Selective Effects of the Loss of NMDA or mGluR5 Receptors in the Reward System on Adaptive Decision-Making.
Selective Effects of the Loss of NMDA or mGluR5 Receptors in the Reward System on Adaptive Decision-Making.
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DOI：
10.1523/eneuro.0331-18.2018
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发表时间：
2018-07
期刊：
影响因子：
3.4
通讯作者：
Rodriguez Parkitna J
中科院分区：
文献类型：
--
作者：
Cieślak PE;Ahn WY;Bogacz R;Rodriguez Parkitna J
在不断变化的环境中选择最有利的行动是适应性行为的核心特征。中脑多巴胺(DA)神经元及其主要投射靶点，包括额叶皮质和基底节的多巴胺感受性神经元，在这一过程中起着关键作用。在这里，我们研究了多巴胺系统中NMDA受体和代谢性谷氨酸受体5(MGluR5)选择性遗传中断对小鼠适应性选择行为的影响。我们测试了突变对概率强化学习和概率折扣任务的性能的影响。在概率选择的情况下，无论是多巴胺能神经元中NMDA受体的丢失，还是表达D1受体的多巴胺能神经元中mGluR5受体的丢失，都降低了选择更有回报的替代方案的可能性，并降低了返回到先前获得回报的替代方案(Win-Stay)的可能性。当观察到的行为符合强化学习模型时，我们发现这两个突变与预期结果对选择的影响降低(即更多的随机选择)有关。这些突变都没有影响概率折扣，这表明所有动物都具有正常的评估概率的能力。然而，在这两种行为任务中，多巴胺能神经元中NMDA受体的靶向缺失或D1神经元中mGluR5受体的靶向缺失的动物执行选择的速度明显较慢。综上所述，这些结果表明，DA系统中的谷氨酸受体依赖的信号对于选择的速度和准确性是必不可少的，但同时对于正确估计可能的结果可能不是关键。
Selecting the most advantageous actions in a changing environment is a central feature of adaptive behavior. The midbrain dopamine (DA) neurons along with the major targets of their projections, including dopaminoceptive neurons in the frontal cortex and basal ganglia, play a key role in this process. Here, we investigate the consequences of a selective genetic disruption of NMDA receptor and metabotropic glutamate receptor 5 (mGluR5) in the DA system on adaptive choice behavior in mice. We tested the effects of the mutation on performance in the probabilistic reinforcement learning and probability-discounting tasks. In case of the probabilistic choice, both the loss of NMDA receptors in dopaminergic neurons or the loss mGluR5 receptors in D1 receptor-expressing dopaminoceptive neurons reduced the probability of selecting the more rewarded alternative and lowered the likelihood of returning to the previously rewarded alternative (win-stay). When observed behavior was fitted to reinforcement learning models, we found that these two mutations were associated with a reduced effect of the expected outcome on choice (i.e., more random choices). None of the mutations affected probability discounting, which indicates that all animals had a normal ability to assess probability. However, in both behavioral tasks animals with targeted loss of NMDA receptors in dopaminergic neurons or mGluR5 receptors in D1 neurons were significantly slower to perform choices. In conclusion, these results show that glutamate receptor-dependent signaling in the DA system is essential for the speed and accuracy of choices, but at the same time probably is not critical for correct estimation of probable outcomes.