Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters
Abstract
Three closely related proteins transport glutamate into synaptic vesicles for release by exocytosis. Complementary patterns of expression in glutamatergic terminals have been reported for VGLUT1 and VGLUT2. VGLUT3 shows expression by many cells not considered to be glutamatergic. Here we describe the changes in VGLUT expression that occur during development. VGLUT1 expression increases gradually after birth and eventually predominates over the other isoforms in telencephalic regions. Expressed at high levels shortly after birth, VGLUT2 declines with age in multiple regions, in the cerebellum by 14-fold. In contrast, Coexpression of the two isoforms occurs transiently during development as well as permanently in a restricted subset of glutamatergic terminals in the adult. VGLUT3 is transiently expressed at high levels by select neuronal populations, including terminals in the cerebellar nuclei, scattered neurons in the cortex, and progenitor-like cells, implicating exocytotic glutamate release in morphogenesis and development. VGLUT3 also colocalizes extensively during development with the neuronal vesicular monoamine transporter VMAT2, with the vesicular acetylcholine transporter VAChT, and with the vesicular gamma-aminobutyric acid transporter VGAT. Such coexpression occurs particularly at some specific developmental stages and is restricted to certain sets of cells. In skeletal muscle, VGLUT3 localizes to granular organelles in the axon terminal as well as in the muscle sarcoplasm. The results suggest novel mechanisms and roles for regulated transmitter release.
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EM studies of dentate gyrus axon terminals found anatomical evidence for GABAergic and glutamatergic vesicular transporters in the same axon.
“Electron microscopy (EM) studies of axon terminals in the dentate gyrus (DG) have demonstrated anatomical evidence for the existence of GABAergic and glutamatergic vesicular transporters in the same axon.27”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [27]
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- Authors
- Boulland, J., Qureshi, T., Seal, R. P., Rafiki, A., Gundersen, V., Bergersen, L. H., Fremeau, R. T., Edwards, R. H., Storm‐Mathisen, J., & Chaudhry, F. A.
- Affiliations
- University of Oslo (NO)
- University of California, San Francisco (US)
- Corresponding author
- Chaudhry, Farrukh A.
- ORCID
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2004-10-28
- Volume
- 480
- Issue
- 3
- Pages
- 264-280
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2153213393
- Cited by
- 280
- References
- 88
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 18 · 2012: 15
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- vesicular glutamate transporter, VGLUT1, VGLUT2, VGLUT3, glutamate release, synaptic vesicles, neuronal development, telencephalon, cerebellum, cerebellar nuclei, vesicular monoamine transporter 2, vesicular acetylcholine transporter, vesicular GABA transporter, axon terminals, skeletal muscle, progenitor-like cells, morphogenesis, glutamatergic terminals
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Exocytosis, Mice, Inbred C57BL, Morphogenesis, Neurons, Stem Cells, Synaptic Vesicles, Tissue Distribution, Up-Regulation, Prosencephalon, Neurotransmitter Agents, Gene Expression Regulation, Developmental, Glutamic Acid, Protein Isoforms, Membrane Transport Proteins, Amino Acid Transport Systems, Acidic, Amino Acid Transport System X-AG, Vesicular Transport Proteins, Vesicular Glutamate Transport Proteins, Vesicular Glutamate Transport Protein 1, Vesicular Glutamate Transport Protein 2, Mice, Rats
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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