Millisecond-timescale, Genetically Targeted Optical Control of Neural Activity

Nat Neurosci. 2005 Sep;8(9):1263-8. doi: 10.1038/nn1525. Epub 2005 Aug 14.

Abstract

Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Action Potentials / radiation effects*
  • Algal Proteins / chemistry
  • Algal Proteins / genetics
  • Algal Proteins / metabolism
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Electrophysiology / methods*
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Ion Channel Gating / physiology
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Inhibition / radiation effects
  • Neurons / physiology
  • Neurons / radiation effects*
  • Optics and Photonics*
  • Photobiology / methods*
  • Pyridazines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / physiology
  • Reaction Time / radiation effects
  • Reproducibility of Results
  • Rhodopsin / chemistry
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Synaptic Transmission / physiology
  • Synaptic Transmission / radiation effects*
  • Time Factors
  • Transfection

Substances

  • Algal Proteins
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Ion Channels
  • Pyridazines
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Green Fluorescent Proteins
  • Rhodopsin
  • gabazine