Time course and calcium dependence of transmitter release at a single ribbon synapse

Abstract

At the first synapse in the auditory pathway, the receptor potential of mechanosensory hair cells is converted into a firing pattern in auditory nerve fibers. For the accurate coding of timing and intensity of sound signals, transmitter release at this synapse must occur with the highest precision. To measure directly the transfer characteristics of the hair cell afferent synapse, we implemented simultaneous whole-cell recordings from mammalian inner hair cells (IHCs) and auditory nerve fiber terminals that typically receive input from a single ribbon synapse. During a 1-s IHC depolarization, the synaptic response depressed >90%, representing the main source for adaptation in the auditory nerve. Synaptic depression was slightly affected by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization; however, it was mostly caused by reduced vesicular release. When the transfer function between transmitter release and Ca²⁺ influx was tested at constant open probability for Ca²⁺ channels (potentials >0 mV), a super linear relation was found. This relation is presumed to result from the cooperative binding of three to four Ca²⁺ ions at the Ca²⁺ sensor. However, in the physiological range for receptor potentials (−50 to −30 mV), the relation between Ca²⁺ influx and afferent activity was linear, assuring minimal distortion in the coding of sound intensity. Changes in Ca²⁺ influx caused an increase in release probability, but not in the average size of multivesicular synaptic events. By varying Ca²⁺ buffering in the IHC, we further investigate how Ca²⁺ channel and Ca²⁺ sensor at this synapse might relate.