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

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 rh...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-12, Vol.350 (6266), p.1361-1366
Main Authors: Gong, Yiyang, Huang, Cheng, Li, Jin Zhong, Grewe, Benjamin F., Zhang, Yanping, Eismann, Stephan, Schnitzer, Mark J.
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Bioluminescence Resonance Energy Transfer Techniques
Biosensing Techniques
Coding
Dendrites - physiology
Drosophila melanogaster - physiology
Dynamics
Electric potential
Evoked Potentials, Somatosensory
Fluorescence
Fluorescence Resonance Energy Transfer
Green Fluorescent Proteins - chemistry
Green Fluorescent Proteins - genetics
Imaging
Insects
Membranes
Mice
Neurobiology
Neurons
Neurons - physiology
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Rhodopsin - chemistry
Rhodopsin - genetics
Rodents
Smell
Spikes
Voltage
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aab0810