ATP modulates synaptic activity at the efferent-inner hair cell synapse in the developing inner ear

ALVAREZ HEDUAN F; KATZ E; GOUTMAN J; ELGOYHEN AB

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2012

Before the onset of hearing (P14) mammalian inner hair cells (IHCs) are transiently innervated by medial olivocochlear (MOC) efferent fibers. Acetylcholine (ACh) released by these fibers binds post-synaptic calcium-permeable a9a10 nicotinic receptors which, in turn, activate SK2 calcium-activated potassium channels, leading to inhibitory post synaptic currents (IPSCs) at the IHCs. During this period IHCs fire spontaneous sensory-independent action potentials, driven by ATP released from cochlear supporting cells. This activity is essential for neuronal survival and for the refinement of tonotopic maps upstream in the auditory pathway. MOC fibers play a roll in controlling this activity. In this context, ATP could also fine tune efferent synaptic transmission during this period. Therefore, we investigated the effect of ATP on the release of ACh at the mouse MOC-IHC synapse. IPSCs, evoked by electrically stimulating MOC fibers, were recorded in voltage-clamped (-90 mV) IHCs from acutely isolated organs of Corti at P9-P12. We found that 100 mM ATP reversibly decreased the quantal content of evoked release (46.9±9.4%, n=6, p<0.05) and the frequency of spontaneous IPSCs (43.1±13.3%, n=6, p<0.05). In addition, spontaneous IPSCs amplitude was also reduced (22.3±8.1 %, n=6, p<0.05). These results suggest that ATP has both pre and post synaptic effects, exerting a putative role in modulating the inhibitory activity of MOC fibers during development. We are currently studying which ATP receptors are responsible for this modulation.