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

EMBO J. 2019 May 2;38(9):e99839. doi: 10.15252/embj.201899839. Epub 2019 Feb 25.

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.

Keywords: calcium waves; hair cells; pre‐hearing development; purinergic receptors; spontaneous activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Afferent Pathways*
  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / physiology*
  • Calcium Signaling
  • Cochlea / physiology*
  • Connexin 30 / physiology*
  • Hair Cells, Auditory, Outer / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Purinergic P2X3 / physiology
  • Sensory Receptor Cells / physiology*
  • Synapses / physiology

Substances

  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Connexin 30
  • Gjb6 protein, mouse
  • Receptors, Purinergic P2X3
  • Calcium