Functional development and regeneration of hair cells in the zebrafish lateral line

Hair cells are mechanosensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. Different from mammals, the hair cells of lower vertebrates, including those present in the neuromasts of the zebrafish lateral line, regenerate following environmental or chemical insults. Here we investigate the time-course of regeneration of hair cells in vivo using electrophysiology, 2-photon imaging and immunostaining applied to wild-type and genetically-encoded fluorescent indicator zebrafish lines. Functional hair cells drive spontaneous action potentials in the posterior lateral line afferent fibres, the frequency of which progressively increases over the first 10-days post-fertilization (dpf). Higher firing-rate fibres are only observed from ~6 dpf. Following copper treatment, newly formed hair cells become functional and are able to drive APs in the afferent fibres within 48 hours in both early-larval (≤8 dpf) and late-larval (12-17 dpf) zebrafish. However, the complete functional regeneration of the entire neuromast is delayed in late-larval compared to early-larval zebrafish. We propose that while individual regenerating hair cells can rapidly become active, the acquisition of fully functional neuromasts progresses faster at early-larval stages, a time when hair cells are still under development. At both ages, the afferent terminals in the regenerating neuromast appear to make initial contact with supporting cells. The ablation of the lateral line afferent neurons prevents the timely regeneration of supporting cells and hair cells. These findings indicate that the afferent system is likely to facilitate or promote the neuromast regeneration process.