VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation
VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation
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DOI：
10.1073/pnas.0910986107
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发表时间：
2010-01-05
影响因子：
11.1
通讯作者：
Wallen-Mackenzie, Asa
中科院分区：
文献类型：
--
作者：
Birgner, Carolina;Nordenankar, Karin;Wallen-Mackenzie, Asa
在过去的三十年中，“一神经元-一神经递质”的概念经常受到挑战，神经递质在单个神经元中共存现在被认为是一种普遍现象。然而，神经递质共存的功能意义尚不清楚。一些研究表明，腹侧被盖区（VTA）的多巴胺（DA）神经元亚群表达泡状谷氨酸转运蛋白2 (VGLUT2)，并被认为使用谷氨酸作为共递质。VTA多巴胺神经元投射到包括伏隔核在内的边缘结构，并参与介导精神兴奋剂的动机和运动激活效应。为了确定这些神经元中谷氨酸共传递的功能作用，我们使用条件基因靶向方法在小鼠DA神经元中删除了VGLUT2。建立了DAT-Cre/Vglut2Lox小鼠系（Vglut2（f/f;DAT-Cre）小鼠），并通过体内电流法和几种行为范式进行了分析。尽管Vglut2（f/f;DAT-Cre）小鼠的基础运动功能正常，但它们的冒险行为发生了改变。有趣的是，在家庭笼子和新环境中，基因靶向小鼠对通过中脑DA系统起作用的精神兴奋剂安非他明表现出极大的迟钝的运动反应。我们的研究结果表明，VGLUT2在DA神经元中的表达是正常情绪反应和精神兴奋剂介导的行为激活所必需的。
The "One neuron-one neurotransmitter" concept has been challenged frequently during the last three decades, and the coexistence of neurotransmitters in individual neurons is now regarded as a common phenomenon. The functional significance of neurotransmitter coexistence is, however, less well understood. Several studies have shown that a subpopulation of dopamine (DA) neurons in the ventral tegmental area (VTA) expresses the vesicular glutamate transporter 2 (VGLUT2) and has been suggested to use glutamate as a cotransmitter. The VTA dopamine neurons project to limbic structures including the nucleus accumbens, and are involved in mediating the motivational and locomotor activating effects of psychostimulants. To determine the functional role of glutamate cotransmission by these neurons, we deleted VGLUT2 in DA neurons by using a conditional gene-targeting approach in mice. A DAT-Cre/Vglut2Lox mouse line (Vglut2(f/f;DAT-Cre) mice) was produced and analyzed by in vivo amperometry as well as by several behavioral paradigms. Although basal motor function was normal in the Vglut2(f/f;DAT-Cre) mice, their risk-taking behavior was altered. Interestingly, in both home-cage and novel environments, the gene targeted mice showed a greatly blunted locomotor response to the psychostimulant amphetamine, which acts via the midbrain DA system. Our results show that VGLUT2 expression in DA neurons is required for normal emotional reactivity as well as for psychostimulant-mediated behavioral activation.