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, Hyung Bae Kwon

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Article number7692
JournalNature communications
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology


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