Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions

Hyunjin Jung, Seong-Wook Kim, Minsoo Kim, Jongryul Hong, Daseuli Yu, Ji Hye Kim, Yunju Lee, Sungsoo Kim, Doyeon Woo, Hee-Sup Shin, Byung Ouk Park () and Won Do Heo ()
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Hyunjin Jung: Korea Advanced Institute of Science and Technology (KAIST)
Seong-Wook Kim: Institute for Basic Science (IBS)
Minsoo Kim: Institute for Basic Science (IBS)
Jongryul Hong: Korea Advanced Institute of Science and Technology (KAIST)
Daseuli Yu: Korea Advanced Institute of Science and Technology (KAIST)
Ji Hye Kim: Institute for Basic Science (IBS)
Yunju Lee: Institute for Basic Science (IBS)
Sungsoo Kim: Korea Advanced Institute of Science and Technology (KAIST)
Doyeon Woo: Institute for Basic Science (IBS)
Hee-Sup Shin: Institute for Basic Science (IBS)
Byung Ouk Park: Institute for Basic Science (IBS)
Won Do Heo: Korea Advanced Institute of Science and Technology (KAIST)

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Spatiotemporal control of gene expression or labeling is a valuable strategy for identifying functions of genes within complex neural circuits. Here, we develop a highly light-sensitive and efficient photoactivatable Flp recombinase (PA-Flp) that is suitable for genetic manipulation in vivo. The highly light-sensitive property of PA-Flp is ideal for activation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. In addition, PA-Flp can be extended to the Cre-lox system through a viral vector as Flp-dependent Cre expression platform, thereby activating both Flp and Cre. Finally, we demonstrate that PA-Flp–dependent, Cre-mediated Cav3.1 silencing in the medial septum increases object-exploration behavior in mice. Thus, PA-Flp is a noninvasive, highly efficient, and easy-to-use optogenetic module that offers a side-effect-free and expandable genetic manipulation tool for neuroscience research.

Date: 2019
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DOI: 10.1038/s41467-018-08282-8

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