Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors
Open accessAbstract
The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-β-erythroidine and mecamylamine and persisted in the presence of the α7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the α7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the α4, α5, and β2 nicotinic receptor subunits. Therefore, these results provide a role for non-α7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine.
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Cholinergic receptors are expressed by inhibitory and excitatory cortical neurons and on the terminals of thalamocortical neurons.
“Cholinergic receptors are expressed by inhibitory and excitatory cortical neurons119,124,158–164, as well as on the terminals of thalamocortical neurons165–169.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [163]
VIP+ interneurons are strongly depolarized by nicotine or ACh.
“In particular, VIP+ interneurons express nAChRs and are strongly depolarized by nicotine or ACh119,124,163.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [163]
VIP+ interneurons express nAChRs.
“In particular, VIP+ interneurons express nAChRs and are strongly depolarized by nicotine or ACh119,124,163.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [163]
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Disney, A. A., Aoki, C., & Hawken, M. J. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00188.2012 · Cited by 57 · see citing works
Staiger, J. F., Masanneck, C., Schleicher, A., & Zuschratter, W. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.10953 · Cited by 53 · see citing works
Askew, C., Intskirveli, I., & Metherate, R. (2017) · eneuro · doi:10.1523/eneuro.0192-17.2017 · Cited by 18 · see citing works
- Authors
- Porter, J. T., Cauli, B., Tsuzuki, K., Lambolez, B., Rossier, J., & Audinat, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-07-01
- Volume
- 19
- Issue
- 13
- Pages
- 5228-5235
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782331
- OpenAlex
- W2139250347
- Cited by
- 262
- References
- 64
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 11 · 2018: 17 · 2017: 13 · 2016: 11 · 2015: 16 · 2014: 13 · 2013: 13 · 2012: 17
- FWCI
- 3.56
- 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
- European Commission (960589)
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- nicotinic acetylcholine receptors, neocortical interneurons, vasoactive intestinal peptide, cholecystokinin, parvalbumin interneurons, somatostatin interneurons, acetylcholine
- MeSH terms
- Acetylcholine, Action Potentials, Animals, Calcium, Cholecystokinin, Interneurons, Receptors, Nicotinic, RNA, Messenger, Tetrodotoxin, Vasoactive Intestinal Peptide, Gene Expression, Rats, Wistar, Pyramidal Cells, Cholinergic Agents, Excitatory Amino Acid Antagonists, GABA Antagonists, Neocortex, Reverse Transcriptase Polymerase Chain Reaction, 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.
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