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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation
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VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation

机译：多巴胺神经元中的VGLUT2是刺激性药物诱发的行为激活所必需的

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摘要

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.
机译：在过去的三十年中，“一个神经元一个神经递质”的概念受到了经常性的挑战，单个神经元中神经递质的共存现在被认为是一种普遍现象。然而，对神经递质共存的功能意义了解得很少。几项研究表明，腹侧被盖区（VTA）中的多巴胺（DA）神经元亚群表达了囊状谷氨酸转运蛋白2（VGLUT2），并建议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的边缘结构，并参与介导精神刺激药的动机和运动激活作用。为了确定这些神经元谷氨酸共传递的功能作用，我们通过在小鼠中使用条件基因靶向方法删除了DA神经元中的VGLUT2。产生了DAT-Cre / Vglut2Lox小鼠品系（Vglut2〜（f / f; DAT-Cre）小鼠），并通过体内安培法以及几种行为范例进行了分析。尽管Vglut2〜（f / f; DAT-Cre）小鼠的基础运动功能正常，但其冒险行为已改变。有趣的是，在笼养和新型环境中，靶向基因的小鼠对通过中脑DA系统起作用的精神刺激性苯丙胺的运动反应都大大减弱。我们的结果表明，DA神经元中的VGLUT2表达是正常情绪反应以及精神刺激剂介导的行为激活所必需的。

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    Carolina Birgner; Karin Nordenankar; Martin Lundblad; Jose Alfredo Mendez; Casey Smith; Madeleine le Greves; Dagmar Galter; Lars Olson; Anders Fredriksson; Louis-Eric Trudeau; Klas Kullander; Asa Wallen-Mackenzie;

  • 作者单位

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden Department of Pharmacology, Faculty of Medicine, Universite de Montreal, H3C 3J7 Montreal, Canada;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Unit of Pharmacology, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden;

    Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden;

    Unit of Psychiatry, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Department of Pharmacology, Faculty of Medicine, Universite de Montreal, H3C 3J7 Montreal, Canada;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden;

    Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden Department of Neuroscience, Unit of Developmental Genetics, Box 593, Biomedical Center, Uppsala University, 5-751 24 Uppsala, Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    amphetamine midbrain neurotransmission; reward; striatum;

    机译：苯丙胺中脑神经传递;奖励;纹状体;

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