Transmitter release from cochlear hair cells is phase-locked to cyclic stimuli of different intensities and frequencies.

JUAN D. GOUTMAN

Congreso; 36th Annual MidWinter Meeting of the Association for Research in Otolaryngology; 2013

Transmitter Release from Cochlear Hair Cells is Phase-Locked to Cyclic Stimuli of Different Intensities and Frequencies. Background. The auditory system analyzes time and intensity to code location of a sound source. These parameters are preferentially processed in different brainstem nuclei and so must be independently detected in the periphery and transmitted to the central nervous system. It is well-established that auditory nerve fibers are able to fire at a particular time within each cycle of a low-frequency periodic stimulus. Furthermore, this preferred phase can remain constant over a range of sound intensities at the characteristic frequency – phase constancy independent of intensity. We investigated this phenomenon at the first synapse of the hearing pathway, between inner hair cells and boutons of auditory nerve neurons. Methods. Explants of the organ of Corti from neonatal rats were used for experiments (apical region). Simultaneous pre- and post-synaptic patch-clamp recordings at the inner hair cell-afferent synapse were performed. The series of differential equations corresponding to a model of the inner hair cell calcium sensor were solved numerically. Results. Cyclic stimuli such as trains of depolarizations to different potentials were presynaptically applied, trying to mimic acoustic stimuli of different intensities. Synaptic responses elicited by these trains presented constant latencies (or phase) within each cycle, for a range of membrane potentials over which release probability varied significantly. Phase-locked release was observed with stimulating frequencies of 100, 250 and 500 Hz. In contrast, on single steps, synaptic responses proved to have a voltage-(calcium-) dependence on timing. Interestingly, short-term facilitation (only) partially compensated for changes in latencies (and also reduced jitter) in these single pulses. We also found that synaptic depression elicited longer 1st latencies events. Thus, during repetitive presynaptic stimulation, as hair cells are more strongly depolarized, increased calcium channel gating would speed up transmitter release, but the resulting vesicular depletion produced a compensatory slowing. Quantitative simulation of ribbon function showed that these two factors will vary reciprocally with hair cell depolarization (stimulus intensity) to produce constant synaptic phase. Conclusions. We propose that equilibrium would be established between each stimuli level and the degree of synaptic depression. Stronger stimuli accelerate release kinetics but operate on a smaller vesicular pool, which in contrast, slows down the release. Weaker pulses produce less depression determining a larger pool, which in turn, favors faster kinetics. This phenomenon helps determining that in trains of stimuli the average phase is conserved.