Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.

Cochlear 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 Ca 2+ activity in both sensory and non-sensory cells. Calcium signalling 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 Ca 2+ activity and afferent connectivity during development. Using a genetically encoded Ca 2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm +/+ ) and Ocm knockout (Ocm -/- ) littermates, we found increased spontaneous Ca 2+ activity and upregulation of purinergic receptors in OHCs from 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 fibres on Ocm -/- OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca 2+ signalling in the developing cochlea and the maturation of OHC afferent innervation. KEY POINTS: Cochlear outer hair cells (OHCs) exhibit spontaneous Ca 2+ activity during a narrow period of neonatal development. OHC afferent maturation and connectivity requires spontaneous Ca 2+ activity. Oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein, modulates Ca 2+ signals in immature OHCs. Using transgenic mice that endogenously expressed a Ca 2+ sensor, GCaMP6s, we found increased spontaneous Ca 2+ activity and upregulated purinergic receptors in Ocm -/- OHCs. The maturation of afferent synapses in Ocm -/- OHCs was also delayed, leading to an upregulation of ribbon synapses and afferent fibres in Ocm -/- OHCs before hearing onset. We propose that OCM plays an important role in modulating Ca 2+ activity, expression of Ca 2+ channels and afferent innervation in developing OHCs.