Recent Development of Chemigenetic Hybrid Voltage Indicators Enabled by Bioconjugation Chemistry

Fluorescent voltage indicators enable the optical recording of electrophysiology across large cell populations with subcellular resolution; however, their application is often constrained by a limited photon budget. To address this limitation, advanced bioconjugation methods have been employed to site-specifically attach bright and photostable organic dyes to cell-specific protein scaffolds in live cells. The resulting chemigenetic hybrid voltage indicators enable sustained monitoring of voltage fluctuations with an exceptional signal-to-noise ratio, both in vitro and in vivo. This Viewpoint discusses recent advancements in the development of these indicators through bioconjugation chemistry.