Cited by 27Neuroscience and Neuropharmacology ResearchNeurobiology and Insect Physiology ResearchMemory and Neural Mechanisms

Intersectional mapping of multi-transmitter neurons and other cell types in the brain

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Xu, Jian, Jo, Andrew, DeVries, Raina P., Deniz, Sercan, Cherian, Suraj, Sunmola, Idris, Song, Xingqi, Marshall, John J. +6 more·2022·Cell Reports

Abstract

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.

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Crossref · 10.1016/j.celrep.2022.111036

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  • A screen found that 30 brain regions contain neurons expressing genes required for vesicular packaging of both GABA and glutamate.

    “a screen for GABA/glutamate coreleasing neurons revealed that 30 different brain regions have neurons that express the genes required for synaptic vesicle packaging of both GABA (vGAT; Slc32a1) and glutamate (vGluT2/3; Slc17a6/Slc17a8).8”
  • GABA/glutamate cotransmission may be more widespread than previously thought.

    “These findings indicated that GABA/glutamate cotransmission may be more widespread than previously thought.”

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Authors
Xu, J., Jo, A., DeVries, R. P., Deniz, S., Cherian, S., Sunmola, I., Song, X., Marshall, J. J., Gruner, K. A., Daigle, T. L., Contractor, A., Lerner, T. N., Zeng, H., & Zhu, Y.
Affiliations
  • Northwestern University (US)
  • University of Chicago (US)
  • Shanghai Jiao Tong University (CN)
  • Allen Institute for Brain Science (US)
Corresponding author
Zhu, Yongling
Venue
Cell Reports
Publisher
Elsevier BV
Published
2022-07
Volume
40
Issue
1
Pages
111036
ISSN
2211-1247 (ISSN-L)
OpenAlex
W4284706549
Cited by
27
References
67
Citations by year
2026: 5 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 4
FWCI
2.43
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (T32 EY025202, F31 EY031985, R01 EY030169, R01 EY018204, R01 MH099114)
  • Research to Prevent Blindness
  • Whitehall Foundation (2017-05-20, Y.Z. 2017-05-20)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
intersectional genetics, vesicular glutamate transporter, vesicular GABA transporter, glutamatergic neurons, GABAergic neurons, lateral habenula, neuronal cell types, mouse brain
MeSH terms
Animals, Mice, Transgenic, Neurons, Habenula, Vesicular Glutamate Transport Proteins, Mice

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