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

Nature neuroscience | 2012

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.

Pubmed ID: 22446880 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: MH54671
  • Agency: NIDA NIH HHS, United States
    Id: DA028298
  • Agency: NIMH NIH HHS, United States
    Id: MH093667
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIMH NIH HHS, United States
    Id: MH90478
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH054671
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS034994
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH090478
  • Agency: NIMH NIH HHS, United States
    Id: MH085944
  • Agency: NINDS NIH HHS, United States
    Id: NS034994
  • Agency: NIMH NIH HHS, United States
    Id: K99 MH085944
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA028298
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA028298-02
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH093667
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL107084
  • Agency: NIMH NIH HHS, United States
    Id: R00 MH085944

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