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- Title
Tagging active neurons by soma-targeted Cal-Light.
- Authors
Hyun, Jung Ho; Nagahama, Kenichiro; Namkung, Ho; Mignocchi, Neymi; Roh, Seung-Eon; Hannan, Patrick; Krüssel, Sarah; Kwak, Chuljung; McElroy, Abigail; Liu, Bian; Cui, Mingguang; Lee, Seunghwan; Lee, Dongmin; Huganir, Richard L.; Worley, Paul F.; Sawa, Akira; Kwon, Hyung-Bae
- 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. Techniques for tagging active neurons with high spatiotemporal precision are limited. Here the authors report soma-targeted CalLight (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression, and generate a conditional ST-Cal-Light knock-in mouse.
- Subjects
ACTION potentials; NEURONS; REPORTER genes; NEURAL circuitry; GENE expression
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35406-y