Millisecond-timescale, genetically targeted optical control of neural activity.
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.
Boyden
Edward S
ES
Department of Bioengineering, Stanford University, 318 Campus Drive West, Stanford, California 94305, USA.
Zhang
Feng
F
Bamberg
Ernst
E
Nagel
Georg
G
Deisseroth
Karl
K
D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects*; D020418:Algal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology / Q000528:radiation effects*; D055095:Optics and Photonics; D018462:Photobiology / Q000379:methods*; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D015203:Reproducibility of Results; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology / Q000528:radiation effects*; D013997:Time Factors; D014162:Transfection
D020418:Algal Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007473:Ion Channels; D011724:Pyridazines; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D049452:Green Fluorescent Proteins; D012243:Rhodopsin; C049853:gabazine