Tagging active neurons by soma-targeted Cal-Light

Jung Ho Hyun, Kenichiro Nagahama, Ho Namkung, Neymi Mignocchi, Seung-Eon Roh, Patrick Hannan, Sarah Krüssel, Chuljung Kwak, Abigail McElroy, Bian Liu, Mingguang Cui, Seunghwan Lee, Dongmin Lee, Richard L. Huganir, Paul F. Worley, Akira Sawa and Hyung-Bae Kwon ()
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Jung Ho Hyun: Johns Hopkins School of Medicine
Kenichiro Nagahama: Johns Hopkins School of Medicine
Ho Namkung: Johns Hopkins School of Medicine
Neymi Mignocchi: Max Planck Florida Institute for Neuroscience
Seung-Eon Roh: Johns Hopkins School of Medicine
Patrick Hannan: Johns Hopkins School of Medicine
Sarah Krüssel: Johns Hopkins School of Medicine
Chuljung Kwak: Johns Hopkins School of Medicine
Abigail McElroy: Johns Hopkins School of Medicine
Bian Liu: Johns Hopkins School of Medicine
Mingguang Cui: Korea University College of Medicine
Seunghwan Lee: Korea University College of Medicine
Dongmin Lee: Korea University College of Medicine
Richard L. Huganir: Johns Hopkins School of Medicine
Paul F. Worley: Johns Hopkins School of Medicine
Akira Sawa: Johns Hopkins School of Medicine
Hyung-Bae Kwon: Johns Hopkins School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35406-y

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