期刊
CELL
卷 183, 期 7, 页码 2003-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.11.015
关键词
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资金
- Walter V. and Idun Berry Postdoctoral Fellowship Program
- EMBO longterm postdoctoral fellowship [ALTF 1022-2015]
- NIMH [R01 MH119353, F32 MH115668]
- Stanford Psychiatry
- Wu Tsai Neurosciences Institute
- NIDA [P50 DA042012]
- Defense Advanced Research Projects Agency Neuro-FAST program
- NOMIS Foundation
- Wiegers Family Fund
- Nancy and James Grosfeld Foundation
- H.L. Snyder Medical Foundation
- Samuel and Betsy Reeves Fund
- Gatsby Foundation
- AE Foundation
- Fresenius Foundation
- Chan Zuckerberg Biohub
The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here, we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE's modular design, we expressed an optogenetic channel selectively in this cell type and showed that direct recruitment of this otherwise genetically inaccessible population elicits behavioral aversion. The specificity and minute resolution of FLiCRE enables molecularly informed characterization, manipulation, and reprogramming of activated cellular ensembles.
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