Molecular and Physiological Diversity of Nicotinic Acetylcholine Receptors in the Midbrain Dopaminergic Nuclei
Open accessAbstract
Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and GABAergic (Gaba) projection neurons of the substantia nigra (SN) and ventral tegmental area (VTA) are characterized by single-cell RT-PCR and patch-clamp recordings in slices of rat and wild-type, beta2-/-, alpha4-/-, and alpha7-/- mice. The eight nAChR subunits expressed in these nuclei, alpha3-7 and beta2-4, contribute to four different types of nAChR-mediated currents. Most DA neurons in the SN and VTA express two nAChR subtypes. One is inhibited by dihydro-beta-erythroidine (2 microm), alpha-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not contain the alpha7 subunit; it possesses a putative alpha4alpha6alpha5(beta2)(2) composition. The other subtype is inhibited by dihydro-beta-erythroidine (2 microm) and has a putative alpha4alpha5(beta2)(2) composition. Gaba neurons in the VTA exhibit a third subtype with a putative (alpha4)(2)(beta2)(3) composition, whereas Gaba neurons in the SN have either the putative (alpha4)(2)(beta2)(3) oligomer or the putative alpha4alpha6alpha5(beta2)(2) oligomer. The fourth subtype, a putative (alpha7)(5) homomer, is encountered in less than half of DA and Gaba neurons, in the SN as well as in the VTA. Neurons in the DA nuclei thus exhibit a diversity of nAChRs that might differentially modulate reinforcement and motor behavior.
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DA neurons express heteromeric nAChRs containing α4, α5, α6, β2, and β3 subunits in various combinations, with predominant subtypes being α4/β2/α5 and α4/α6/β2/β3.
“DA neurons express heteromeric nAChRs containing the α4, α5, α6, β2, and β3 subunits in various combinations, with the predominant subtypes being α4/β2/α5 and α4/α6/ β2/β3.”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Klink et al. 2001
In “The DA subtypes” (page unavailable), the paper proposes an α4/α5/β2 receptor, supporting one named subtype. But it proposes α4/α6/α5/β2—not α4/α6/β2/β3—for the other, and explicitly suggests that β3 does not enter DA somatodendritic receptors. The paper also describes these compositions as putative, rather than established. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAcute activation of nAChRs by nicotine can stimulate the firing of DA neurons.
“As noted in Section 1, it is clear that acute activation of nAChRs by nicotine can stimulate the firing of DA neurons (Grenhoff et al., 1986; Klink et al., 2001; Picciotto et al., 1998; Svensson et al., 1990).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Klink et al., 2001
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- Authors
- Klink, R., d'Exaerde, A. D. K., Zoli, M., & Changeux, J.-P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-03-01
- Volume
- 21
- Issue
- 5
- Pages
- 1452-1463
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762941
- OpenAlex
- W1651595496
- Cited by
- 674
- References
- 2
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 15 · 2019: 19 · 2018: 16 · 2017: 10 · 2016: 22 · 2015: 25 · 2014: 34 · 2013: 30 · 2012: 28
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- PubMed
- Funders
- Association pour la Recherche sur le Cancer
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- nicotinic acetylcholine receptors, dopaminergic neurons, GABAergic neurons, substantia nigra, ventral tegmental area, alpha7 subunit, alpha4 subunit, beta2 subunit, dihydro-beta-erythroidine, alpha-conotoxin MII, methyllycaconitine, receptor diversity, reinforcement, motor behavior
- MeSH terms
- Animals, Dopamine, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Mice, Mutant Strains, Microinjections, Neurons, Receptors, Nicotinic, RNA, Messenger, Substantia Nigra, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, Ventral Tegmental Area, Patch-Clamp Techniques, Nicotinic Agonists, Nicotinic Antagonists, Reverse Transcriptase Polymerase Chain Reaction, Protein Subunits, Mice, Rats, alpha7 Nicotinic Acetylcholine Receptor, 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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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