Changes in the kinetic properties of the a9a10 hair cell nicotinic receptor increase the level of olivocochlear inhibition in auditory synapses

Abstract

Medial olivocochlear (MOC) fibers innervate the cochlear outer (OHCs) hair cells and also transiently during development, the inner hair cells (IHCs). The MOC-hair cell synapse is cholinergic, inhibitory and is mediated by a9a10 nicotinic receptors (nAChR). In mice bearing a point mutation in the a9 nAChR subunit (Kin), in-vivo cochlear efferent-mediated inhibition is dramatically lengthened and enhanced (Taranda 2009). We now investigated whether there are changes in the short-term plasticity properties (STP) of MOC-hair cells synapses that could account for this enhanced efferent suppression. Evoked synaptic currents were recorded in IHCs and OHCs of isolated mouse organs of Corti. MOC-OHC synapses from Kin mice significantly facilitated upon 20 and 40 Hz stimulation (p2/p1- 20Hz= 2.6; p2/p1- 40Hz= 3.2; n=4-8). The probability of release increased during the trains, whereas the size of the events remained stable suggesting a presynaptic origin. Moreover, stimulation of MOC fibers at 80 Hz for 10 s resulted in postsynaptic responses of longer duration and slower onset times in both OHCs and IHCs from Kin mice (n=8-16). In accordance, preliminary experiments show that efferent inhibition of calcium action potentials is more potent in IHCs from kin mice. We conclude that the alteration in the STP patterns of MOC-hair cell synapses caused by the mutation could contribute to the observed changes in the dynamics of in-vivo cochlear efferent inhibition.