Guest Seminar - Imaging Membrane Potential with Genetically Encoded Indicators
The membrane potential is a key biophysical signal that is central to life. Fluorescent voltage indicators enable the non-invasive optical recording of the cellular membrane potential with high spatial resolution. In this talk, I will introduce a palette of bright and sensitive genetically encoded indicators with their fluorescence intensities modulated by membrane potential via electrochromic Förster resonance energy transfer. These indicators feature a hybrid dye-protein architecture that is constructed via enzyme-mediated site-specific incorporation of a bioorthogonal functional handle into a voltage-sensing rhodopsin, followed by an inverse-electron-demand Diels-Alder cycloaddition to conjugate the fluorescence reporter. These indicators display millisecond response kinetics and enable optical recording of action potentials at over 30 minutes across a large neuronal population. They could also be paired with optogenetic actuators to achieve the all-optical investigation of neuronal physiology.