Concurrent maturation of inner hair cell synaptic Ca²⁺ influx and auditory nerve spontaneous activity around hearing onset in mice

Hearing over a wide range of sound intensities is thought to require complementary coding by functionally diverse spiral ganglion neurons (SGNs), each changing activity only over a subrange. The foundations of SGN diversity are not well understood but likely include differences among their inputs: the presynaptic active zones (AZs) of inner hair cells (IHCs). Here we studied one candidate mechanism for causing SGN diversity- heterogeneity of Ca²⁺ influx among the AZs of IHCs- during postnatal development of the mouse cochlea. Ca ²⁺ imaging revealed a change from regenerative to graded synaptic Ca²⁺ signaling after the onset of hearing, when in vivo SGN spike timing changed from patterned to Poissonian. Furthermore, we detected the concurrent emergence of stronger synaptic Ca²⁺ signals in IHCs and higher spontaneous spike rates in SGNs. The strengthening of Ca²⁺ signaling at a subset of AZs primarily reflected a gain of Ca²⁺ channels. We hypothesize that the number of Ca²⁺ channels at each IHC AZ critically determines the firing properties of its corresponding SGN and propose that AZ heterogeneity enables IHCs to decompose auditory information into functionally diverse SGNs.