CoChat
Sign Up
PreprintCited by 25Advanced Fluorescence Microscopy TechniquesBiotin and Related StudiesNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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.·2023·Nature Methods
DOI 10.1101/2023.09.06.556431PMC PMC11399108

Preprint — published as 10.1038/s41592-024-02375-7 · Paper page

Open this paper in CoChat — free accountOpen PDF

Abstract

Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across all 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 minutes 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 read-out 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.09.06.556431

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 62

  1. 10.1016/S0021-9258(19)83641-4 · DOI
  2. 2009, Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators, Nature methods, 6, 875, 10.1038/nmeth.1398 · DOI · Paper page
  3. 10.1038/nature12354 · DOI · Paper page
  4. 2015, Rational design of a high-affinity, fast, red calcium indicator R-CaMP2, Nature methods, 12, 64, 10.1038/nmeth.3185 · DOI
  5. 10.1038/nbt.3909 · DOI
  6. 10.1016/j.cell.2020.11.015 · DOI
  7. 10.1038/nbt.3902 · DOI
  8. 10.1126/science.1260922 · DOI
  9. 2014, An optogenetic gene expression system with rapid activation and deactivation kinetics, Nature chemical biology, 10, 196, 10.1038/nchembio.1430 · DOI
  10. 2009, A bright and photostable photoconvertible fluorescent protein, Nature Methods, 6, 131, 10.1038/nmeth.1296 · DOI
  11. 10.1126/science.aan6747 · DOI · Paper page
  12. 10.1126/science.1143839 · DOI
  13. 10.1038/nature11028 · DOI
  14. 10.1016/j.neures.2019.12.020 · DOI
  15. 10.1016/j.cell.2015.06.027 · DOI
  16. 10.1073/pnas.1919528117 · DOI
  17. 10.1083/jcb.201112098 · DOI · Paper page
  18. 10.1038/nbt.4201 · DOI · Paper page
  19. 10.1111/j.1471-4159.1987.tb04107.x · DOI
  20. 2020, Imaging biotin trafficking in vivo with positron emission tomography, Journal of medicinal chemistry, 63, 8265, 10.1021/acs.jmedchem.0c00494 · DOI
  21. 10.1371/journal.pone.0018556 · DOI
  22. 10.1016/S0168-9525(00)89040-X · DOI
  23. 10.1038/gt.2011.11 · DOI
  24. 10.7554/eLife.43826 · DOI
  25. 2016, Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain, Nature methods, 13, 325, 10.1038/nmeth.3770 · DOI
  26. 10.1016/S0278-5846(96)00157-1 · DOI · Paper page
  27. 2019, Genetic labeling reveals temporal and spatial expression pattern of D2 dopamine receptor in rat forebrain, Brain Structure and Function, 224, 1035, 10.1007/s00429-018-01824-2 · DOI
  28. 10.1016/j.brainresbull.2011.11.006 · DOI
  29. 10.1016/j.phrs.2016.05.010 · DOI
  30. 2015, Structure and function of serotonin G protein-coupled receptors, Pharmacology & therapeutics, 150, 129, 10.1016/j.pharmthera.2015.01.009 · DOI
  31. 2004, Dopamine receptor signaling, Journal of receptors and signal transduction, 24, 165, 10.1081/RRS-200029981 · DOI
  32. 10.1016/j.cellsig.2020.109717 · DOI
  33. 2018, Psychedelics promote structural and functional neural plasticity, Cell reports, 23, 3170, 10.1016/j.celrep.2018.05.022 · DOI · Paper page
  34. 10.1126/science.adf0435 · DOI
  35. 2021, Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo, Neuron, 109, 2535, 10.1016/j.neuron.2021.06.008 · DOI · Paper page
  36. Cameron, L.P. et al. 5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines. ACS Chemical Neuroscience (2023). · DOI
  37. 10.1007/s00221-013-3579-0 · DOI · Paper page
  38. 2020, Psychedelics, but not ketamine, produce persistent antidepressant-like effects in a rodent experimental system for the study of depression, ACS chemical neuroscience, 11, 864, 10.1021/acschemneuro.9b00493 · DOI · Paper page
  39. 10.1073/pnas.2022489118 · DOI · Paper page
  40. 10.1038/s41586-020-3008-z · DOI · Paper page
  41. 1963, A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine, British journal of pharmacology and chemotherapy, 20, 106, 10.1111/j.1476-5381.1963.tb01302.x · DOI
  42. 10.1007/s00213-013-3006-z · DOI
  43. 10.1016/j.neuron.2007.01.008 · DOI · Paper page
  44. 10.1177/0269881120959614 · DOI · Paper page
  45. 2023, Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin, ACS Chemical Neuroscience, 14, 468, 10.1021/acschemneuro.2c00637 · DOI
  46. 10.1523/JNEUROSCI.6377-11.2012 · DOI
  47. 2019, A hallucinogenic serotonin-2A receptor agonist reduces visual response gain and alters temporal dynamics in mouse V1, Cell reports, 26, 3475, 10.1016/j.celrep.2019.02.104 · DOI
  48. 10.1038/nn.3329 · DOI · Paper page
  49. 10.1016/j.cell.2021.03.043 · DOI · Paper page
  50. 2022, Cell type-specific biotin labeling in vivo resolves regional neuronal and astrocyte proteomic differences in mouse brain, Nature Communications, 13, 2927, 10.1038/s41467-022-30623-x · DOI
  51. 10.1038/nn.4593 · DOI · Paper page
  52. 10.1126/science.aaa6090 · DOI · Paper page
  53. Wang, X. et al. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science , eaa t5691 (2018). · DOI · Paper page
  54. 2023, MALDI HiPLEX-IHC: multiomic and multimodal imaging of targeted intact proteins in tissues, Frontiers in Chemistry, 11, 1182404, 10.3389/fchem.2023.1182404 · DOI
  55. 2017, Simultaneous epitope and transcriptome measurement in single cells, Nature methods, 14, 865, 10.1038/nmeth.4380 · DOI · Paper page
  56. 2022, ColabFold: making protein folding accessible to all, Nature methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  57. 10.1016/j.neuron.2007.11.030 · DOI
  58. 10.1099/0022-1317-73-3-653 · DOI
  59. 10.1038/nature12466 · DOI · Paper page
  60. 2013, CellSegm-a MATLAB toolbox for high-throughput 3D cell segmentation, Source code for biology and medicine, 8, 16, 10.1186/1751-0473-8-16 · DOI
  61. 2021, Cellpose: a generalist algorithm for cellular segmentation, Nature methods, 18, 100, 10.1038/s41592-020-01018-x · DOI · Paper page
  62. Pachitariu, M. et al. Suite2p: beyond 10,000 neurons with standard two-photon microscopy. BioRxiv, 061507 (2016). · DOI

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
openRxiv
Published
2023-09-08
Volume
21
Issue
9
Pages
1725-1735
ISSN
1548-7091 (ISSN-L)
DOI
10.1101/2023.09.06.556431
PMC
PMC11399108
OpenAlex
W4401339284
Cited by
25
References
1
Citations by year
2026: 10 · 2025: 12 · 2024: 3
FWCI
4.82
Type
journal article
Language
en
Open access
Licence
cc-by
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
  • National Science Foundation (GRFP #000895154, 1019469, 2152260)
  • U.S. Department of Health and Human Services (T32MH112507, R35GM148182, DP2MH136588)
  • Brain and Behavior Research Foundation
  • Arnold and Mabel Beckman Foundation
  • Kinship Foundation (Searle Scholars Program #SSP-2022-107)
  • National Alliance for Research on Schizophrenia and Depression
  • Searle Scholars Program
  • National Institutes of Health
  • University of California, Davis (T32 MH112507)
  • National Institute of Mental Health (DP2MH136588, T32MH082174, T32MH112507)
  • National Institute of General Medical Sciences (R01GM128997, R25GM116690, R35GM148182)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review