期刊
NATURE METHODS
卷 11, 期 7, 页码 763-U116出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.2996
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资金
- US National Institutes of Health [NINDS P30 NS069375-01A1]
- Stanford Medical Scientist Training Program (MSTP)
- Stanford Bio-X Fellowship
- Samsung Scholarship
- Robertson Neuroscience Fund of Cold Spring Harbor Laboratory
- Stony Brook University MSTP
- Howard Hughes Medical Institute International Student Fellowship
- National Science Foundation (NSF) [0801700]
- NSF Graduate Research Fellowship Program
- New York University MSTP
- Human Frontiers Science Project and German Academic Exchange Service (DAAD)
- US National Institute on Drug Abuse (NIDA) [DA024763]
- Wiegers Family Fund
- US National Institute of Mental Health
- NIDA
- Defense Advanced Research Projects Agency REPAIR Program
- Keck Foundation
- McKnight Foundation
- Gatsby Charitable Foundation
- Snyder Foundation
- Woo Foundation
- Tarlton Foundation
- Albert Yu and Mary Bechman Foundation
- Division Of Graduate Education
- Direct For Education and Human Resources [0801700] Funding Source: National Science Foundation
Precisely defining the roles of specific cell types is an intriguing frontier in the study of intact biological systems and has stimulated the rapid development of genetically encoded tools for observation and control. However, targeting these tools with adequate specificity remains challenging: most cell types are best defined by the intersection of two or more features such as active promoter elements, location and connectivity. Here we have combined engineered introns with specific recombinases to achieve expression of genetically encoded tools that is conditional upon multiple cell-type features, using Boolean logical operations all governed by a single versatile vector. We used this approach to target intersectionally specified populations of inhibitory interneurons in mammalian hippocampus and neurons of the ventral tegmental area defined by both genetic and wiring properties. This flexible and modular approach may expand the application of genetically encoded interventional and observational tools for intact-systems biology.
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