RT Journal Article SR Electronic T1 Transmitter Release from Cochlear Hair Cells Is Phase Locked to Cyclic Stimuli of Different Intensities and Frequencies JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 17025 OP 17036 DO 10.1523/JNEUROSCI.0457-12.2012 VO 32 IS 47 A1 Juan D. Goutman YR 2012 UL http://www.jneurosci.org/content/32/47/17025.abstract AB The auditory system processes time and intensity through separate brainstem pathways to derive spatial location as well as other salient features of sound. The independent coding of time and intensity begins in the cochlea, where afferent neurons can fire action potentials at constant phase throughout a wide range of stimulus intensities. We have investigated time and intensity coding by simultaneous presynaptic and postsynaptic recording at the hair cell-afferent synapse from rats. Trains of depolarizing steps to the hair cell were used to elicit postsynaptic currents that occurred at constant phase for a range of membrane potentials over which release probability varied significantly. To probe the underlying mechanisms, release was examined using single steps to various command voltages. As expected for vesicular release, first synaptic events occurred earlier as presynaptic calcium influx grew larger. However, synaptic depression produced smaller responses with longer first latencies. Thus, during repetitive hair cell stimulation, as the hair cell is more strongly depolarized, increased calcium channel gating hurries transmitter release, but the resulting vesicular depletion produces a compensatory slowing. Quantitative simulation of ribbon function shows that these two factors varied reciprocally with hair cell depolarization (stimulus intensity) to produce constant synaptic phase. Finally, we propose that the observed rapid vesicle replenishment would help maintain the vesicle pool, which in turn would equilibrate with the stimulus intensity (and therefore the number of open Ca2+ channels), so that for trains of different levels the average phase will be conserved.