Remote control of neuronal activity with a light-gated glutamate receptor.
The ability to stimulate select neurons in isolated tissue and in living animals is important for investigating their role in circuits and behavior. We show that the engineered light-gated ionotropic glutamate receptor (LiGluR), when introduced into neurons, enables remote control of their activity. Trains of action potentials are optimally evoked and extinguished by 380 nm and 500 nm light, respectively, while intermediate wavelengths provide graded control over the amplitude of depolarization. Light pulses of 1-5 ms in duration at approximately 380 nm trigger precisely timed action potentials and EPSP-like responses or can evoke sustained depolarizations that persist for minutes in the dark until extinguished by a short pulse of approximately 500 nm light. When introduced into sensory neurons in zebrafish larvae, activation of LiGluR reversibly blocks the escape response to touch. Our studies show that LiGluR provides robust control over neuronal activity, enabling the dissection and manipulation of neural circuitry in vivo.
Szobota
Stephanie
S
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Gorostiza
Pau
P
Del Bene
Filippo
F
Wyart
Claire
C
Fortin
Doris L
DL
Kolstad
Kathleen D
KD
Tulyathan
Orapim
O
Volgraf
Matthew
M
Numano
Rika
R
Aaron
Holly L
HL
Scott
Ethan K
EK
Kramer
Richard H
RH
Flannery
John
J
Baier
Herwig
H
Trauner
Dirk
D
Isacoff
Ehud Y
EY
D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology; D007814:Larva; D007930:Leucine / Q000235:genetics; D008029:Lighting / Q000379:methods*; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D018092:Kainic Acid Receptors / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods; D015027:Zebrafish; D000097806:GluK2 Kainate Receptor
D003545:Cysteine; D007930:Leucine; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor