title: A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing.
abstract: Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes mediated Cre-dependent, robust activation or silencing of cortical pyramidal neurons in vitro and in vivo upon light stimulation, with ChR2-EYFP and Arch-ER2 demonstrating light sensitivity approaching that of in utero or virally transduced neurons. We further show specific photoactivation of parvalbumin-positive interneurons in behaving ChR2-EYFP reporter mice. The robust, consistent and inducible nature of our ChR2 mice represents a significant advance over previous lines, and the Arch-ER2 and eNpHR3.0 mice are to our knowledge the first demonstration of successful conditional transgenic optogenetic silencing. When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy.
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Madisen
authors.forename: Tianyi
authors.initials: T
authors.lastname: Mao
authors.forename: Henner
authors.initials: H
authors.lastname: Koch
authors.forename: Jia-min
authors.initials: JM
authors.lastname: Zhuo
authors.forename: Antal
authors.initials: A
authors.lastname: Berenyi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Yun-Wei A
authors.initials: YW
authors.lastname: Hsu
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Garcia
authors.forename: Xuan
authors.initials: X
authors.lastname: Gu
authors.forename: Sebastien
authors.initials: S
authors.lastname: Zanella
authors.forename: Jolene
authors.initials: J
authors.lastname: Kidney
authors.forename: Hong
authors.initials: H
authors.lastname: Gu
authors.forename: Yimei
authors.initials: Y
authors.lastname: Mao
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Hooks
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.forename: György
authors.initials: G
authors.lastname: Buzsáki
authors.forename: Jan Marino
authors.initials: JM
authors.lastname: Ramirez
authors.forename: Allan R
authors.initials: AR
authors.lastname: Jones
authors.forename: Karel
authors.initials: K
authors.lastname: Svoboda
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Eric E
authors.initials: EE
authors.lastname: Turner
authors.forename: Hongkui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019843:Archaeal Proteins; D001921:Brain / Q000166:cytology*; D000075402:Channelrhodopsins; D018274:Electroporation / Q000379:methods; D025602:Halorhodopsins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D055095:Optics and Photonics; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D014851:Wakefulness; D017494:Proton Pumps
chemical_list: D019843:Archaeal Proteins; D000075402:Channelrhodopsins; D025602:Halorhodopsins; D019426:Integrases; D008164:Luminescent Proteins; D011506:Proteins; D022661:RNA, Untranslated; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C055476:archaerhodopsin protein, Archaea; D017494:Proton Pumps; C045073:Cre recombinase