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

Ceriani, Federico, Hendry, Aenea, Jeng, Jing‐Yi, Johnson, Stuart L, Stephani, Friederike, Olt, Jennifer, Holley, Matthew C, Mammano, Fabio, Engel, Jutta, Kros, Corné J, Simmons, Dwayne D and Marcotti, Walter (2019) Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells. EMBO Journal. e99839 1-19. ISSN 1460-2075

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Research Centres and Groups: Sussex Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology > QP0431 Senses > QP0448 Special senses > QP0461 Hearing. Physiological acoustics
Depositing User: Corne Kros
Date Deposited: 08 Mar 2019 12:22
Last Modified: 08 Mar 2019 12:23

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Project NameSussex Project NumberFunderFunder Ref
Mechanisms of aminoglyscoside ototoxicity and drug damage repair in sensory hair cells: towards the design of otoprotective strategies.G1025MRC-MEDICAL RESEARCH COUNCILMR/K005561/1