Intersectional mapping of multi-transmitter neurons and other cell types in the brain
Jian Xu,
Andrew Jo,
Raina P. DeVries,
Sercan Deniz,
Suraj Cherian,
Idris Sunmola,
Xingqi Song,
John J. Marshall,
Katherine A. Gruner,
Tanya L. Daigle,
Anis Contractor,
Talia N. Lerner,
Hongkui Zeng,
Yongling Zhu
Affiliations
Jian Xu
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Andrew Jo
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Raina P. DeVries
Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, IL 60637, USA
Sercan Deniz
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Suraj Cherian
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Idris Sunmola
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Xingqi Song
School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
John J. Marshall
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Katherine A. Gruner
Mouse Histology and Phenotyping Laboratory, Northwestern University, Chicago, IL 60611, USA
Tanya L. Daigle
Allen Institute for Brain Science, Seattle, WA 98109, USA
Anis Contractor
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Talia N. Lerner
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Hongkui Zeng
Allen Institute for Brain Science, Seattle, WA 98109, USA
Yongling Zhu
Departments of Ophthalmology and Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Corresponding author
Summary: Recent developments in intersectional strategies have greatly advanced our ability to precisely target brain cell types based on unique co-expression patterns. To accelerate the application of intersectional genetics, we perform a brain-wide characterization of 13 Flp and tTA mouse driver lines and selected seven for further analysis based on expression of vesicular neurotransmitter transporters. Using selective Cre driver lines, we created more than 10 Cre/tTA combinational lines for cell type targeting and circuit analysis. We then used VGLUT-Cre/VGAT-Flp combinational lines to identify and map 30 brain regions containing neurons that co-express vesicular glutamate and gamma-aminobutyric acid (GABA) transporters, followed by tracing their projections with intersectional viral vectors. Focusing on the lateral habenula (LHb) as a target, we identified glutamatergic, GABAergic, or co-glutamatergic/GABAergic innervations from ∼40 brain regions. These data provide an important resource for the future application of intersectional strategies and expand our understanding of the neuronal subtypes in the brain.
