Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex

He, M., Tucciarone, J., Lee, S., Nigro, M. J., Kim, Y., Levine, J. M., Kelly, S. M., Krugikov, I., Wu, P., Chen, Y., Gong, L., Hou, Y., Osten, P., Rudy, B., Huang, Z. J. (September 2016) Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex. Neuron, 91 (6). pp. 1228-1243. ISSN 1097-4199 (Electronic)0896-6273 (Linking)

Abstract

Systematic genetic access to GABAergic cell types will facilitate studying the function and development of inhibitory circuitry. However, single gene-driven recombinase lines mark relatively broad and heterogeneous cell populations. Although intersectional approaches improve precision, it remains unclear whether they can capture cell types defined by multiple features. Here we demonstrate that combinatorial genetic and viral approaches target restricted GABAergic subpopulations and cell types characterized by distinct laminar location, morphology, axonal projection, and electrophysiological properties. Intersectional embryonic transcription factor drivers allow finer fate mapping of progenitor pools that give rise to distinct GABAergic populations, including laminar cohorts. Conversion of progenitor fate restriction signals to constitutive recombinase expression enables viral targeting of cell types based on their lineage and birth time. Properly designed intersection, subtraction, conversion, and multi-color reporters enhance the precision and versatility of drivers and viral vectors. These strategies and tools will facilitate studying GABAergic neurons throughout the mouse brain.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > GABAergic
organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex
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
Investigative techniques and equipment > Whole Brain Circuit Mapping
CSHL Authors:
Communities: CSHL labs > Huang lab
CSHL labs > Osten lab
Depositing User: Matt Covey
Date: 21 September 2016
Date Deposited: 22 Sep 2016 16:11
Last Modified: 08 Jul 2021 14:49
PMCID: PMC5223593
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33537

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