nature20121220-11

来自瑞士日内瓦大学的研究人员日前发现源自腹侧被盖区的投射至伏核的可释放GABA的神经元可以阻断胆碱能纹状体中间神经元的激发,从而影响小鼠的学习过程。

-2012年12月20日《自然》


中文翻译


【题目】腹侧被盖区GABA投射中止伏隔核胆碱能中间神经元以增强联想学习

【译文】腹侧被盖区(VTA)和伏核(NAc)对于学习与激发性相关结果相关的环境刺激至关重要。这类事件(奖励和反感)从VTA到NAc的信号任务主要归因于多巴胺神经元。VTA也含有可释放GABA(γ-氨基丁酸)的神经元,这种神经元提供了局部抑制,也投射到NAc。然而,这种远程抑制性投射的细胞靶点和功能重要性尚不明确。本研究表明投射至NAc的VTA中释放GABA的神经元(VTA GABA 投射神经元)可抑制纹状体胆碱能中间神经元(CINs)以增强刺激-结果学习。结合光遗传学和结构成像以及电生理学技术,我们发现VTA GABA投射神经元选择性靶向NAc CIN,形成可产生抑制性突触后电流的多重对称突触连接。这很明显,CIN是所有纹状体神经元的较小群体,在NAc中提供了胆碱能信号的主要来源。这种投射的活化足以中止NAc CIN的自发性活动,组成了动物学习刺激-结果相关性中的暂停记录。确实,我们发现在行为小鼠中强制CIN中止可以增强激发性重要刺激的辨别,这种刺激与反感结果相关。我们的结果证实VTA GABA投射神经元通过它们纹状体CIN的选择性靶向作用,提供了新的路径,即VTA与NAc显著联系。VTA GABA投射神经元因此成为NAc中多巴胺能和胆碱能调控的精心安排因子。

英文原稿


[Title]: Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning

[Authors]:Matthew T. C. Brown,1, 3 Kelly R. Tan,1, 3 Eoin C. O’Connor,1, 3 Irina Nikonenko,1 Dominique Muller1 & Christian Lüscher1, 2

[Abstract]The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also contains GABA (γ-aminobutyric acid)-releasing neurons, which provide local inhibition and also project to the NAc. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus–outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus–outcome associations. Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.

原文地址

http://www.nature.com/nature/journal/v492/n7429/full/nature11657.html

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201302/nature-ventral-tegmental-area-nucleus-accumbens-vta-gaba/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


六 × 3 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息