaping auditory function. We show that the medial olivocochlear system is critical for establishing normal ribbon synapse density and size; key features for proper hearing onset. We also show that the developing auditory system is especially vulnerable to loud noise, with early exposure causing more severe and lasting effects than similar noise later in life. Notably, enhancing \u03b19\u03b110 nAChR receptor activity during this early stage offers protection against noise-induced damage, revealing a time-sensitive opportunity to safeguard auditory development.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.03.631257","type":"posted-content","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T18:15:11Z","timestamp":1736273711000},"source":"Crossref","is-referenced-by-count":1,"title":["Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1453-3372","authenticated-orcid":false,"given":"Valeria C.","family":"Castagna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-616X","authenticated-orcid":false,"given":"Luis E.","family":"Boero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3918-296X","authenticated-orcid":false,"given":"Mariano N.","family":"Di Guilmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Catalano","family":"Di Meo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena A.","family":"Ballestero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4627-4114","authenticated-orcid":false,"given":"Paul A.","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-7374","authenticated-orcid":false,"given":"Amanda M.","family":"Lauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-0311","authenticated-orcid":false,"given":"Ana Bel\u00e9n","family":"Elgoyhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-8274","authenticated-orcid":false,"given":"Maria Eugenia","family":"Gomez-Casati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025070807150416000_2025.01.03.631257v3.1","unstructured":"Antoli-Candela FJ , Kiang N (1978) Unit activity underlying the N1 potential. 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