Role of the a10 nicotinic cholinergic receptor in the development and function of the olivocochlear system

VETTER, D.E; KATZ, E.; MAISON, S.F; TARANDA, J; HUANG, C; LIBERMAN, M.C.,; ELGOYHEN, A.B; BOULTER, J

New Orleans, USA

Congreso; 28th Midwinter Meeting, Association for Research in Otolaryngology; 2005

The hair cell nAChR mediating neurotransmission at the olivocochlear (OC) synapse is postulated to be encoded by the a9 and a10 nAChR subunit genes. While a9 functions as a homomeric receptor in heterologous expression assays, generation of the native hair cell-like physiology requires a10 co-expression. Changes in the expression level of a10 mRNA during normal postnatal development correlate with sensitivity of IHCs to ACh. However, the precise function played by the a10 gene in auditory processing is unknown. We have therefore generated a10 gene null mutant mice to assess the role of the a10 gene in auditory processing. nAChR a10 mutant mice were genetically engineered using standard gene targeting techniques. Homozygous a10 mutant mice breed normally and show no overt behavioral phenotype. Immunostaining using antibodies staining nerve terminals to examine the nature of the OC innervation, revealed hypertrophied OC synaptic terminals on OHCs of the a10 null mice similar to those we described for the a9 knockouts. No changes in threshold (relative to wildtype littermates) were observed in the a10 null mice as assessed by ABR across a frequency spectrum spanning 8-32 kHz. DPOAE amplitudes during OC stimulation, however, were enhanced compared to the normal suppression observed in wildtype controls. Whole cell electrophysiological recordings of IHCs obtained from acutely excised P8-9 organs of Corti revealed no ACh-inducible responses or K-induced synaptic activity in IHCs of a10 knockouts. In preliminary experiments, however, ACh evoked responses in 1 out of 3 OHCs (P11-12). Wildtype and heterozygous littermates showed robust ACh-evoked responses and K-induced synaptic activity in all IHCs and OHCs tested at the same ages. These results suggest that the lack of the a10 subunit gene has a different impact on auditory physiology than that observed in the a9 null mice.