TY - JOUR
T1 - Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex
AU - He, Miao
AU - Tucciarone, Jason
AU - Lee, Soo Hyun
AU - Nigro, Maximiliano José
AU - Kim, Yongsoo
AU - Levine, Jesse Maurica
AU - Kelly, Sean Michael
AU - Krugikov, Illya
AU - Wu, Priscilla
AU - Chen, Yang
AU - Gong, Lin
AU - Hou, Yongjie
AU - Osten, Pavel
AU - Rudy, Bernardo
AU - Huang, Z. Josh
N1 - Funding Information:
We are grateful to Hongkui Zeng for providing Ai3 and Ai65 vectors and the Ai65 mouse line, Dawen Cai, Jeff Lichtman, and Joshua Sanes for sharing the Brainbow vector and antibodies, Sang Yong Kim for help with generation of knockin mice, and Adam Kepecs, Hiroki Taniguchi, and Dhananjay Huilgol for comments on the manuscript. This work was supported in part by NIH 5U01 MH078844-05, CSHL Robertson Neuroscience Fund to Z.J.H., National Natural Science Foundation of China 31471037, 91432106, 31421091, and Shanghai Yangfan 14YF1400500 to M.H., NARSAD Young Investigator Grant to Y.K., NIH U01MH105971 to P.O., and NIH R01NS30989 and P01NS074972 to B.R., J.T, S.M.K., and J.M.L. are supported by NRSA F30 Medical Scientist Predoctoral Fellowships.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/21
Y1 - 2016/9/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2016.08.021
DO - 10.1016/j.neuron.2016.08.021
M3 - Article
C2 - 27618674
AN - SCOPUS:84991225168
SN - 0896-6273
VL - 91
SP - 1228
EP - 1243
JO - Neuron
JF - Neuron
IS - 6
ER -