Bright and photostable chemigenetic indicators for extended in vivo voltage imaging

Ahmed S. Abdelfattah, Takashi Kawashima, Amrita Singh, Ondrej Novak, Hui Liu, Yichun Shuai, Yi Chieh Huang, Luke Campagnola, Stephanie C. Seeman, Jianing Yu, Jihong Zheng, Jonathan B. Grimm, Ronak Patel, Johannes Friedrich, Brett D. Mensh, Liam Paninski, John J. Macklin, Gabe J. Murphy, Kaspar Podgorski, Bei Jung LinTsai Wen Chen, Glenn C. Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B. Ahrens, Luke D. Lavis, Eric R. Schreiter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

Abstract

Genetically encoded voltage indicators (GEVIs) enable monitoring of neuronal activity at high spatial and temporal resolution. However, the utility of existing GEVIs has been limited by the brightness and photostability of fluorescent proteins and rhodopsins. We engineered a GEVI, called Voltron, that uses bright and photostable synthetic dyes instead of protein-based fluorophores, thereby extending the number of neurons imaged simultaneously in vivo by a factor of 10 and enabling imaging for significantly longer durations relative to existing GEVIs. We used Voltron for in vivo voltage imaging in mice, zebrafish, and fruit flies. In the mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously over a 15-minute period of continuous imaging. In larval zebrafish, Voltron enabled the precise correlation of spike timing with behavior.

Original languageEnglish
Pages (from-to)699-704
Number of pages6
JournalScience
Volume365
Issue number6454
DOIs
StatePublished - 16 Aug 2019

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