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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials*
  • Animals
  • Bioluminescence Resonance Energy Transfer Techniques*
  • Biosensing Techniques*
  • Dendrites / physiology
  • Drosophila melanogaster / physiology
  • Evoked Potentials, Somatosensory*
  • Fluorescence Resonance Energy Transfer*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Mice
  • Neurons / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Rhodopsin / chemistry
  • Rhodopsin / genetics
  • Smell

Substances

  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Rhodopsin