Molecular and Physiological Diversity of Nicotinic Acetylcholine Receptors in the Midbrain Dopaminergic Nuclei

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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, β2−/−, α4−/−, and α7−/− mice. The eight nAChR subunits expressed in these nuclei, α3–7 and β2–4, 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-β-erythroidine (2 μm), α-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not contain the α7 subunit; it possesses a putative α4α6α5(β2)2 composition. The other subtype is inhibited by dihydro-β-erythroidine (2 μm) and has a putative α4α5(β2)2 composition. Gaba neurons in the VTA exhibit a third subtype with a putative (α4)2(β2)3 composition, whereas Gaba neurons in the SN have either the putative (α4)2(β2)3 oligomer or the putative α4α6α5(β2)2 oligomer. The fourth subtype, a putative (α7)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.