5-HT3Receptors Mediate Serotonergic Fast Synaptic Excitation of Neocortical Vasoactive Intestinal Peptide/Cholecystokinin Interneurons
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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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Vip interneurons are strongly depolarized by 5HT3aR agonists and show nicotinic acetylcholine responses, suggesting that activity in neuromodulatory centers such as the raphe and basal forebrain could rapidly activate these interneurons.
“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
The paper reports rapid 5-HT3 receptor-mediated excitation of neocortical VIP/CCK interneurons by serotonergic fibers from the raphe (Evoked synaptic responses; page not supplied). It also reports that cells responsive to the 5-HT3 agonist mCPBG responded to a nicotinic agonist (Coexpression of 5-HT3 Rs and nicotinic receptors; page not supplied). It does not establish the claim for all VIP or 5-HT3A-expressing interneurons, or specifically link their rapid activation to basal forebrain neurons. (LLM, conf=0.84)
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- 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
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.
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