Short-term facilitation modulates size and timing of the synaptic response at the inner hair cell ribbon synapse

Inner hair cells (IHCs) in the mammalian cochlea are able to continuously release neurotransmitter in the presence of constant stimuli. Nonetheless, strong synaptic depression is observed over the first few milliseconds of stimulation. This process most likely underlies adaptation in the auditory nerve. In the present study we demonstrate that under certain conditions of stimulation, facilitation can occur at the IHC ribbon synapse. Using simultaneous whole-cell, voltage-clamp recordings from IHCs and afferent fiber endings in excised postnatal rat cochleae, we stimulated IHCs with 2ms long test depolarizations from a holding potential of -89 mV. Synaptic currents in afferent fibers occurred with high failure rates of ~50%. However, when a pre-depolarization to values of -55 to -49 mV was implemented before the test pulse, success rates of the synaptic response increased to 100%, the strength of the synaptic response increased ~2.8-fold, and synaptic latency was reduced by ~50%. When calcium influx was minimized during pre-depolarization, none of these effects were found, suggesting that calcium influx during pre-depolarizations is required for synaptic conditioning. Similarly, in response to paired-pulse protocols, short term facilitation occurred. The response to the second stimulus increased up to~5-fold, and its latency was reduced by up to 35% compared to the response to the first stimulus. We propose that at the IHC resting membrane potential, the ribbon synapse operates in a constantly facilitated mode caused by Ca²⁺ influx, optimizing the size and timing of the postsynaptic response in auditory nerve fibers.