Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex.
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.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Miao
M
He
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Program in Neuroscience and Medical Scientist Training Program, Stony Brook University, Stony Brook, NY 11790, USA.
Jason
J
Tucciarone
New York University Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA.
SooHyun
S
Lee
New York University Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA.
Maximiliano José
MJ
Nigro
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Yongsoo
Y
Kim
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Program in Neuroscience and Medical Scientist Training Program, Stony Brook University, Stony Brook, NY 11790, USA.
Jesse Maurica
JM
Levine
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Program in Neuroscience and Medical Scientist Training Program, Stony Brook University, Stony Brook, NY 11790, USA.
Sean Michael
SM
Kelly
New York University Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA.
Illya
I
Krugikov
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Priscilla
P
Wu
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Yang
Y
Chen
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Ling
L
Gong
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Yongjie
Y
Hou
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Pavel
P
Osten
New York University Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA.
Bernardo
B
Rudy
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: huangj@cshl.edu.
Z Josh
ZJ
Huang
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D059330:GABAergic Neurons / Q000166:cytology*; D005822:Genetic Vectors; D051379:Mice; D009154:Mutation; D058953:Neural Stem Cells / Q000166:cytology*; D045522:Recombinases / Q000235:genetics*; D014780:Viruses
D045522:Recombinases