Diversity and distribution of nicotinic acetylcholine receptors in the locus ceruleus neurons

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% (alpha 2). Yet, two populations of neurons could be distinguished on the basis of the pattern of expression of nAChR mRNAs and eletrophysiological properties. One population (type A) of small cells systematically expressed alpha 3 and beta 4 mRNAs (and often alpha 6, beta 3, alpha 5, alpha 4), and nicotinic agonists elicited large currents with a potency order of cytisine > nicotine. Another population (type 8) of cells with large soma did not contain alpha 3 and beta 4 mRNAs but, systematically, alpha 6 and beta 3 (and often alpha 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 8 cells of the locus ceruleus. Accordingly, immunocytochemical labeling showed that beta 3 is present in hippocampal terminals. The alpha 6 beta 3 beta 2(alpha 4) heterooligomer thus behaves as the main nicotinic regulator of the ceruleo-hippocampal pathway.