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VGLUT3 (Vesicular Glutamate Transporter Type 3) Contribution to the Regulation of Serotonergic Transmission and Anxiety
Open accessAbstract
Three different subtypes of H(+)-dependent carriers (named VGLUT1-3) concentrate glutamate into synaptic vesicles before its exocytotic release. Neurons using other neurotransmitter than glutamate (such as cholinergic striatal interneurons and 5-HT neurons) express VGLUT3. It was recently reported that VGLUT3 increases acetylcholine vesicular filling, thereby, stimulating cholinergic transmission. This new regulatory mechanism is herein designated as vesicular-filling synergy (or vesicular synergy). In the present report, we found that deletion of VGLUT3 increased several anxiety-related behaviors in adult and in newborn mice as early as 8 d after birth. This precocious involvement of a vesicular glutamate transporter in anxiety led us to examine the underlying functional implications of VGLUT3 in 5-HT neurons. On one hand, VGLUT3 deletion caused a significant decrease of 5-HT(1A)-mediated neurotransmission in raphe nuclei. On the other hand, VGLUT3 positively modulated 5-HT transmission of a specific subset of 5-HT terminals from the hippocampus and the cerebral cortex. VGLUT3- and VMAT2-positive serotonergic fibers show little or no 5-HT reuptake transporter. These results unravel the existence of a novel subset of 5-HT terminals in limbic areas that might play a crucial role in anxiety-like behaviors. In summary, VGLUT3 accelerates 5-HT transmission at the level of specific 5-HT terminals and can exert an inhibitory control at the raphe level. Furthermore, our results suggest that the loss of VGLUT3 expression leads to anxiety-associated behaviors and should be considered as a potential new target for the treatment of this disorder.
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“In addition, deletion of either serotonin synthetic enzyme tryptophan hydroxylase 1 (Tph1) or vGluT3 (Slc18a8) from 5-HT/vGluT3+ neurons results in increased anxiety-like behaviors, suggesting that disrupting signaling from either transmitter has similar consequences.78,80”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [80]
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“In support of co-packaging, synergism has been reported between vGluT3 and vMAT2, by which vGluT3 promotes vesicular loading of 5-HT via vMAT2.80”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [80]
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Metadata
- Authors
- Amilhon, B., Lepicard, È., Renoir, T., Mongeau, R., Popa, D., Poirel, O., Miot, S., Gras, C., Gardier, A. M., Gallego, J., Hamon, M., Lanfumey, L., Gasnier, B., Giros, B., & El Mestikawy, S.
- Affiliations
- Inserm (FR)
- Université Paris-Sud (FR)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-02-10
- Volume
- 30
- Issue
- 6
- Pages
- 2198-2210
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6634029
- OpenAlex
- W2003949705
- Semantic Scholar
- 08049155b2834c64c0e593d14600785f1f240a6b
- Cited by
- 186
- References
- 55
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 10 · 2023: 6 · 2022: 7 · 2021: 14 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 14 · 2016: 16 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 15
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- VGLUT3, vesicular glutamate transporter, serotonergic neurotransmission, anxiety, 5-HT1A receptor, raphe nuclei, hippocampus, cerebral cortex, vesicular monoamine transporter 2, serotonin uptake, anxiety-like behavior, knockout mice
- MeSH terms
- Animals, Anxiety, Cerebral Cortex, Hippocampus, Synaptic Transmission, Raphe Nuclei, Serotonin, Autoreceptors, Presynaptic Terminals, Mice, Knockout, Amino Acid Transport Systems, Acidic, Receptor, Serotonin, 5-HT1A, Serotonin Plasma Membrane Transport Proteins, Vesicular Monoamine Transport Proteins, Mice
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