A Ca²⁺ level-independent component of recovery from sensory adaptation supports continuous vesicle supply at cochlear hair cell ribbon synapses

Maintenance of synaptic transmission can be accelerated by mechanisms dependent on intracellular Ca 2+ signaling. However, at the first auditory synapse between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea, the process of synaptic vesicle recovery following strong, prolonged stimulation is unclear. To address this, we examined the Ca 2+ -dependence of presynaptic recovery in IHCs with measurements of postsynaptic activity in SGNs while depolarizing the IHC. Following vesicle-depleting stimulation of 1 second duration, SGN postsynaptic responses recovered completely within a few seconds. This process was unperturbed when reducing the intracellular Ca 2+ concentration by changing from 1 to 5 mM EGTA. Thus, synaptic recovery following depleting stimulation at IHC-SGN synapses may differ from the Ca 2+ -dependent process described during and after stimulation over shorter timescales. We propose a Ca 2+ level-insensitive mechanism of recovery at this continuously active sensory synapse to support vesicle release rates of hundreds per second indefatigably.