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Detecting rapid pan-cortical voltage dynamics in vivo with a brighter and faster voltage indicator

View ORCID ProfileXiaoyu Lu, View ORCID ProfileYunmiao Wang, View ORCID ProfileZhuohe Liu, View ORCID ProfileYueyang Gou, View ORCID ProfileDieter Jaeger, View ORCID ProfileFrançois St-Pierre
doi: https://doi.org/10.1101/2022.08.29.505018
Xiaoyu Lu
1Systems, Synthetic, and Physical Biology Program, Rice University, Houston, Texas, 77005, USA
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Yunmiao Wang
2Neuroscience Graduate Program, Emory University, Atlanta, Georgia, 30322, USA
3Biology Department, Emory University, Atlanta, Georgia, 30322, USA
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Zhuohe Liu
4Department of Electrical and Computer Engineering, Rice University, Houston, Texas, 77005, USA
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Yueyang Gou
5Department of Neuroscience, Baylor College of Medicine, Houston, Texas, 77030, USA
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Dieter Jaeger
3Biology Department, Emory University, Atlanta, Georgia, 30322, USA
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  • For correspondence: djaeger@emory.edu stpierre@bcm.edu
François St-Pierre
1Systems, Synthetic, and Physical Biology Program, Rice University, Houston, Texas, 77005, USA
4Department of Electrical and Computer Engineering, Rice University, Houston, Texas, 77005, USA
5Department of Neuroscience, Baylor College of Medicine, Houston, Texas, 77030, USA
6Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA
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  • For correspondence: djaeger@emory.edu stpierre@bcm.edu
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Abstract

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 Statement

FSP holds a US patent for a voltage sensor design (patent #US9606100 B2).

Footnotes

  • ↵# These authors have jointly supervised the work

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 31, 2022.
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Detecting rapid pan-cortical voltage dynamics in vivo with a brighter and faster voltage indicator
Xiaoyu Lu, Yunmiao Wang, Zhuohe Liu, Yueyang Gou, Dieter Jaeger, François St-Pierre
bioRxiv 2022.08.29.505018; doi: https://doi.org/10.1101/2022.08.29.505018
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Detecting rapid pan-cortical voltage dynamics in vivo with a brighter and faster voltage indicator
Xiaoyu Lu, Yunmiao Wang, Zhuohe Liu, Yueyang Gou, Dieter Jaeger, François St-Pierre
bioRxiv 2022.08.29.505018; doi: https://doi.org/10.1101/2022.08.29.505018

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