Oncomodulin Regulates Spontaneous Calcium Signaling and Maturation of Afferent Innervation in Cochlear Outer Hair Cells

Abstract

AbstractCochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+activity in both sensory and non-sensory cells. Calcium signaling in neonatal OHCs can be modulated by Oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+activity and afferent connectivity during development. Using a genetically encoded Ca2+sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+) and Ocm knockout (Ocm-/-) littermates, we found increased spontaneous Ca2+activity and upregulation of purinergic receptors in OHCs from GCaMP6s Ocm-/-cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibers on GCaMP6s Ocm-/-OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+signaling in the developing cochlea and the maturation of OHC afferent innervation.