Phenotypic changes of auditory nerve fibers after excitotoxicity

• 成果类型: Article
• 署名作者: Diuba, Artem; Gratias, Paul; Jeffers, Penelope W. C.; Nouvian, Regis; Puel, Jean- Luc; Kujawa, Sharon G.; Bourien, Jerome
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Harvard University; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Harvard University; Universite de Montpellier; Harvard University; Harvard Medical School
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11880
• DOI: 10.1073/pnas.2412332122
• 发表日期: 2024-04-08
• 关键词: hair cell loss; kainic acid; cochlear synaptopathy; ribbon synapses; hearing-loss; otoacoustic emissions; afferent synapses; induced damage; degeneration; expression

摘要

There is a substantial body of evidence elucidating the pathophysiological aspects of excitotoxicity in the mammalian cochlea. However, the question of whether the resultant damage is reversible remains unresolved. To replicate an excitotoxic event, we investigated the long- term effects of kainate application in gerbil cochleae. Surprisingly, despite persistent synapse loss, the compound action potential of the auditory nerve fully recovered. This functional retrieval was associated with a phenotypic change in auditory nerve fibers. Thresholds were improved along the tonotopic axis. High- spontaneous rate (SR) fibers largely populated the apical region, while low- SR fibers from the basal region exhibited sound- driven activity indistinguishable from control high- SR fibers. This functional phenotype change may support the full recovery of neural response thresholds and amplitudes after excitotoxicity. Furthermore, hyperresponsiveness of the auditory nerve fibers could be a crucial factor in the development of hyperactivity in the central auditory pathways, a common occurrence following acoustic overstimulation.