Genetically encoded probes for optical imaging of brain electrical activity

The combination of optical imaging methods with targeted expression of protein-based fluorescent probes constitutes a powerful approach for functional analysis of selected cell populations within intact neuronal circuitries. Herein, we lay out the conceptual motivation for optogenetic recording of brain electrical activity using genetically encoded voltage-sensitive fluorescent proteins (VSFPs), describe how the current generation of VSFPs has evolved, and demonstrate how VSFPs report membrane voltage signals in isolated cells, brain slices, and living animals. We conclude with a critical appraisal of VSFPs for voltage recording and highlight promising applications of this emerging methodology for bridging cellular and intact systems biology.