Cited by 186Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorCellular transport and secretion

VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety

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Amilhon, Bénédicte, Lepicard, Ève, Renoir, Thibault, Mongeau, Raymond, Popa, Daniela, Poirel, Odile, Miot, Stéphanie, Gras, Christelle +7 more·2010·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.5196-09.2010

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  • Deletion of either Tph1 or vGluT3 from 5-HT/vGluT3+ neurons increases anxiety-like behaviors, suggesting that disrupting signaling from either transmitter has similar consequences.

    “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”
  • Synergism has been reported between vGluT3 and vMAT2, by which vGluT3 promotes vesicular loading of 5-HT via vMAT2.

    “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”

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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)
Venue
The Journal of Neuroscience
Published
2010-02-10
Volume
30
Issue
6
Pages
2198-2210
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2003949705
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
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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