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

Linda Madisen, Tianyi Mao, Henner Koch, Jia Min Zhuo, Antal Berenyi, Shigeyoshi Fujisawa, Yun Wei A. Hsu, Alfredo J. Garcia, Xuan Gu, Sebastien Zanella, Jolene Kidney, Hong Gu, Yimei Mao, Bryan M. Hooks, Edward S. Boyden, György Buzsáki, Jan Marino Ramirez, Allan R. Jones, Karel Svoboda, Xue HanEric E. Turner, Hongkui Zeng

Research output: Contribution to journalArticlepeer-review

835 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)793-802
Number of pages10
JournalNature Neuroscience
Issue number5
StatePublished - May 2012

ASJC Scopus subject areas

  • Neuroscience(all)


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