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


ABSTRACT: 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.

SUBMITTER: Ceriani F 

PROVIDER: S-EPMC6484507 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Ceriani Federico F   Hendry Aenea A   Jeng Jing-Yi JY   Johnson Stuart L SL   Stephani Friederike F   Olt Jennifer J   Holley Matthew C MC   Mammano Fabio F   Engel Jutta J   Kros Corné J CJ   Simmons Dwayne D DD   Marcotti Walter W  

The EMBO journal 20190225 9


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<sup>2+</sup> signalling in mice <i>in vivo,</i> through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca<sup>2+</sup> signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca<sup>2+</s  ...[more]

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