The neural crest as a bioelectric Rosetta Stone: translating the analog and digital bioelectric code with Fluorescent Lifetime Imaging (FLIM)

Translating the bioelectric code remains one of the core challenges to widespread biomedical translation of bioelectric interventions, as well as a better evolutionary understanding of how developmental ionic signaling became the basis of neural intelligence. Thus, it is essential to develop model systems and protocols in which diverse bioelectrical parameters can be quantitatively studied together, in the living state, and connected to cell- and tissue-level outcomes. Here, we apply state-of-the-art quantitative Fluorescent Lifetime Imaging (FLIM) optical estimation of membrane potential (Vmemoe) to map the bioelectric dynamics of spreading Xenopus laevis neural crest cells over roughly 18-hour time periods. We identify a slow “analog” bioelectric component that functions on the scale of hours, and a faster “digital” component that acts on the scale of seconds. We then use information theory to show that digital NCC Vmem dynamics are largely distinct from calcium dynamics. Finally, we provide a survey of diverse bioelectric events revealing a deep complexity in collective bioelectric dynamics, likely involving tunneling nanotubes in their transmission, which suggests numerous avenues for further investigation.