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

Miao He, Jason Tucciarone, Soo Hyun Lee, Maximiliano José Nigro, Yongsoo Kim, Jesse Maurica Levine, Sean Michael Kelly, Illya Krugikov, Priscilla Wu, Yang Chen, Lin Gong, Yongjie Hou, Pavel Osten, Bernardo Rudy, Z. Josh Huang

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1228-1243
Number of pages16
JournalNeuron
Volume91
Issue number6
DOIs
StatePublished - Sep 21 2016

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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