Stimulation of cortical acetylcholine release by orexin A

Stimulation of cortical acetylcholine release by orexin A
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DOI:
10.1016/j.neuroscience.2004.09.050
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发表时间:
2005-01-01
期刊:
影响因子:
3.3
通讯作者:
Reznikov, LR
Reznikov, LR
中科院分区:
医学3区
文献类型:
--
作者:
Fadel, J;Pasumarthi, R;Reznikov, LR

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基底前脑胆碱能系统是注意功能神经生物学底物的重要组成部分。食欲素神经元对觉醒和保持清醒很重要,以前发现在下丘脑的区域投射到基底前脑。我们在大鼠体内使用双探针微透析来验证增食欲素A(OXA)增加皮质乙酰胆碱(ACh)释放的假说。基底动脉注射OXA(0、0.1、10.0um通过反向透析)可剂量依赖性地增加前额叶皮质(PFC)ACh的释放。在另一组动物中,通过反向透析局部(PFC内)给药OXA对ACh的释放没有显著影响。为了从解剖学上证实基底前脑是增食欲素调节皮质顶叶胆碱能活动的部位,我们用免疫组织化学方法研究了基底前脑中增食欲素纤维与胆碱能神经元之间的关系。我们观察到食欲素免疫反应纤维广泛分布在基底前脑的胆碱能区,特别是在更靠前的区域,在那里经常观察到食欲素纤维与胆碱乙酰转移酶阳性细胞体之间明显的对位接触。总而言之,这些数据表明,食欲素投射到基底前脑形成了下丘脑觉醒和前脑注意系统之间的重要联系。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
The basal forebrain cholinergic system is a critical component of the neurobiological substrates underlying attentional function. Orexin neurons are important for arousal and maintenance of wakefulness and are found in the area of the hypothalamus previously shown to project to the basal forebrain. We used dual-probe in vivo microdialysis in rats to test the hypothesis that orexin A (OxA) increases cortical acetylcholine (ACh) release. Intrabasalis administration of OxA (0, 0.1, 10.0 muM via reverse dialysis) dose-dependently increased ACh release within the prefrontal cortex (PFC). In a separate group of animals, local (intra-PFC) administration of OxA via reverse dialysis was found to have no significant effect on ACh release. In order to obtain anatomical corroboration of the basal forebrain as a site of orexin modulation of corticopetal cholinergic activity, we used immunohistochemistry to examine the relationship between orexin fibers and cholinergic neurons in the basal forebrain. We observed widespread distribution of orexin-immunoreactive fibers in cholinergic regions of the basal forebrain, particularly in more rostral areas where frequent instances of apparent appositional contact were observed between orexin fibers and choline acetyltransferase-positive cell bodies. Collectively, these data suggest that orexin projections to the basal forebrain form an important link between hypothalamic arousal and forebrain attentional systems. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.