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 Ca²⁺ 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 Ca²⁺ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca²⁺ action potentials during a narrow period of neonatal development. Simultaneously, waves of Ca²⁺ activity in the non-sensory cells of the greater epithelial ridge cause, via ATP-induced activation of P2X₃ receptors, the increase and synchronization of the Ca²⁺ activity in nearby OHCs. This synchronization is required for the refinement of their immature afferent innervation. In the absence of connexin channels, Ca²⁺ 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 Ca²⁺ signals from sensory and non-sensory cells.

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