A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing

Madisen, L., Mao, T., Koch, H., Zhuo, J.-m., Berenyi, A., Fujisawa, S., Hsu, Y.-W., Garcia, A. J., Gu, X., Zanella, S., Kidney, J., Gu, H., Mao, Y., Hooks, B. M., Boyden, E. S., Buzsáki, G., Ramirez, J. M., Jones, A. R., Svoboda, K., Han, X., Turner, E. E., Zeng, H. (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing, Nature Neuroscience 15(5):793-802.

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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.

Project

Optogenetics: molecules enabling neural control by light

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