A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states.
A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states.
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DOI：
10.1038/s41467-018-03087-1
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发表时间：
2018-02-21
影响因子：
16.6
通讯作者：
Vanderschuren LJMJ
中科院分区：
文献类型：
--
作者：
Verharen JPH;de Jong JW;Roelofs TJM;Huffels CFM;van Zessen R;Luijendijk MCM;Hamelink R;Willuhn I;den Ouden HEM;van der Plasse G;Adan RAH;Vanderschuren LJMJ
精神障碍中的高多巴胺能状态与决策的破坏性缺陷有关。然而，地形不同的中脑多巴胺通路的决策过程的精确贡献仍然难以捉摸。在这里，我们显示，使用多学科的方法，如何从腹侧被盖区（VTA）的上行投射活动过度有助于受损的灵活决策大鼠。腹侧被盖区-丘脑核通路的激活导致对损失和惩罚的不敏感，这是由于负面奖励预测错误的处理受损。相比之下，腹侧被盖区-前额叶皮质通路的激活会促进风险决策，而不会影响选择经济上最有利的选择的能力。总之，这些研究结果显示了VTA上行投射的功能障碍如何影响基于价值的决策，这表明了一种潜在的机制，通过这种机制，前脑多巴胺信号的增加导致异常行为，如药物滥用，躁狂症和帕金森病多巴胺替代治疗后所见。多巴胺能功能异常增加导致基于价值的决策受损。在这里，作者报告了腹侧被盖区激活对大鼠灵活的基于价值的决策的不同方面的路径特异性影响。
Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA–nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA–prefrontal cortex pathway promotes risky decision making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision making, suggesting a potential mechanism through which increased forebrain dopamine signaling leads to aberrant behavior, as is seen in substance abuse, mania, and after dopamine replacement therapy in Parkinson’s disease. Aberrant increased dopaminergic function results in impaired value-based decision making. Here the authors report pathway-specific effects of VTA activation on distinct aspects of flexible value-based decisions in rats.
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