한빛사논문
- 조회203
Jung Ho Hyun1,2,10,11, Kenichiro Nagahama1,11, Ho Namkung3,11, Neymi Mignocchi2, Seung-Eon Roh1, Patrick Hannan1,2, Sarah Krüssel1,2, Chuljung Kwak1, Abigail McElroy1, Bian Liu1, Mingguang Cui4,5, Seunghwan Lee4,5, Dongmin Lee4,5, Richard L. Huganir1, Paul F. Worley1, Akira Sawa1,3,6,7,8,9 & Hyung-Bae Kwon1,2,3
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
2Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
3Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
4Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
5BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
6Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
7Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
8Department of Pharmacology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
9Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21025, USA.
10Present address: Department of Brain Sciences, DGIST, Daegu, Republic of Korea.
11These authors contributed equally: Jung Ho Hyun, Kenichiro Nagahama, Ho Namkung
Corresponding author: Correspondence to Hyung-Bae Kwon.
Abstract
Verifying causal effects of neural circuits is essential for proving a direct circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we develop the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, lever-pressing choice behavior, and social interaction behaviors. We also target kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppress seizure symptoms, suggesting ST-Cal-Light's applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-02-21)
- 국내+국외 연구진
- 생명과학 > 신경생물학
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