Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes

For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca²⁺ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over 20 mV. Ca²⁺ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca²⁺ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca²⁺ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca²⁺ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca²⁺ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs.