Functional nicotinic acetylcholine receptors containing alpha 6 subunits are on gabaergic neuronal boutons adherent to ventral tegmental area dopamine neurons | |
Yang, Kechun1; Buhlman, Lori2; Khan, Ghous M.3; Nichols, Robert A.3; Jin, Guozhang4; McIntosh, J. Michael5,6; Whiteaker, Paul2; Lukas, Ronald J.2; Wu, Jie1 | |
刊名 | Journal of neuroscience |
2011-02-16 | |
卷号 | 31期号:7页码:2537-2548 |
ISSN号 | 0270-6474 |
DOI | 10.1523/jneurosci.3003-10.2011 |
通讯作者 | Wu, jie(jie.wu@chw.edu) |
英文摘要 | 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 alpha 6 subunit message is abundant in the vta, but alpha 6(star)-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 alpha 6 beta 2(star)-nachr expression on gaba neuronal boutons terminating on vta da neurons. alpha-conotoxin (alpha-ctx) mii labeling coupled with immunocytochemical staining localizes putative alpha 6(star)-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 alpha 6(star)-nachr-selective alpha-ctx mii or alpha-ctx pia (1 nm) but not by alpha 7 (10 nm methyllycaconitine) or alpha 4(star) (1 mu m dihydro-beta-erythroidine)-nachr-selective antagonists. ach also fails to increase mipsc frequency in vta da neurons prepared from nachr beta 2 knock-out mice. moreover, ach induces an alpha-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 alpha 6 beta 2(star)-nachrs are located on presynaptic gabaergic boutons within the vta and modulate gaba release onto da neurons. these presynaptic alpha 6 beta 2(star)-nachrs likely play important roles in nicotinic modulation of da neuronal activity. |
WOS关键词 | RAT-BRAIN ; SYNAPTIC MECHANISMS ; CONOTOXIN-MII ; NUCLEUS-ACCUMBENS ; SUBSTANTIA-NIGRA ; REWARD AREAS ; ADDICTION ; PHARMACOLOGY ; TRANSMISSION ; ANTAGONIST |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
语种 | 英语 |
出版者 | SOC NEUROSCIENCE |
WOS记录号 | WOS:000287392400022 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2375944 |
专题 | 武汉病毒研究所 |
通讯作者 | Wu, Jie |
作者单位 | 1.St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA 2.St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 USA 3.Univ Hawaii, Dept Physiol & Pharmacol, John A Burns Sch Med, Honolulu, HI 96813 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China 5.Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA 6.Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA |
推荐引用方式 GB/T 7714 | Yang, Kechun,Buhlman, Lori,Khan, Ghous M.,et al. Functional nicotinic acetylcholine receptors containing alpha 6 subunits are on gabaergic neuronal boutons adherent to ventral tegmental area dopamine neurons[J]. Journal of neuroscience,2011,31(7):2537-2548. |
APA | Yang, Kechun.,Buhlman, Lori.,Khan, Ghous M..,Nichols, Robert A..,Jin, Guozhang.,...&Wu, Jie.(2011).Functional nicotinic acetylcholine receptors containing alpha 6 subunits are on gabaergic neuronal boutons adherent to ventral tegmental area dopamine neurons.Journal of neuroscience,31(7),2537-2548. |
MLA | Yang, Kechun,et al."Functional nicotinic acetylcholine receptors containing alpha 6 subunits are on gabaergic neuronal boutons adherent to ventral tegmental area dopamine neurons".Journal of neuroscience 31.7(2011):2537-2548. |
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