TY - JOUR T1 - Efferent control of hearing sensitivity and protection via inner ear supporting cells JF - bioRxiv DO - 10.1101/2020.12.03.409946 SP - 2020.12.03.409946 AU - Hong-Bo Zhao AU - Li-Man Liu AU - Ling Mei AU - Ning Yu AU - Jin Chen AU - Yan Zhu AU - Chun Liang Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/04/2020.12.03.409946.abstract N2 - It is critical for hearing that the descending cochlear efferent system provide negative feedback to hair cells to regulate hearing sensitivity and provide protection from noise. The medial olivocochlear (MOC) efferent nerves project to outer hair cells (OHCs) and inhibit OHC electromotility, which is an active cochlear amplification and can increase hearing sensitivity. Here, we report that the MOC efferent nerves also have functional innervation with the cochlear supporting cells to regulate hearing sensitivity. The MOC efferent nerve fibers and the corresponding MOC neurotransmitter acetylcholine (ACh) receptors were visible in the cochlear supporting cells. Application of ACh in the cochlear supporting cells could also evoke inward currents in a dose-dependent manner and reduced gap junctional (GJ) coupling between the cochlear supporting cells, which consequently declined electromotility in OHCs. This indirect inhibitory effect through the mediated GJs between the cochlear supporting cells on OHC electromotility was consistent and enhanced the direct inhibition of ACh on OHC electromotility but had long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent control pathway declined the regulation of active cochlear amplification and impaired the protection from noise trauma. Our findings reveal a new pathway for the cochlear efferent system to control hearing sensitivity, and also demonstrate that this supporting cell GJ-mediated efferent pathway is critical for control of hearing sensitivity and the protection of hearing from noise trauma.Significance statement The cochlear efferent system provides a negative feedback loop to hair cells and plays a critical role in the regulation of hearing sensitivity and protection from noise trauma. In this study, we found that besides projection to outer hair cells (OHCs), the medial olivocochlear (MOC) efferent system has innervation with cochlear supporting cells and regulate gap junctions (GJs) between supporting cells to control OHC electromotility and hearing sensitivity. Deficiency of this supporting cell GJ-mediated efferent pathway could impair the regulation of active cochlear amplification and increased susceptibility to noise. Our findings demonstrate that the MOC efferent system not only directly inhibits OHC activity but also can control GJs between supporting cells to regulate hearing sensitivity, which plays a critical role in the protection from noise trauma.Competing Interest StatementThe authors have declared no competing interest. ER -