TY - JOUR T1 - Spontaneous and coordinated Ca<sup>2+</sup> activity of cochlear sensory and non-sensory cells drives the maturation of OHC afferent innervation JF - bioRxiv DO - 10.1101/317172 SP - 317172 AU - Federico Ceriani AU - Aenea Hendry AU - Jing-Yi Jeng AU - Stuart L. Johnson AU - Jennifer Olt AU - Matthew C. Holley AU - Fabio Mammano AU - Corné J. Kros AU - Dwayne D. Simmons AU - Walter Marcotti Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/08/317172.abstract N2 - 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 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+ spikes during a narrow period of immature development. Simultaneously, waves of Ca2+ activity in the non-sensory greater epithelial ridge act, via ATP-induced activation of P2X receptors, to synchronize OHC firing, resulting in the refinement of their 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 in OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells. ER -