Olivocochlear function in nAChR a10 ‘knockout’ mice.

DOUGLAS E. VETTER; ELEONORA KATZ; STEPHANE F. MAISON; JULIAN TARANDA; CHENGHANG HUANG; M. CHARLES LIBERMAN; A. BELEN ELGOYHEN; JIM BOULTER

Washington, USA

Congreso; 35th Society for Neuroscience Annual Meeting; 2005

The hair cell nAChR at the olivocochlear (OC) synapse is 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 level of a10 mRNA during normal postnatal development correlate with increased sensitivity of IHCs to ACh; however, the precise function played by the a10 gene in auditory processing is unknown. We have therefore generated a10 -  ‘knockout’ mice to assess the role of the a10 gene in the development and function of the OC system. Homozygous a10 mutant mice breed normally and show no overt behavioral phenotype. Antibody staining of nerve terminals revealed hypertrophied OC synaptic terminals on OHCs in a10 null mice reminiscent of those described for the a9 knockouts. Relative to wild type littermates, no changes in threshold were observed in the a10 null mice as assessed by ABR (Auditory Brainstem Response) across a frequency spectrum spanning 8-32 kHz. DPOAE (Distortion Products Otoacustic Emissions) amplitudes during OC stimulation, however, were enhanced compared to the 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.