Development and regeneration of hair cells share common functional features

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Abstract
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 Cav3.1 channel is expressed early in development to initiate spontaneous Ca2+ spikes. Cav1.3 currents, typical of mature hair cells, appeared later in development. Moreover, there is a surprising disappearance of the Cav3.1 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 Cav3.1 and the ensuing SAPs are signatures of hair cell development and regeneration.