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Publication : A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion.

First Author  Kim CK Year  2020
Journal  Cell Volume  183
Issue  7 Pages  2003-2019.e16
PubMed ID  33308478 Mgi Jnum  J:378885
Mgi Id  MGI:6490167 Doi  10.1016/j.cell.2020.11.015
Citation  Kim CK, et al. (2020) A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion. Cell 183(7):2003-2019.e16
abstractText  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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