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.

Allen Institute for Brain Science Seattle WA 98109 USA

Center for Computational Biology Flatiron Institute New York NY 10010 USA

Department of Auditory Neuroscience Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

Department of Neuroscience and Grossman Center for the Statistics of Mind Columbia University New York NY 10027 USA

Department of Statistics and Center for Theoretical Neuroscience Columbia University New York NY 10027 USA

Institute of Neuroscience National Yang Ming University Taipei 112 Taiwan

Janelia Research Campus Howard Hughes Medical Institute Ashburn VA 20147 USA

Solomon H Snyder Department of Neuroscience Johns Hopkins University Baltimore MD 21205 USA

Nat Methods. 2019 Nov;16(11):1076. doi: 10.1038/s41592-019-0653-y. PubMed

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