Yang_2011_J.Neurosci_31_2537

Reference

Title : Functional nicotinic acetylcholine receptors containing alpha6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons - Yang_2011_J.Neurosci_31_2537
Author(s) : Yang K , Buhlman L , Khan GM , Nichols RA , Jin G , McIntosh JM , Whiteaker P , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 31 :2537 , 2011
Abstract :

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 alpha6 subunit message is abundant in the VTA, but alpha6*-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 alpha6beta2*-nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. alpha-Conotoxin (alpha-Ctx) MII labeling coupled with immunocytochemical staining localizes putative alpha6*-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 GABA(A) receptors. These increases are abolished by alpha6*-nAChR-selective alpha-Ctx MII or alpha-Ctx PIA (1 nm) but not by alpha7 (10 nm methyllycaconitine) or alpha4* (1 mum dihydro-beta-erythroidine)-nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR beta2 knock-out mice. Moreover, ACh induces an alpha-Ctx PIA-sensitive elevation in intraterminal Ca(2+) 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 alpha6beta2*-nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic alpha6beta2*-nAChRs likely play important roles in nicotinic modulation of DA neuronal activity.

PubMedSearch : Yang_2011_J.Neurosci_31_2537
PubMedID: 21325521

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Citations formats

Yang K, Buhlman L, Khan GM, Nichols RA, Jin G, McIntosh JM, Whiteaker P, Lukas RJ, Wu J (2011)
Functional nicotinic acetylcholine receptors containing alpha6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons
Journal of Neuroscience 31 :2537

Yang K, Buhlman L, Khan GM, Nichols RA, Jin G, McIntosh JM, Whiteaker P, Lukas RJ, Wu J (2011)
Journal of Neuroscience 31 :2537