Cochlear protection against noise exposure requires serotonin type 3A receptor via the medial olivocochlear system

The cochlear efferent feedback system plays important roles in auditory processing, including regulation of the dynamic range of hearing, and provides protection against acoustic trauma. These functions are performed through medial olivocochlear (MOC) neurons. However, the underlying cellular and molecular mechanisms are not fully understood. The serotonin type 3A (5-HT3A) receptor is widely expressed throughout the nervous system, which suggests important roles in various neural functions. However, involvement of the 5-HT3A receptor in the MOC system remains unclear. We used mice in this study and found that the 5-HT3A receptor was expressed in MOC neurons that innervated outer hair cells in the cochlea and was involved in the activation of MOC neurons by noise exposure. 5-HT3A receptor knockout impaired MOC functions, potentiated noise-induced hearing loss, and increased loss of ribbon synapses following noise exposure. Furthermore, 5-HT3 receptor agonist treatment alleviated the noise-induced hearing loss and loss of ribbon synapses, which enhanced cochlear protection provided by the MOC system. Our findings demonstrate that the 5-HT3A receptor plays fundamental roles in the MOC system and critically contributes to protection from noise-induced hearing impairment.