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Mesocorticolimbic Glutamatergic Pathway
Open accessAbstract
The mesocorticolimbic dopamine (DA) system plays important roles in reward, motivation, learning, memory, and movement. This system arises from the A10 region, comprising the ventral tegmental area and three adjacent midline nuclei (caudal linear nucleus, interfascicular nucleus, and rostral linear nucleus of the raphe). DAergic and GABAergic neurons are intermingled in this region with recently discovered glutamatergic neurons expressing the vesicular glutamate transporter 2 (VGluT2). Here, we show by in situ hybridization and immunohistochemistry that there are two subpopulations of neurons expressing VGluT2 mRNA in the A10 region: (1) a major subpopulation that expresses VGluT2 but lacks tyrosine hydroxylase (TH; VGluT2-only neurons), present in each nucleus of the A10 region, and (2) a smaller subpopulation that coexpresses VGluT2 and TH (VGluT2-TH neurons). By quantitative real-time PCR, we determined the mRNA copy numbers encoding VGluT2 or TH in samples of individual microdissected TH immunoreactive (IR) neurons. Data from both in situ hybridization and from mRNA quantification showed that VGluT2 mRNA is not present in every TH-IR neuron, but restricted to a subset of TH-IR neurons located in the medial portion of the A10 region. By integration of tract tracing, in situ hybridization, and immunohistochemistry, we found that VGluT2-only neurons and VGluT2-TH neurons each innervate both the prefrontal cortex and the nucleus accumbens. These findings establish that in addition to the well-recognized mesocorticolimbic DA-only and GABA-only pathways, there exist parallel mesocorticolimbic glutamate-only and glutamate-DA pathways.
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“Of note here is that some of these dopaminergic neurons projecting to the various PFC subdomains are capable of co-releasing glutamate as well and have an exclusive excitatory effect on the GABAergic interneurons in the various layers of the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [170]
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“There are various sources of glutamatergic input projections including a subset of (non-)dopaminergic VTA neurons to GABAergic interneurons in the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [170]
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Metadata
- Authors
- Yamaguchi, T., Wang, H.-L., Li, X., Ng, T. H., & Morales, M.
- Affiliations
- National Institute on Drug Abuse (US)
- Corresponding author
- Morales, M.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-06-08
- Volume
- 31
- Issue
- 23
- Pages
- 8476-8490
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623324
- OpenAlex
- W2010408327
- Cited by
- 332
- References
- 38
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 32 · 2023: 23 · 2022: 19 · 2021: 16 · 2020: 24 · 2019: 18 · 2018: 19 · 2017: 20 · 2016: 22 · 2015: 33 · 2014: 26 · 2013: 22 · 2012: 18
- FWCI
- 10.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- ventral tegmental area, vesicular glutamate transporter 2, tyrosine hydroxylase, dopaminergic neurons, prefrontal cortex, nucleus accumbens, GABAergic neurons, neuronal subpopulations
- MeSH terms
- Animals, Dopamine, Immunohistochemistry, Neurons, Nucleus Accumbens, Raphe Nuclei, RNA, Messenger, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, In Situ Hybridization, Ventral Tegmental Area, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Vesicular Glutamate Transport Protein 2, Rats, Neuronal Tract-Tracers
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