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

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Science  11 Dec 2015:
Vol. 350, Issue 6266, pp. 1361-1366
DOI: 10.1126/science.aab0810

In vivo imaging of neuronal voltage spikes

Neuroscientists have long sought tools that allow optical imaging of individual neurons' membrane voltage dynamics in awake behaving animals. Gong et al. genetically engineered a protein voltage indicator that can report action potentials with <1-ms precision and orders of magnitude lower spike detection error rates than were previously possible. They were thus able to record action potentials and membrane voltage dynamics in the brains of awake mice and fruit flies.

Science, this issue p. 1361


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.

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