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Deciphering the underlying pathophysiological mechanisms remains challenging owing to the diversity of spiral ganglion neuron subtypes and associated central auditory circuits. An auditory neuropathy mechanism is unraveled by investigating the origin of auditory hyperexcitability in a mouse model for hereditary congenital deafness. <jats:italic>Otogl<\/jats:italic> encodes the large Otogelin\u2010like protein, which is related to secreted epithelial mucins and is implicated in the mechanical stimulation of cochlear outer hair cells. Heterozygous <jats:italic>Otogl<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mutant mice display auditory hyperexcitability, highlighted by their susceptibility to audiogenic seizures induced by loud sounds. It is shown that <jats:italic>Otogl<\/jats:italic> is transiently expressed in a subpopulation of spiral ganglion neurons during cochlear development. Despite their apparently normal hearing, <jats:italic>Otogl<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice display poor activation of the spiral ganglion neurons processing loud sounds and an elevation of the activation threshold of the middle the ear muscle reflex that attenuates loud sounds. The findings reveal how a neuropathy affecting spiral ganglion neurons specialized in loud sound processing and associated with the middle the ear muscle reflex can manifest itself as auditory hyperexcitability.<\/jats:p>","DOI":"10.1002\/advs.202410776","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T14:19:51Z","timestamp":1739888391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Deciphering Auditory Hyperexcitability in <i>Otogl<\/i> Mutant Mice Unravels an Auditory Neuropathy Mechanism"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0399-4667","authenticated-orcid":false,"given":"Mathilde","family":"Gagliardini","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut Pasteur, AP\u2010HP, INSERM, CNRS, Fondation Pour l'Audition, Institut de l'Audition, IHU reConnect Plasticity of Central Auditory 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