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Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons

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Zhang, Shiliang, Qi, Jia, Li, Xueping, Wang, Hui-Ling, Britt, Jonathan P, Hoffman, Alexander F, Bonci, Antonello, Lupica, Carl R +1 more·2015·Nature Neuroscience

Abstract

Mesoaccumbens fibers are thought to co-release dopamine and glutamate. However, the mechanism is unclear, and co-release by mesoaccumbens fibers has not been documented. Using electron microcopy, we found that some mesoaccumbens fibers have vesicular transporters for dopamine (VMAT2) in axon segments that are continuous with axon terminals that lack VMAT2, but contain vesicular glutamate transporters type 2 (VGluT2). In vivo overexpression of VMAT2 did not change the segregation of the two vesicular types, suggesting the existence of highly regulated mechanisms for maintaining this segregation. The mesoaccumbens axon terminals containing VGluT2 vesicles make asymmetric synapses, commonly associated with excitatory signaling. Using optogenetics, we found that dopamine and glutamate were released from the same mesoaccumbens fibers. These findings reveal a complex type of signaling by mesoaccumbens fibers in which dopamine and glutamate can be released from the same axons, but are not normally released at the same site or from the same synaptic vesicles.

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  • vGluT2+ and vMAT2+ vesicles segregate into distinct vesicle populations and separate axonal boutons or microdomains.

    “Immunogold EM studies and immunoprecipitation experiments suggest that vGluT2+ and vMAT2+ vesicles segregate into distinct vesicle populations and even separate axonal boutons/microdomains, 111”

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Authors
Zhang, S., Qi, J., Li, X., Wang, H.-L., Britt, J. P., Hoffman, A. F., Bonci, A., Lupica, C. R., & Morales, M.
Affiliations
National Institutes of Health (US)
Corresponding author
Morales, Marisela
Venue
Nature Neuroscience
Published
2015-02-09
Volume
18
Issue
3
Pages
386-392
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2069677215
Cited by
252
References
38
Citations by year
2026: 9 · 2025: 20 · 2024: 20 · 2023: 25 · 2022: 15 · 2021: 24 · 2020: 21 · 2019: 22 · 2018: 24 · 2017: 25 · 2016: 31 · 2015: 16
FWCI
14.86
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (ZIADA000511)
  • National Institute of Neurological Disorders and Stroke (NS050274, P30NS050274)
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
dopamine, glutamate, CO release, vesicular monoamine transporter 2, VGLUT2, vesicular transporters, synaptic vesicles, asymmetric synapses, axon terminals, striatum
MeSH terms
Channelrhodopsins, Animals, Axons, Dopamine, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Nucleus Accumbens, Synaptic Vesicles, Transduction, Genetic, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, Ventral Tegmental Area, Glutamic Acid, Membrane Microdomains, Vesicular Glutamate Transport Protein 2, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques

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