In vivo spontaneous Ca2+ activity in the pre-hearing mammalian cochlea

The refinement of neural circuits towards mature function is driven during development by patterned spontaneous calcium-dependent electrical activity. In the auditory system, this sensory-independent activity arises in the pre-hearing cochlea and regulates the survival and refinement of the auditory pathway. However, the origin and interplay of calcium signals during cochlear development is unknown in vivo. Here we show how calcium dynamics in the cochlear neuroepithelium of live pre-hearing mice shape the activity of the inner hair cells (IHCs) and their afferent synapses. Both IHCs and supporting cells (SCs) generate spontaneous calcium-dependent activity. Calcium waves from SCs synchronise the activity of nearby IHCs, which then spreads longitudinally recruiting several additional IHCs via a calcium wave-independent mechanism. This synchronised IHC activity in vivo increases the probability of afferent terminal recruitment. Moreover, the modiolar-to-pillar segregation in sound sensitivity of mature auditory nerve fibres appears to be primed at pre-hearing ages.