Mechanisms of transmitter release at the inner hair cell ribbon synapse

JUAN D. GOUTMAN

Simposio; Simposio ?International Hearing Research & Closing the auditory efferent loop III?; 2018

Inner hair cells (IHC) in the cochlea are the mammalian phono-receptors, transducing sound energy into graded changes in membrane potentials, the so called ?receptor potentials?. Ribbon synapses between IHC and auditory nerve neurons are responsible for converting receptor potentials into spike rates. The characteristics of auditory nerve responses to acoustic stimuli have been described extensively, and in recent years multiple features of the ribbon synapse function have been shown to contribute to sound encoding. For instance, persistent acoustic stimulation produces sensory adaptation, that is revealed as a reduction in neuronal spike rate with time constants in the range of milliseconds to seconds. In this work, we focused on the mechanisms operating at the IHC ribbon synapse that allow the auditory nerve to adapt to constant stimuli. Since the amplitude of IHC receptor potentials is invariant during the period of fast adaptation, classical hypothesis pointed to vesicle depletion at the IHC as responsible for auditory adaptation. In this study, we observed that fast synaptic depression occurred in responses to stimuli of varying intensities. Nevertheless, release continued after this initial depression, via synaptic vesicles with slower exocytotic kinetics. Heterogeneity in kinetic elements, therefore, favored synaptic responses with an early peak and a sustained phase. The application of cyclothiazide (CTZ) revealed that desensitization of postsynaptic receptors contributed to synaptic depression, which was more pronounced during stronger stimulation. Thus, desensitization had a two-fold effect: it abbreviated signaling between IHC and the auditory nerve, and also, balanced differences in decay kinetics between responses to different stimulation strengths. We therefore propose that both pre and postsynaptic mechanisms at the IHC ribbon synapse contribute to synaptic depression at the IHC ribbon synapse, and spike rate adaptation in the auditory nerve.