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5-HT3Receptors Mediate Serotonergic Fast Synaptic Excitation of Neocortical Vasoactive Intestinal Peptide/Cholecystokinin Interneurons
Open accessAbstract
Neocortical neurons expressing the serotonin 5-HT3 receptor (5-HT3R) were characterized in rat acute slices by using patch-clamp recordings combined with single-cell RT-PCR and histochemical labeling. The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). The 5-HT3B subunit was never detected, indicating that 5-HT3Rs expressed by neocortical interneurons did not contain this subunit. In 5-HT3A-expressing VIP/CCK interneurons, serotonin induced fast membrane potential depolarizations by activating an inward current that was blocked by the selective 5-HT3R antagonist tropisetron. Furthermore, we observed close appositions between serotonergic fibers and the dendrites and somata of 5-HT3R-expressing neurons, suggestive of possible synaptic contacts. Indeed, in interneurons exhibiting rapid excitation by serotonin, local electrical stimulations evoked fast EPSCs of large amplitude that were blocked by tropisetron. Finally, 5-HT3R-expressing neurons were also excited by a nicotinic agonist, indicating that serotonergic and cholinergic fast synaptic transmission could converge onto VIP/CCK interneurons. Our results establish a clear correlation between the presence of the 5-HT3A receptor subunit in neocortical VIP/CCK GABAergic interneurons, its functional expression, and its synaptic activation by serotonergic afferent fibers from the brainstem raphe nuclei.
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“Like all 5HT3aR INs, Vip INs are strongly depolarized by 5HT3aR agonists (Ferezou et al., 2002; Lee et al., 2010), in addition to showing nicotinic ACh responses, suggesting that activity in neuromodulatory centers, such as raphe and basal forebrain neurons, could rapidly activate these interneurons.”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Ferezou et al., 2002
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Rostami, S., Alvar, A. A., Ghaderi, P., Dargahi, L., & Safari, M.-S. (2021) · Basic and Clinical Neuroscience Journal · doi:10.32598/bcn.2021.3180.1 · Cited by 2
Hu, W. (2011) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3164 · Cited by 1
The Diversity of Cortical Interneurons
Nakajima, M. (2025) · Digital Commons - RU (Rockefeller University) · doi:10.48496/pz2y-7v84 · Cited by 1
Gray, J. A., & Roth, B. L. (2007) · Wiley eBooks · doi:10.1002/9780470101001.hcn008 · Cited by 2
Hoyer, D. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.63723-7
Gil, J. L. (2009) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
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Metadata
- Authors
- Férézou, I., Cauli, B., Hill, E. L., Rossier, J., Hamel, E., & Lambolez, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-09-01
- Volume
- 22
- Issue
- 17
- Pages
- 7389-7397
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757992
- OpenAlex
- W2137514318
- Cited by
- 215
- References
- 70
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 10 · 2014: 14 · 2013: 9 · 2012: 11
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Commission
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- 5-HT3 receptor, serotonin, vasoactive intestinal peptide, cholecystokinin, GABAergic interneurons, neocortex, excitatory postsynaptic currents, tropisetron, nicotinic acetylcholine receptors, raphe nuclei, serotonergic afferents
- MeSH terms
- Animals, Cholecystokinin, gamma-Aminobutyric Acid, Interneurons, Membrane Potentials, Synaptic Transmission, Neurons, Afferent, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Vasoactive Intestinal Peptide, Rats, Wistar, Patch-Clamp Techniques, Nicotinic Agonists, Neocortex, Excitatory Postsynaptic Potentials, Reverse Transcriptase Polymerase Chain Reaction, Protein Subunits, Receptors, Serotonin, 5-HT3, Rats, In Vitro Techniques
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