Functional Nicotinic Acetylcholine Receptors Containing alpha 6 Subunits Are on GABAergic Neuronal Boutons Adherent to Ventral Tegmental Area Dopamine Neurons
文献类型：期刊论文
| 作者 | Yang, Kechun3; Buhlman, Lori6; Khan, Ghous M.1; Nichols, Robert A.1; Jin, Guozhang2 ; McIntosh, J. Michael4,5; Whiteaker, Paul6; Lukas, Ronald J.6; Wu, Jie3
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| 刊名 | JOURNAL OF NEUROSCIENCE
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| 出版日期 | 2011-02-16 |
| 卷号 | 31期号:7页码:2537-2548 |
| ISSN号 | 0270-6474 |
| DOI | 10.1523/JNEUROSCI.3003-10.2011 |
| 文献子类 | Article |
| 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 |
| 资助项目 | Arizona Biomedical Research Commission[0028] ; Arizona Biomedical Research Commission[0057] ; Institute for Mental Health Research[00000000] ; Philip Morris International External Research Program[00000000] ; Barrow Neurological Foundation[00000000] ; National Institutes of Health[NS040417] ; National Institutes of Health[DA015389] ; National Institutes of Health[DA012242] ; National Institutes of Health[MH053631] ; National Institutes of Health[GM048677] ; National Institutes of Health[AG021586] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000287392400022 |
| 出版者 | SOC NEUROSCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278600]  |
| 专题 | 院士及顾问专家 |
| 通讯作者 | Wu, Jie |
| 作者单位 | 1.Univ Hawaii, Dept Physiol & Pharmacol, John A Burns Sch Med, Honolulu, HI 96813 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China; 3.St Josephs Hosp, Barrow Neurol Inst, Div Neurol, Phoenix, AZ 85013 USA; 4.Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA; 5.Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA 6.St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 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. |
入库方式： OAI收割
来源：上海药物研究所
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