Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine‐tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca(2+) signalling in mice in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca(2+) signals originating in OHCs and non‐sensory cells. OHCs fire spontaneous Ca(2+) action potentials during a narrow period of neonatal development. Simultaneously, waves of Ca(2+) activity in the non‐sensory cells of the greater epithelial ridge cause, via ATP‐induced activation of P2X(3) receptors, the increase and synchronization of the Ca(2+) activity in nearby OHCs. This synchronization is required for the refinement of their immature afferent innervation. In the absence of connexin channels, Ca(2+) waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity of OHCs requires experience‐independent Ca(2+) signals from sensory and non‐sensory cells.