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Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9719-9724. doi: 10.1073/pnas.1706160114. Epub 2017 Aug 21.

Mechanisms of synaptic depression at the hair cell ribbon synapse that support auditory nerve function.

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Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Héctor N. Torres" (INGEBI) (Consejo Nacional de Investigaciones Científicas y Técnicas), C1428ADN C. A. Buenos Aires, Argentina


Inner hair cells (IHCs) 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 IHCs and auditory nerve neurons are responsible for converting receptor potentials into spike rates. The characteristics of auditory nerve responses to sound have been described extensively. For instance, persistent acoustic stimulation produces sensory adaptation, which is revealed as a reduction in neuronal spike rate with time constants in the range of milliseconds to seconds. Since the amplitude of IHC receptor potentials is invariant during this period, the classic 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 twofold 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.


adaptation; desensitization; hair cell; synaptic depression

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