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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number111036
JournalCell reports
Issue number1
StatePublished - Jul 5 2022


  • CP: Neuroscience
  • brain mapping
  • intersectional strategy
  • multi-transmitter neurons
  • the lateral habenula

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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