Efferent Inhibition of Hair Cells: Past, Present and Future

Efferent modulation of vertebrate auditory organs has been known since the early twentieth century, mediated by cholinergic brainstem neurons. In mammals, medial olivocochlear neurons release acetylcholine (ACh) to inhibit outer hair cells to reduce cochlear sensitivity and tuning through an unusual mechanism of nicotinic inhibition, employing unique α9α10-containing AChRs (nAChRs). This synaptic mechanism and orthologous nAChRs, are conserved among vertebrate hair cells. Genetic modification of α9α10-containing nAChRs has cemented the role of efferent feedback in protection against noise-induced hearing loss in mice. Virally-mediated introduction of gain-of-function nAChRs reduces the impact of acoustic trauma in wildtype mice, encouraging development of cholinergic gene therapy for clinical application.