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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
DOI10.1523/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
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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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