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Nat Commun. 2020 Jan 10;11(1):210. doi: 10.1038/s41467-019-14005-4.

Non-invasive optical control of endogenous Ca2+ channels in awake mice.

Author information

1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
2
Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
3
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
4
Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
5
Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
6
Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea. sklee@ibs.re.kr.
7
Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea. shin@ibs.re.kr.
8
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. wondo@kaist.ac.kr.
9
Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea. wondo@kaist.ac.kr.
10
KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. wondo@kaist.ac.kr.

Abstract

Optogenetic approaches for controlling Ca2+ channels provide powerful means for modulating diverse Ca2+-specific biological events in space and time. However, blue light-responsive photoreceptors are, in principle, considered inadequate for deep tissue stimulation unless accompanied by optic fiber insertion. Here, we present an ultra-light-sensitive optogenetic Ca2+ modulator, named monSTIM1 encompassing engineered cryptochrome2 for manipulating Ca2+ signaling in the brain of awake mice through non-invasive light delivery. Activation of monSTIM1 in either excitatory neurons or astrocytes of mice brain is able to induce Ca2+-dependent gene expression without any mechanical damage in the brain. Furthermore, we demonstrate that non-invasive Ca2+ modulation in neurons can be sufficiently and effectively translated into changes in behavioral phenotypes of awake mice.

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