Journal
NATURE NEUROSCIENCE
Volume 15, Issue 5, Pages 793-802Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3078
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Funding
- Allen Institute for Brain Science
- Howard Hughes Medical Institute
- US National Institutes of Health (NIH) [DA028298, MH085944, NS034994, MH54671]
- Alfred P. Sloan Foundation
- US National Science Foundation
- Marie Curie Fellowship
- EU [2009 IOF 254780]
- Directorate For Engineering
- Emerging Frontiers & Multidisciplinary Activities [0835878] Funding Source: National Science Foundation
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1042134] Funding Source: National Science Foundation
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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.
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