Photoactivated voltage imaging in tissue with an archaerhodopsin-derived reporter

Miao Ping Chien, Daan Brinks, Guilherme Testa-Silva, He Tian, F. Phil Brooks, Yoav Adam, William Bloxham, Benjamin Gmeiner, Simon Kheifets, Adam E. Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
68 Downloads (Pure)


Photoactivated genetically encoded voltage indicators (GEVIs) have the potential to enable optically sectioned voltage imaging at the intersection of a photoactivation beam and an imaging beam. We developed a pooled high-throughput screen to identify archaerhodopsin mutants with enhanced photoactivation. After screening ~105 cells, we identified a novel GEVI, NovArch, whose one-photon near-infrared fluorescence is reversibly enhanced by weak one-photon blue or two-photon near-infrared excitation. Because the photoactivation leads to fluorescent signals catalytically rather than stoichiometrically, high fluorescence signals, optical sectioning, and high time resolution are achieved simultaneously at modest blue or two-photon laser power. We demonstrate applications of the combined molecular and optical tools to optical mapping of membrane voltage in distal dendrites in acute mouse brain slices and in spontaneously active neurons in vivo.

Original languageEnglish
Article numbereabe3216
JournalScience advances
Issue number19
Publication statusPublished - 5 May 2021

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Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).


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