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

The EMBO Journal
Federico CerianiWalter Marcotti

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.

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Citations

Oct 30, 2019·The Journal of Physiology·Jing-Yi JengWalter Marcotti
Jul 28, 2020·The Journal of Physiology·Jing-Yi JengWalter Marcotti
Oct 15, 2019·ELife·Hiu-Tung C WongKatie Kindt
Jul 14, 2020·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Charmee H MehtaTed A Meyer
Oct 12, 2020·Neuroscience Bulletin·Sasa Jovanovic, Ivan Milenkovic
Nov 6, 2020·The Journal of Physiology·Adam J CarltonWalter Marcotti
May 30, 2021·Proceedings of the National Academy of Sciences of the United States of America·Minwoo Wendy JangByung Yoon Choi
Jun 8, 2021·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Maria MorellRobert E Shadwick
May 29, 2021·The Journal of Physiology·Francesca De FaveriFederico Ceriani
Aug 20, 2021·Current Opinion in Otolaryngology & Head and Neck Surgery·Shuohao SunUlrich Müller
Sep 28, 2021·Frontiers in Neuroscience·Richard D Rabbitt, Holly A Holman

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Methods Mentioned

BETA
genotyping

Key Resources (RRID) Mentioned

SCR_011323
SCR_002815
SCR_014795

Software Mentioned

Python
ImageJ
pCLAMP
Fiji Image
Origin
SIMA

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