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Tagging active neurons by soma-targeted Cal-Light.

Jung Ho HyunKenichiro NagahamaHo NamkungNeymi MignocchiSeung-Eon RohPatrick HannanSarah KruesselChuljung KwakAbigail McElroyBian LiuMingguang CuiSeunghwan LeeDongmin LeeRichard L HuganirPaul F WorleyAkira SawaHyung-Bae Kwon
Published in: Nature communications (2022)
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.
Keyphrases
  • gene expression
  • spinal cord
  • single cell
  • dna methylation
  • healthcare
  • mental health
  • cancer therapy
  • genome wide
  • brain injury
  • rna seq
  • single molecule