Targeting cells with single vectors using multiple-feature Boolean logic.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fenno, LE; Mattis, J; Ramakrishnan, C; Hyun, M; Lee, SY; He, M; Tucciarone, J; Selimbeyoglu, A; Berndt, A; Grosenick, L; Zalocusky, KA; Bernstein, H; Swanson, H; Perry, C; Diester, I; Boyce, FM; Bass, CE; Neve, R; Huang, ZJ; Deisseroth, K

Published Date

  • July 2014

Published In

Volume / Issue

  • 11 / 7

Start / End Page

  • 763 - 772

PubMed ID

  • 24908100

Pubmed Central ID

  • PMC4085277

Electronic International Standard Serial Number (EISSN)

  • 1548-7105

Digital Object Identifier (DOI)

  • 10.1038/nmeth.2996

Language

  • eng

Conference Location

  • United States