Development and regeneration of hair cells share common functional features

The structural phenotype of neural connections in the auditory brainstem is sculpted by spontaneous and stimulus-induced neural activities during development. However, functional and molecular mechanisms of spontaneous action potentials (SAPs) in the developing cochlea are unknown. Additionally, it is unclear how regenerating hair cells establish their neural ranking in the constellation of neurons in the brainstem. We have demonstrated that a transient Ca²⁺ current produced by the Ca_v3.1 channel is expressed early in development to initiate spontaneous Ca²⁺ spikes. Ca _v1.3 currents, typical of mature hair cells, appeared later in development. Moreover, there is a surprising disappearance of the Ca _v3.1 current that coincides with the attenuation of the transient Ca²⁺ current as the electrical properties of hair cells transition to the mature phenotype. Remarkably, this process is recapitulated during hair-cell regeneration, suggesting that the transient expression of Ca _v3.1 and the ensuing SAPs are signatures of hair cell development and regeneration.