Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells.

It is critical for hearing that the descending cochlear efferent system provides a negative feedback to hair cells to regulate hearing sensitivity and protect hearing from noise. The medial olivocochlear (MOC) efferent nerves project to outer hair cells (OHCs) to regulate OHC electromotility, which is an active cochlear amplifier and can increase hearing sensitivity. Here, we report that the MOC efferent nerves also could innervate supporting cells (SCs) in the vicinity of OHCs to regulate hearing sensitivity. MOC nerve fibers are cholinergic, and acetylcholine (ACh) is a primary neurotransmitter. Immunofluorescent staining showed that MOC nerve endings, presynaptic vesicular acetylcholine transporters (VAChTs), and postsynaptic ACh receptors were visible at SCs and in the SC area. Application of ACh in SCs could evoke a typical inward current and reduce gap junctions (GJs) between them, which consequently enhanced the direct effect of ACh on OHCs to shift but not eliminate OHC electromotility. This indirect, GJ-mediated inhibition had a long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent pathway decreased the regulation of active cochlear amplification and compromised the protection against noise. In particular, distortion product otoacoustic emission (DPOAE) showed a delayed reduction after noise exposure. Our findings reveal a new pathway for the MOC efferent system via innervating SCs to control active cochlear amplification and hearing sensitivity. These data also suggest that this SC GJ-mediated efferent pathway may play a critical role in long-term efferent inhibition and is required for protection of hearing from noise trauma. The cochlear efferent system provides a negative feedback to control hair cell activity and hearing sensitivity and plays a critical role in noise protection. We reveal a new efferent control pathway in which medial olivocochlear efferent fibers have innervations with cochlear supporting cells to control their gap junctions, therefore regulating outer hair cell electromotility and hearing sensitivity. This supporting cell gap junction-mediated efferent control pathway is required for the protection of hearing from noise.