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J. Mol. Biol., Volume 432, Issue 4, 14 February 2020, Pages 815-827 | https://doi.org/10.1016/j.jmb.2020.01.010 Optogenetic Modulation of TrkB Signaling in the Mouse Brain

Jongryul Hong¹, Won Do Heo^1,2,3,*

¹Department of Biological Science, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Republic of Korea
²Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, 305-701, Republic of Korea
³KAIST Institute for the BioCentury, KAIST, Daejeon, 305-701, Republic of Korea

^*Corresponding author

Abstract

Optogenetic activation of receptors has advantages compared with chemical or ligand treatment because of its high spatial and temporal precision. Especially in the brain, the use of a genetically encoded light-tunable receptor is superior to direct infusion or systemic drug treatment. We applied light-activatable TrkB receptors in the mouse brain with reduced basal activity by incorporating Cry2PHR mutant, Opto-cytTrkB(E281A). Upon AAV mediated gene delivery, this form was expressed at sufficient levels in the mouse hippocampus (HPC) and medial entorhinal cortex (MEC) retaining normal canonical signal transduction by the blue light stimulus, even by delivery of noninvasive LED light on the mouse head. Within target cells, where its expression was driven by a cell type-specific promoter, Opto-cytTrkB(E281A)-mediated TrkB signaling could be controlled by adjusting light-stimulating conditions. We further demonstrated that Opto-cytTrkB(E281A) could locally induce TrkB signaling in axon terminals in the MEC-HPC. In summary, Opto-cytTrkB(E281A) will be useful for elucidating time- and region-specific roles of TrkB signaling ranging from cellular function to neural circuit mechanisms.

Keywords : optogenetics; Ntrk2; BDNF; TrkB; Cry2PHR

논문정보

형식Research article
게재일2020년 02월 (BRIC 등록일 2020-09-08)
연구진국내 연구진
분야 생명과학 > 세포생물학
구분구・추천논문

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