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

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.

Source: EMBO Journal - April 24, 2019 Category: Molecular Biology Authors: Ceriani, F., Hendry, A., Jeng, J.-Y., Johnson, S. L., Stephani, F., Olt, J., Holley, M. C., Mammano, F., Engel, J., Kros, C. J., Simmons, D. D., Marcotti, W. Tags: Development & Differentiation, Membrane & Intracellular Transport Articles Source Type: research