Phenotypic changes of auditory nerve fibers after excitotoxicity

IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-04-01 DOI:10.1073/pnas.2412332122
Artem Diuba, Paul Gratias, Penelope W. C. Jeffers, Régis Nouvian, Jean-Luc Puel, Sharon G. Kujawa, Jérôme Bourien
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Abstract

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.
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兴奋性中毒后听觉神经纤维的表型变化
有大量的证据阐明了哺乳动物耳蜗兴奋性毒性的病理生理方面。然而,由此产生的损害是否可逆的问题仍然没有解决。为了重复兴奋毒性事件,我们研究了盐酸盐在沙鼠耳蜗中的长期作用。令人惊讶的是,尽管持续的突触丢失,听觉神经的复合动作电位完全恢复。这种功能恢复与听觉神经纤维的表型改变有关。阈值沿异位轴提高。高自发率(SR)纤维主要分布在根尖区域,而来自基底区的低自发率纤维表现出与对照高自发率纤维没有区别的声音驱动活动。这种功能性表型改变可能支持兴奋毒性后神经反应阈值和振幅的完全恢复。此外,听觉神经纤维的高反应性可能是中枢听觉通路过度活跃发展的关键因素,这是听觉过度刺激后常见的现象。
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来源期刊
CiteScore
19.00
自引率
0.90%
发文量
3575
审稿时长
2.5 months
期刊介绍: The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
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