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

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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 Ca(v)3.1 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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2019-01
Language
English
Article Type
Article
Citation

NATURE COMMUNICATIONS, v.10

ISSN
2041-1723
DOI
10.1038/s41467-018-08282-8
URI
http://hdl.handle.net/10203/250380
Appears in Collection
BS-Journal Papers(저널논문)
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