期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1999
卷号:96
期号:21
页码:12126-12131
DOI:10.1073/pnas.96.21.12126
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:The neurons of the locus ceruleus are responsible for most of the noradrenergic innervation in the brain and nicotine potentiates noradrenaline release from their terminals. Here we investigated the diversity and subcellular distribution of nicotinic acetylcholine receptors (nAChRs) in the locus ceruleus both somatically, by combining single-cell reverse transcription-PCR with electrophysiological characterization, and at the level of nerve terminals, by conducting noradrenaline efflux experiments. The proportion of neurons in the locus ceruleus expressing the nicotinic subunit mRNAs varied from 100% ({beta}2) to 3% (2). Yet, two populations of neurons could be distinguished on the basis of the pattern of expression of nAChR mRNAs and electrophysiological properties. One population (type A) of small cells systematically expressed 3 and {beta}4 mRNAs (and often 6, {beta}3, 5, 4), and nicotinic agonists elicited large currents with a potency order of cytisine > nicotine. Another population (type B) of cells with large soma did not contain 3 and {beta}4 mRNAs but, systematically, 6 and {beta}3 (and often 4) and responded to nicotinic agonists in the order of nicotine > cytisine. The nicotinic modulation of noradrenaline release in the hippocampus displayed an order of potency nicotine > cytisine, suggesting that noradrenergic terminals in the hippocampus originate largely from type B cells of the locus ceruleus. Accordingly, immunocytochemical labeling showed that {beta}3 is present in hippocampal terminals. The 6{beta}3{beta}2(4) heterooligomer thus behaves as the main nicotinic regulator of the ceruleo-hippocampal pathway.