The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

Although homomeric channels assembled from the alpha 9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via hetero-meric nAChRs composed of both a9 and alpha 10 subunits. To gain insight into alpha 10 subunit function in vivo, we examined olivocochlear innervation and function in alpha 10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in alpha 10(+/+) and alpha 10(+/-) mice, with no detectable responses to ACh in alpha 10(-/-) mice. In contrast, a proportion of alpha 10(-/-) outer hair cells showed small ACh-evoked currents. In alpha 10(-/-) mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual a9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, alpha 10(-/-) mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. our results demonstrate that alpha 9(-/-) and alpha 10(-/-) mice have overlapping but nonidentical phenotypes. Moreover, alpha 10 nAChR subunits are required for normal olivocochlear activity because a9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in alpha 10(-/-)mutant mice.