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Science. 2015 Dec 11;350(6266):1361-6. doi: 10.1126/science.aab0810. Epub 2015 Nov 19.

High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor.

Author information

1
James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. yiyang.gong@duke.edu mschnitz@stanford.edu.
2
James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
3
James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA.
4
James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
5
James H. Clark Center, Stanford University, Stanford, CA 94305, USA. CNC Program, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. yiyang.gong@duke.edu mschnitz@stanford.edu.

Abstract

Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Previous GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores through resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than previous GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy.

PMID:
26586188
PMCID:
PMC4904846
DOI:
10.1126/science.aab0810
[Indexed for MEDLINE]
Free PMC Article

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