@article{fe823e44b07b46908b8bd6c65ea35bc5,
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.",
author = "Linda Madisen and Tianyi Mao and Henner Koch and Zhuo, {Jia Min} and Antal Berenyi and Shigeyoshi Fujisawa and Hsu, {Yun Wei A.} and Garcia, {Alfredo J.} and Xuan Gu and Sebastien Zanella and Jolene Kidney and Hong Gu and Yimei Mao and Hooks, {Bryan M.} and Boyden, {Edward S.} and Gy{\"o}rgy Buzs{\'a}ki and Ramirez, {Jan Marino} and Jones, {Allan R.} and Karel Svoboda and Xue Han and Turner, {Eric E.} and Hongkui Zeng",
note = "Funding Information: We are grateful for the technical support of the Atlas Production Team, led by P. Wohnoutka, and the Technology Team, led by C. Dang, at the Allen Institute. We thank A. Nagy (Mount Sinai Hospital in Toronto) for providing the G4 ES cell line and K. Deisseroth (Stanford University) for providing the eNpHR3.0 construct. The authors wish to thank the Allen Institute founders, P.G. Allen and J. Allen, for their vision, encouragement and support. This work was funded by the Allen Institute for Brain Science and the Howard Hughes Medical Institute, US National Institutes of Health (NIH) grant DA028298 to H.Z., NIH grants MH90478 and MH093667 to E.E.T., NIH grant MH085944 and an Alfred P. Sloan Foundation grant to X.H., NIH grants NS034994 and MH54671 and a US National Science Foundation grant to G.B., and a Marie Curie Fellowship (EU FP7 PEOPLE 2009 IOF 254780) to A.B.",
year = "2012",
month = may,
doi = "10.1038/nn.3078",
language = "English (US)",
volume = "15",
pages = "793--802",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "5",
}