Bioelectric Burst Characteristics and Coupling within the Somatic Epithelium–Blastema Circuit Dynamically Relate to Regenerative Stalling during Adult Limb Repair

Abstract Background Transient bursts of exaggerated mid-frequency bioelectric activity in the limb blastema are thought to impede organized tissue regrowth. However, no study has examined burst characteristics and coupling across the somatic epithelium–blastema circuit or linked them to continuous measurements of outgrowth kinetics. Objective We sought to (1) define the features of epithelial and blastemal bioelectric bursts during unrestricted limb use, (2) determine how reliably blastemal bursts can be inferred from epithelial recordings, and (3) relate burst metrics to real-time indices of regenerative velocity obtained with optical displacement sensors. Methods We analyzed 1,046 h of wirelessly streamed bilateral epithelial and blastemal voltage recordings from five adult salamanders undergoing limb regeneration, concurrent with high-frequency measurements of stump-tip extension. Results Blastemal bursts were longer than epithelial bursts and showed shorter inter-burst intervals. Long bursts (>200 ms) in both compartments exhibited substantial temporal overlap (>30%), with epithelial bursts tending to precede blastemal burst onset by 8 ms. Declining extension velocity correlated with increased epithelial burst rates and durations, whereas analogous blastemal burst parameters predicted enhanced outgrowth. Conclusion Epithelial bioelectric bursts typically lead blastemal bursts by only a few milliseconds, and their prevalence is linked to regenerative stalling in freely moving animals. These findings highlight the epithelium as a proximal bioelectric driver of impaired morphogenesis and suggest that selective modulation of epithelial bursting may restore normal regenerative kinetics.