Functional Nicotinic Acetylcholine Receptors Containing Î±6 Subunits Are On Gabaergic Neuronal Boutons Adherent To Ventral Tegmental Area Dopamine Neurons
Diverse nicotinic acetylcholine receptor (nAChR) subtypes containing different subunit combinations can be placed on nerve terminals or soma/dendrites in the ventral tegmental area (VTA). nAChR Î±6 subunit message is abundant in the VTA, but Î±6*-nAChR cellular localization, function, pharmacology, and roles in cholinergic modulation of dopaminergic (DA) neurons within the VTA are not well understood. Here, we report evidence for Î±6Î²2*-nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. Î±-Conotoxin (Î±-Ctx) MII labeling coupled with immunocytochemical staining localizes putative Î±6*-nAChRs to presynaptic GABAergic boutons on acutely dissociated, rat VTA DA neurons. Functionally, acetylcholine (ACh) induces increases in the frequency of bicuculline-, picrotoxin-, and 4-aminopyridine-sensitive miniature IPSCs (mIPSCs) mediated by GABAA receptors. These increases are abolished by Î±6*-nAChR-selective Î±-Ctx MII or Î±-Ctx PIA (1 nM) but not by Î±7 (10 nM methyllycaconitine) or Î±4* (1 Î¼M dihydro-Î²-erythroidine)-nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR Î²2 knock-out mice. Moreover, ACh induces an Î±-Ctx PIA-sensitive elevation in intraterminal Ca2+ in synaptosomes prepared from the rat VTA. Subchronic exposure to 500 nM nicotine reduces ACh-induced GABA release onto the VTA DA neurons, as does 10 d of systemic nicotine exposure. Collectively, these results indicate that Î±6Î²2*-nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic Î±6Î²2*-nAChRs likely play important roles in nicotinic modulation of DA neuronal activity. Copyright Â© 2011 the authors.
Journal of Neuroscience
Digital Object Identifier (DOI)
Yang, Kechun; Buhlman, Lori; Khan, Ghous M.; Nichols, Robert A.; Jin, Guozhang; McIntosh, J. Michael; Whiteaker, Paul; Lukas, Ronald J.; and Wu, Jie, "Functional Nicotinic Acetylcholine Receptors Containing Î±6 Subunits Are On Gabaergic Neuronal Boutons Adherent To Ventral Tegmental Area Dopamine Neurons" (2011). Translational Neuroscience. 223.