Cochlear outer hair cells (OHCs) express α9 nACh receptors and are contacted by descending, predominately cholinergic, efferent fibers originating in the CNS. Mice carrying a null mutation for the nACh α9 gene were produced to investigate its role(s) in auditory processing and development of hair cell innervation. In α9 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 α9 subunit in development of mature synaptic connections. α9 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 α9 receptors play in mediating the only known effects of the olivocochlear system.
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