Targeting cells with single vectors using multiple-feature Boolean logic

Fenno, L. E., Mattis, J., Ramakrishnan, C., Hyun, M., Lee, S. Y., He, M., Tucciarone, J., Selimbeyoglu, A., Berndt, A., Grosenick, L., Zalocusky, K. A., Bernstein, H., Swanson, H., Perry, C., Diester, I., Boyce, F. M., Bass, C. E., Neve, R., Huang, Z. J., Deisseroth, K. (2014) Targeting cells with single vectors using multiple-feature Boolean logic. Nature Methods, 11 (7). pp. 763-772. ISSN 15487091 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/24908100
DOI: 10.1038/nmeth.2996

Abstract

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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons

organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: Matt Covey
Date Deposited: 13 Jun 2014 15:27
Last Modified: 07 Apr 2015 15:42
PMCID: PMC4085277
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30307

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