Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate
Open accessAbstract
Coincident signaling by dopamine and glutamate is thought to be crucial for a variety of motivated behaviors. Previous work has suggested that some midbrain dopamine neurons are themselves capable of glutamate corelease, but this phenomenon remains poorly understood. Here, we expressed the light-activated cation channel Channelrhodopsin-2 (ChR2) in genetically defined midbrain dopamine neurons to stimulate exocytosis specifically from dopaminergic terminals in both the nucleus accumbens (NAc) shell and dorsal striatum of brain slices from adult mice. Optical activation resulted in robust glutamate-mediated EPSCs in all medium spiny neurons examined in the NAc shell. In contrast, optically evoked glutamatergic currents were nearly undetectable in the dorsal striatum. Further, we used a conditional knock-out mouse lacking vesicular glutamate transporter 2 (VGLUT2) specifically in dopamine neurons to determine whether VGLUT2 is required for the exocytotic release of glutamate from dopamine neurons. Our data show that conditional knock-out completely abolished all optically evoked glutamate release. These results provide definitive physiological evidence for VGLUT2-mediated glutamate release by mature dopamine neurons projecting to the NAc shell, but not to the dorsal striatum. Thus, the unique ability of NAc-projecting dopamine neurons to synchronously activate both dopamine and glutamate receptors may have crucial implications for the ability to respond to motivationally significant stimuli.
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Dopamine neurons projecting to ventral and dorsal striatum that express vGluT2 release glutamate onto striatal SPNs and CINs.
“dopamine neurons in the ventral midbrain projecting to ventral and dorsal striatum expressing the vGluT2 were confirmed, using optogenetic stimulation in brain slices, to release glutamate onto striatal SPNs and CINs.[108][109][110]”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [108]
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- Authors
- Stuber, G. D., Hnasko, T. S., Britt, J. P., Edwards, R. H., & Bonci, A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-06-16
- Volume
- 30
- Issue
- 24
- Pages
- 8229-8233
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2918390
- OpenAlex
- W2110665798
- Cited by
- 529
- References
- 26
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 28 · 2023: 21 · 2022: 19 · 2021: 30 · 2020: 30 · 2019: 32 · 2018: 35 · 2017: 38 · 2016: 40 · 2015: 51 · 2014: 50 · 2013: 33 · 2012: 33
- FWCI
- 15.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- A.P. Giannini Foundation
- Giannini Foundation of Agricultural Economics
- National Alliance for Research on Schizophrenia and Depression
- University of California, San Francisco
- National Institute on Drug Abuse (K01DA026504)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- dopaminergic neurons, nucleus accumbens shell, dorsal striatum, vesicular glutamate transporter 2, VGLUT2, medium spiny neurons, exocytosis, channelrhodopsin-2, optogenetic stimulation, glutamatergic neurotransmission, midbrain dopaminergic neurons, motivation
- MeSH terms
- Channelrhodopsins, Analysis of Variance, Animals, Benzazepines, Biophysics, Corpus Striatum, Dopamine, Electric Stimulation, Exocytosis, Female, Gene Expression Regulation, Male, Nucleus Accumbens, Photic Stimulation, Quinoxalines, Tyrosine 3-Monooxygenase, Presynaptic Terminals, Mice, Knockout, Patch-Clamp Techniques, Dopamine Antagonists, Excitatory Amino Acid Antagonists, Glutamic Acid, Excitatory Postsynaptic Potentials, Vesicular Glutamate Transport Protein 2, Mice, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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