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PMID:11222635
Citation |
Klink, R, de Kerchove d'Exaerde, A, Zoli, M and Changeux, JP (2001) Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J. Neurosci. 21:1452-63 |
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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. |
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Keywords |
Animals; Dopamine/metabolism; Glutamate Decarboxylase/genetics; Glutamate Decarboxylase/metabolism; Mice; Mice, Mutant Strains; Microinjections; Neurons/classification; Neurons/cytology; Neurons/drug effects; Neurons/metabolism; Nicotinic Agonists/administration & dosage; Nicotinic Antagonists/administration & dosage; Patch-Clamp Techniques; Protein Subunits; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic/deficiency; Receptors, Nicotinic/genetics; Receptors, Nicotinic/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Substantia Nigra/drug effects; Substantia Nigra/metabolism; Tyrosine 3-Monooxygenase/genetics; Tyrosine 3-Monooxygenase/metabolism; Ventral Tegmental Area/drug effects; Ventral Tegmental Area/metabolism; gamma-Aminobutyric Acid/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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