Intersectional mapping of multi-transmitter neurons and other cell types in the brain
Open accessAbstract
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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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”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [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.”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [8]
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Fluorescent transgenic mouse models for whole-brain imaging in health and disease
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Chai, A. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1552145 · Cited by 8 · see citing works
Protocol to map multi-transmitter neurons in the mouse brain using intersectional strategy
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Prevalent co-release of glutamate and GABA throughout the mouse brainPreprint
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Synaptic sign switching mediates online dopamine updatesPreprint
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Colocalization of Neurotransmitters in Hippocampus and Afferent Systems: Possible Functional Role
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GABA-glutamate corelease is a mechanism for state-dependent neurotransmissionPreprint
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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
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 40
- Issue
- 1
- Pages
- 111036
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC9290751
- 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
- gold
- doi.org
- Licence
- 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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