title: Selective photostimulation of genetically chARGed neurons.
abstract: To permit direct functional analyses of neural circuits, we have developed a method for stimulating groups of genetically designated neurons optically. Coexpression of the Drosophila photoreceptor genes encoding arrestin-2, rhodopsin (formed by liganding opsin with retinal), and the alpha subunit of the cognate heterotrimeric G protein--an explosive combination we term "chARGe"--sensitizes generalist vertebrate neurons to light. Illumination of a mixed population of neurons elicits action potentials selectively and cell-autonomously in its genetically chARGed members. In contrast to bath-applied photostimulants or caged neurotransmitters, which act indiscriminately throughout the illuminated volume, chARGe localizes the responsiveness to light. Distributed activity may thus be fed directly into a circumscribed population of neurons in intact tissue, irrespective of the spatial arrangement of its elements.
authors.affiliation: Laboratory of Neural Systems, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Zemelman
authors.forename: Georgia A
authors.initials: GA
authors.lastname: Lee
authors.forename: Minna
authors.initials: M
authors.lastname: Ng
authors.forename: Gero
authors.initials: G
authors.lastname: Miesenböck
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism*; D009865:Oocytes; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012172:Retinaldehyde / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014785:Vision, Ocular / Q000235:genetics*; D014981:Xenopus
chemical_list: C504666:Arr2 protein, Drosophila; D019390:Arrestins; D029721:Drosophila Proteins; D005136:Eye Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C083315:ninaE protein, Drosophila; D012243:Rhodopsin; D019204:GTP-Binding Proteins; D012172:Retinaldehyde