PT  - JOURNAL ARTICLE
AU  - Xiaoyu Lu
AU  - Yunmiao Wang
AU  - Zhuohe Liu
AU  - Yueyang Gou
AU  - Dieter Jaeger
AU  - François St-Pierre
TI  - Detecting rapid pan-cortical voltage dynamics in vivo with a brighter and faster voltage indicator
AID  - 10.1101/2022.08.29.505018
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.29.505018
4099  - http://biorxiv.org/content/early/2022/08/31/2022.08.29.505018.short
4100  - http://biorxiv.org/content/early/2022/08/31/2022.08.29.505018.full
AB  - Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the slow kinetics of current GEVIs limit their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator whose performance is improved for all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in mice. We also developed an approach to effectively correct optical measurements from hemodynamic and motion artifacts. Finally, we achieved stable brain-wide voltage imaging and successfully tracked gamma-frequency whisker and visual stimulations in awake mice in single trials, opening the door to investigating the role of high-frequency signals in brain computations.Competing Interest StatementFSP holds a US patent for a voltage sensor design (patent #US9606100 B2).