Role of alpha 9 Nicotinic ACh Receptor Subunits in the Development and Function of Cochlear Efferent Innervation

Cochlear outer hair cells (OHCs) express alpha 9 nACh receptors and are contacted by descending, predominately cholinergic, efferent fibers originating in the CNS. Mice carrying a null mutation for the nACh alpha 9 gene were produced to investigate its role(s) in auditory processing and development of hair cell innervation. In alpha 9 knockout mice, most OHCs were innervated by one large terminal instead of multiple smaller terminals as in wild types, suggesting a role for the nACh alpha 9 subunit in development of mature synaptic connections. alpha 9 knockout mice also failed to show suppression of cochlear responses (compound action potentials, distortion product otoacoustic emissions) during efferent fiber activation, demonstrating the key role alpha 9 receptors play in mediating the only known effects of the olivocochlear system.