Tagging active neurons by soma-targeted Cal-Light

• Published in: Nature communications Vol. 13; no. 1; p. 7692
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/35; 631/1647/2017/1958; 631/1647/334/1874/345; 631/378/1697/1277; 9/10; Action Potentials - physiology; Animals; Behavior; Calcium; Calcium - metabolism; Cell Body; Circuits; Disease control; Fear conditioning; Gene expression; Hippocampus - physiology; Humanities and Social Sciences; Kainic acid; Light; Marking; Marking and tracking techniques; Mice; multidisciplinary; Neural networks; Neurogenesis; Neurons; Neurons - metabolism; Reporter gene; Science; Science (multidisciplinary); Seizures; Signal to noise ratio; Signs and symptoms; Social behavior; Social factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35406-y

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.