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PMID: 11222635 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 5 ·2001-03-01 ·Pages 1452-63

Klink R, de Kerchove d'Exaerde A, Zoli M, Changeux JP

Abstract

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.

MeSH Terms
Animals Dopamine/metabolism Glutamate Decarboxylase/genetics,metabolism In Vitro Techniques Mice Mice, Mutant Strains Microinjections Neurons/classification,cytology,drug effects,metabolism Nicotinic Agonists/administration & dosage Nicotinic Antagonists/administration & dosage Patch-Clamp Techniques Protein Subunits RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Receptors, Nicotinic/deficiency,genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction Substantia Nigra/drug effects,metabolism Tyrosine 3-Monooxygenase/genetics,metabolism Ventral Tegmental Area/drug effects,metabolism alpha7 Nicotinic Acetylcholine Receptor gamma-Aminobutyric Acid/metabolism
Chemicals
Chrna7 protein, mouse Chrna7 protein, rat Nicotinic Agonists Nicotinic Antagonists Protein Subunits RNA, Messenger Receptors, Nicotinic alpha7 Nicotinic Acetylcholine Receptor nicotinic acetylcholine receptor alpha4 subunit nicotinic receptor beta2 gamma-Aminobutyric Acid Tyrosine 3-Monooxygenase Glutamate Decarboxylase Dopamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Klink R
Laboratoire de Neurobiologie Moléculaire, Centre National de la Recherche Scientifique Unité de Recherche Associée 2182 "Récepteurs et Cognition," Institut Pasteur, 75724 Paris Cédex 15, France.
de Kerchove d'Exaerde A
Zoli M
Changeux J P
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-03-01
Pages
1452-63
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762941
Subset
IM
Grants
Telethon · D.105 · Italy
External Links
PubMed source PMC Full Text View journal details
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