The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone
Abstract
Three subtypes of vesicular transporters accumulate glutamate into synaptic vesicles to promote its vesicular release. One of the subtypes, VGLUT3, is expressed in neurons, including cholinergic striatal interneurons, that are known to release other classical transmitters. Here we showed that disruption of the Slc17a8 gene (also known as Vglut3) caused an unexpected hypocholinergic striatal phenotype. Vglut3(-/-) mice were more responsive to cocaine and less prone to haloperidol-induced catalepsy than wild-type littermates, and acetylcholine release was decreased in striatum slices lacking VGLUT3. These phenotypes were associated with a colocalization of VGLUT3 and the vesicular acetylcholine transporter (VAChT) in striatal synaptic vesicles and the loss of a synergistic effect of glutamate on vesicular acetylcholine uptake. We propose that this vesicular synergy between two transmitters is the result of the unbalanced bioenergetics of VAChT, which requires anion co-entry for continuing vesicular filling. Our study reveals a previously unknown effect of glutamate on cholinergic synapses with potential functional and pharmacological implications.
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“These complementary dependencies may explain the observed synergies between vGluT and VAChT or vGluT and the vesicular zinc transporter (ZnT3) when these are localized to the same synaptic vesicle.5,21,22”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [22]
In the citing paper
“However, many of these neurons also contain the vesicular glutamate transporters (vGluT1/2/3) that are coexpressed with molecular machinery for Ach synthesis, vesicular packaging, and release in multiple brain regions, including the striatum, basal forebrain, and medial habenula (mHb).22,56,57”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [22]
In the citing paper
“Immunogold EM and immunoprecipitation experiments suggest that vGluT and VAChT co-package glutamate and ACh into the same synaptic vesicle in both mHb to IPN synapses and striatal cholinergic to medium spiny neuron synapses 21,22,56 (Figure 1A).”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [22]
In the citing paper
“Interestingly, several groups have found that vGluT and VAChT function synergistically and that depletion of one transporter or neurotransmitter also depletes loading and release of the other.21,22,63,69”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [22]
In the citing paper
“Several groups have found evidence for Ach and glutamate being copackaged into the same synaptic vesicles at this synapse 21,22,56,124”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [22]
Citations
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VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate
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A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons
Gras, C., Herzog, E., Bellenchi, G. C., Bernard, V., Ravassard, P., Pohl, M., Gasnier, B., Giros, B., & El Mestikawy, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05442.2002 · Cited by 639
Self-citationHerzog, É., Bellenchi, G. C., Gras, C., Bernard, V., Ravassard, P., Bedet, C., Gasnier, B., Bruno Giros, A., & Mestikawy, S. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-22-j0001.2001 · Cited by 625
Self-citationFremeau, R. T., Burman, J. L., Qureshi, T., Tran, C. H., Proctor, J. M., Johnson, J., Zhang, H., Sulzer, D. L., Copenhagen, D. R., Storm‐Mathisen, J., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222546799 · Cited by 568
Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein
Fleming, S. M., Salcedo, J. D., Fernagut, P., Rockenstein, E. M., Masliah, E., Levine, M. S., & Chesselet, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3080-04.2004 · Cited by 477
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Imaging of cAMP/PKA dynamics induced by catecholamines in the neocortical network
Nomura, S. (2014) · theses.fr (ABES) · doi:10.70675/362841cbzcc8bz415dzbd43zdfc38b35cdc1
Mansouri-Guilani, N. (2017) · theses.fr (ABES) · doi:10.70675/99ced3b5zeac6z4eb2z8e6cz01bcad7cf2d9
Régulation du sommeil et de l’anxiété par VGLUT3, le transporteur vésiculaire du glutamate de type 3
Henderson, F. J. (2019) · theses.fr (ABES) · doi:10.70675/72ea7d04ze3b3z4768zab1fz66b684e1ed22
Andrianarivelo, A. (2020) · theses.fr (ABES) · doi:10.70675/1eda447azd2ecz4675zbc7azd4baf9a480db
Ultrastructural and molecular analysis of cortico-striatal dopamine hub synapses
Lapios, P. (2024) · theses.fr (ABES) · doi:10.70675/527646a6zd9b5z4935z80ebz0950bba9d08e
The role of VGLUT3 in behaviour, with a focus on VGLUT3 positive neurons of the median raphe region
Fazekas, C. L. (2023) · theses.fr (ABES) · doi:10.70675/517bbedbz9f8ez4541z9f7dzead2ac6bb84e
Communication in the Depressed Brain
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Pujol, M., Bernard, V., Mestikawy, S. E., Fabre, V., & Daumas, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.09.750466
Self-citationBindingDB Entry 50039296: Rose Bengal analogs and vesicular glutamate transporters (VGLUTs).
BindingDB (2013) · UC San Diego · doi:10.7270/q29024s4
On the chloride dependence of vesicular glutamate transport
Schenck, S. (2010) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-362
Metadata
- Authors
- Gras, C., Amilhon, B., Lepicard, È. M., Poirel, O., Vinatier, J., Herbin, M., Dumas, S., Tzavara, E. T., Wade, M. R., Nomikos, G. G., Hanoun, N., Saurini, F., Kemel, M.-L., Gasnier, B., Giros, B., & Mestikawy, S. E.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Amgen (United States) (US)
- Corresponding author
- Mestikawy, Salah El
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2008-02-17
- Volume
- 11
- Issue
- 3
- Pages
- 292-300
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2068075585
- Cited by
- 211
- References
- 47
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 10 · 2019: 11 · 2018: 8 · 2017: 13 · 2016: 14 · 2015: 17 · 2014: 16 · 2013: 8 · 2012: 12
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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 › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- VGLUT3, vesicular glutamate transporter, striatum, acetylcholine release, vesicular acetylcholine transporter, cholinergic interneurons, cocaine sensitivity, haloperidol-induced catalepsy, synaptic vesicles, cholinergic synapses
- MeSH terms
- Acetylcholine, Animals, Corpus Striatum, Drug Resistance, Interneurons, Motor Activity, Synaptic Transmission, Organ Culture Techniques, Synaptic Vesicles, Antipsychotic Agents, Down-Regulation, Presynaptic Terminals, Mice, Knockout, Glutamic Acid, Dopamine Uptake Inhibitors, Amino Acid Transport Systems, Acidic, Vesicular Acetylcholine Transport Proteins, Mice, Rats
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