TY - JOUR T1 - Functional Nicotinic Acetylcholine Receptors Containing α6 Subunits Are on GABAergic Neuronal Boutons Adherent to Ventral Tegmental Area Dopamine Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2537 LP - 2548 DO - 10.1523/JNEUROSCI.3003-10.2011 VL - 31 IS - 7 AU - Kechun Yang AU - Lori Buhlman AU - Ghous M. Khan AU - Robert A. Nichols AU - Guozhang Jin AU - J. Michael McIntosh AU - Paul Whiteaker AU - Ronald J. Lukas AU - Jie Wu Y1 - 2011/02/16 UR - http://www.jneurosci.org/content/31/7/2537.abstract N2 - 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 α6 subunit message is abundant in the VTA, but α6*–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 α6β2*–nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. α-Conotoxin (α-Ctx) MII labeling coupled with immunocytochemical staining localizes putative α6*–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 α6*–nAChR-selective α-Ctx MII or α-Ctx PIA (1 nm) but not by α7 (10 nm methyllycaconitine) or α4* (1 μm dihydro-β-erythroidine)–nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR β2 knock-out mice. Moreover, ACh induces an α-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 α6β2*–nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic α6β2*–nAChRs likely play important roles in nicotinic modulation of DA neuronal activity. ER -