Three types of neurochemical projection from the bed nucleus of the stria terminalis to the ventral tegmental area in adult mice
Open accessAbstract
Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) play crucial roles in motivational control of behaviors, and their activity is regulated directly or indirectly via GABAergic neurons by extrinsic afferents from various sources, including the bed nucleus of the stria terminalis (BST). Here, the neurochemical composition of VTA-projecting BST neurons and their outputs to the VTA were studied in adult mouse brains. By combining retrograde tracing with fluorescence in situ hybridization for 67 kDa glutamate decarboxylase (GAD67) and vesicular glutamate transporters (VGluTs), VTA-targeting BST neurons were classified into GAD67-positive (GAD67(+))/VGluT3-negative (VGluT3(-)), GAD67(+)/VGluT3(+), and VGluT2(+) neurons, of which GAD67(+)/VGluT3(-) neurons constituted the majority (∼90%) of VTA-projecting BST neurons. GABAergic efferents from the BST formed symmetrical synapses on VTA neurons, which were mostly GABAergic neurons, and expressed GABA(A) receptor α1 subunit on their synaptic and extrasynaptic membranes. In the VTA, VGluT3 was detected in terminals expressing vesicular inhibitory amino acid transporter (VIAAT), plasmalemmal serotonin transporter, or neither. Of these, VIAAT(+)/VGluT3(+) terminals, which should include those from GAD67(+)/VGluT3(+) BST neurons, formed symmetrical synapses. When single axons from VGluT3(+) BST neurons were examined, almost all terminals were labeled for VIAAT, whereas VGluT3 was often absent from terminals with high VIAAT loads. VGluT2(+) terminals in the VTA exclusively formed asymmetrical synapses, which expressed AMPA receptors on postsynaptic membrane. Therefore, the major mode of the BST-VTA projection is GABAergic, and its activation is predicted to disinhibit VTA DAergic neurons. VGluT2(+) and VGluT3(+) BST neurons further supply additional projections, which may principally convey excitatory or inhibitory inputs, respectively, to the VTA.
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85.9% of cells were inhibitory and 14% excitatory, matching previous estimates.
“In agreement with previous estimates (Kudo et al., 2012), 85.9 % of the cells were inhibitory (expressing Gad1 and Gad2), while the remaining 14% were excitatory (expressing Slc17a6 (9.4%) or Slc17a8 (4.7%) (Figure S3C).”
From Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity (2019) · cites this paper as Kudo et al., 2012
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- Authors
- Kudo, T., Uchigashima, M., Miyazaki, T., Konno, K., Yamasaki, M., Yanagawa, Y., Minami, M., & Watanabe, M.
- Affiliations
- Hokkaido University (JP)
- Gunma University (JP)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-12-12
- Volume
- 32
- Issue
- 50
- Pages
- 18035-18046
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6621739
- OpenAlex
- W2042824787
- Cited by
- 177
- References
- 60
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 15 · 2020: 11 · 2019: 12 · 2018: 17 · 2017: 12 · 2016: 27 · 2015: 17 · 2014: 12 · 2013: 19
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (24790187, 24220007, 23300130)
- 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 › Neurological disorders and treatments
- Keywords
- bed nucleus of the stria terminalis, ventral tegmental area, GABAergic neurons, dopaminergic neurons, glutamatergic neurons, vesicular glutamate transporter, GAD67, synaptic asymmetry, GABA-A receptor alpha1 subunit, AMPA receptors, disinhibition
- MeSH terms
- Animals, Fluorescent Antibody Technique, Glutamate Decarboxylase, Immunohistochemistry, Male, Mice, Inbred C57BL, Neural Pathways, Neurons, Septal Nuclei, In Situ Hybridization, Fluorescence, Ventral Tegmental Area, Microscopy, Confocal, Vesicular Glutamate Transport Protein 2, Mice, Gene Knock-In Techniques, GABAergic Neurons
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