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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, Jonathan B. Grimm, Ronak Patel, Johannes Friedrich, Brett D. Mensh, Liam Paninski, John J. Macklin, Kaspar Podgorski, Bei-Jung Lin, Tsai-Wen Chen, Glenn C. Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B. Ahrens, Luke D. Lavis, Eric R. Schreiter
doi: https://doi.org/10.1101/436840
Ahmed S. Abdelfattah
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Takashi Kawashima
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Amrita Singh
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
2The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University, 725 N. Wolfe Street, Baltimore, MD 21205
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Ondrej Novak
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
3Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
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Hui Liu
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Yichun Shuai
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Yi-Chieh Huang
4Institute of Neuroscience, National Yang-Ming University, Taipei, 112 Taiwan
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Jonathan B. Grimm
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Ronak Patel
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Johannes Friedrich
5Department of Statistics and Center for Theoretical Neuroscience, Columbia University, 3227 Broadway, New York, NY 10027
6Department of Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, 3227 Broadway, New York, NY 10027
7Center for Computational Biology, Flatiron Institute, 162 5th Ave, New York, NY 10010
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Brett D. Mensh
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Liam Paninski
5Department of Statistics and Center for Theoretical Neuroscience, Columbia University, 3227 Broadway, New York, NY 10027
6Department of Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, 3227 Broadway, New York, NY 10027
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John J. Macklin
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Kaspar Podgorski
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Bei-Jung Lin
4Institute of Neuroscience, National Yang-Ming University, Taipei, 112 Taiwan
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Tsai-Wen Chen
4Institute of Neuroscience, National Yang-Ming University, Taipei, 112 Taiwan
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Glenn C. Turner
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Zhe Liu
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Minoru Koyama
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Karel Svoboda
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Misha B. Ahrens
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Luke D. Lavis
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Eric R. Schreiter
1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia, USA 20147
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Abstract

Imaging changes in membrane potential using genetically encoded fluorescent voltage indicators (GEVIs) has great potential for monitoring neuronal activity with high spatial and temporal resolution. Brightness and photostability of fluorescent proteins and rhodopsins have limited the utility of existing GEVIs. We engineered a novel GEVI, ‘Voltron’, that utilizes bright and photostable synthetic dyes instead of protein-based fluorophores, extending the combined duration of imaging and number of neurons imaged simultaneously by more than tenfold relative to existing GEVIs. We used Voltron for in vivo voltage imaging in mice, zebrafish, and fruit flies. In mouse cortex, Voltron allowed single-trial recording of spikes and subthreshold voltage signals from dozens of neurons simultaneously, over 15 minutes of continuous imaging. In larval zebrafish, Voltron enabled the precise correlation of spike timing with behavior.

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Posted October 06, 2018.
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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, Jonathan B. Grimm, Ronak Patel, Johannes Friedrich, Brett D. Mensh, Liam Paninski, John J. Macklin, Kaspar Podgorski, Bei-Jung Lin, Tsai-Wen Chen, Glenn C. Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B. Ahrens, Luke D. Lavis, Eric R. Schreiter
bioRxiv 436840; doi: https://doi.org/10.1101/436840
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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, Jonathan B. Grimm, Ronak Patel, Johannes Friedrich, Brett D. Mensh, Liam Paninski, John J. Macklin, Kaspar Podgorski, Bei-Jung Lin, Tsai-Wen Chen, Glenn C. Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B. Ahrens, Luke D. Lavis, Eric R. Schreiter
bioRxiv 436840; doi: https://doi.org/10.1101/436840

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