Mechanism underlying adaptation at the inner hair cell ribbon synapse

JUAN D. GOUTMAN; ELISABETH GLOWATZKI

Denver, CO, USA

Congreso; XXX ARO MidWinter Meeting; 2007

Association for Research in Otolaryngology

Auditory nerve activity shows adaptation in response to prolonged sound stimulation. It has been proposed, that the site of adaptation is the inner hair cell (IHC) afferent synapse, as the IHC receptor potential and the IHC calcium currents do not adapt in a way as the auditory nerve response does. We studied the role the IHC afferent synapse plays in auditory nerve adaptation by performing simultaneous whole cell recordings from IHCs and corresponding afferent fiber dendrites (AFs) in the postnatal rat organ of Corti (P9-P11). To activate maximal calcium current and transmitter release, IHCs were depolarized with voltage steps from -89 to -29 mV for 1s every 30 s.   IHC calcium currents were isolated pharmacologically and excitatory postsynaptic currents (EPSCs) in the AF response were monitored at a holding potential of -84 mV.  The AF responses to IHC depolarization very much resembled auditory nerve fiber responses to sound: The activity dropped to about 10% of the initial response within a second. The decay in activity was fit with two exponentials, the time constants were around 10 ms and 100 ms. The role of AMPA receptors desensitization was tested by recording in 100 microM cyclothiazide, to remove receptor desensitization. The AF response still adapted but with a slower time course. This remaining adaptation is most likely due to exhaustion of the presynaptic pools of vesicles. The rate of vesicle release (obtained by deconvolution of the AF response with an average EPSC) showed a sharp initial peak (3 ms duration) and a second component that relaxed into a steady state. The recordings were repeated with different strength of calcium buffering of the IHC, to investigate the role of different vesicle pools in the time course of release. In summary, both desensitization of AMPA receptors and exhaustion of vesicle release contribute to adaptation at the IHC afferent synapse.