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Cited by 25Advanced Fluorescence Microscopy TechniquesBiotin and Related StudiesNeuroscience and Neuropharmacology Research

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Rapid, biochemical tagging of cellular activity history in vivo

Open access
Zhang, Run, Anguiano, Maribel, Aarrestad, Isak K., Lin, Sophia, Chandra, Joshua, Vadde, Sruti S., Olson, David E., Kim, Christina K.·2024·Nature Methods
DOI 10.1038/s41592-024-02375-7PMC PMC11399108

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Abstract

Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca 2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely behaving animals. Here we engineered an enzyme-catalyzed approach that rapidly and biochemically tags cells with elevated Ca 2+ in vivo. Ca 2+ -activated split-TurboID (CaST) labels activated cells within 10 min with an exogenously delivered biotin molecule. The enzymatic signal increases with Ca 2+ concentration and biotin labeling time, demonstrating that CaST is a time-gated integrator of total Ca 2+ activity. Furthermore, the CaST readout can be performed immediately after activity labeling, in contrast to transcriptional reporters that require hours to produce signal. These capabilities allowed us to apply CaST to tag prefrontal cortex neurons activated by psilocybin, and to correlate the CaST signal with psilocybin-induced head-twitch responses in untethered mice.

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Metadata

Authors
Zhang, R., Anguiano, M., Aarrestad, I. K., Lin, S., Chandra, J., Vadde, S. S., Olson, D. E., & Kim, C. K.
Affiliations
University of California, Davis (US)
Corresponding author
Kim, Christina K.
ORCID
Venue
Nature Methods
Publisher
Springer Science and Business Media LLC
Published
2024-08-05
Volume
21
Issue
9
Pages
1725-1735
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
DOI
10.1038/s41592-024-02375-7
PMC
PMC11399108
OpenAlex
W4401339284
Cited by
25
References
6
Citations by year
2026: 10 · 2025: 12 · 2024: 3
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Methods (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Brain and Behavior Research Foundation (NARSAD Young Investigator Grant #30238)
  • Kinship Foundation (Searle Scholars Program #SSP-2022-107)
  • Arnold and Mabel Beckman Foundation (Beckman Young Investigator Award)
  • U.S. Department of Health & Human Services | National Institutes of Health (DP2MH136588, T32 MH112507, R35GM148182)
  • National Science Foundation (NRT NeuralStorm #2152260, GRFP #000895154)
  • Boone Family Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
intracellular calcium, psilocybin, prefrontal cortex neurons, head-twitch response, neuronal activity imaging

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