2. Academic Validation
  3. Bright and photostable chemigenetic indicators for extended in vivo voltage imaging

Bright and photostable chemigenetic indicators for extended in vivo voltage imaging

  • Science. 2019 Aug 16;365(6454):699-704. doi: 10.1126/science.aav6416.
Ahmed S Abdelfattah 1,  Takashi Kawashima 1,  Amrita Singh 1 2,  Ondrej Novak 1 3,  Hui Liu 1,  Yichun Shuai 1,  Yi-Chieh Huang 4,  Luke Campagnola 5,  Stephanie C Seeman 5,  Jianing Yu 1,  Jihong Zheng 1,  Jonathan B Grimm 1,  Ronak Patel 1,  Johannes Friedrich 6 7 8,  Brett D Mensh 1,  Liam Paninski 6 7,  John J Macklin 1,  Gabe J Murphy 5,  Kaspar Podgorski 1,  Bei-Jung Lin 4,  Tsai-Wen Chen 4,  Glenn C Turner 1,  Zhe Liu 1,  Minoru Koyama 1,  Karel Svoboda 1,  Misha B Ahrens 1,  Luke D Lavis 1,  Eric R Schreiter 9
Affiliations

Affiliations

  • 1 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
  • 2 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
  • 3 Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
  • 4 Institute of Neuroscience, National Yang-Ming University, Taipei 112, Taiwan.
  • 5 Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • 6 Department of Statistics and Center for Theoretical Neuroscience, Columbia University, New York, NY 10027, USA.
  • 7 Department of Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA.
  • 8 Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
  • 9 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. schreitere@janelia.hhmi.org.
PMID: 31371562 DOI: 10.1126/science.aav6416
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.

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