Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Neuroscience. 2019 Feb 1;398:102-112. doi: 10.1016/j.neuroscience.2018.12.002. Epub 2018 Dec 8.
Dopaminergic signaling in the central nervous system regulates several aspects of animal behavior. In the dopaminergic circuits, there are two classes of neurons that can be differentiated by their expression of dopamine receptors, D1 or D2 receptors (D1Rs or D2Rs). Notably, Ca-permeable GluA2-lacking glutamate AMPA receptors (CP-AMPARs) are important for gating synaptic plasticity and gene expression in neurons, and their expression particularly in the striatum affects various forms of animal behavior. However, differential effects of GluA2-lacking AMPARs in D1R or D2R neurons on animal behavior have not been addressed. Here, we employed the Cre-Lox recombination system to remove GluA2 selectively in D1R or D2R neurons to express CP-AMPARs and carried out multiple behavior assays. First, the open-field assay revealed that D2R GluA2 knockout (KO) mice showed hypoactivity, while GluA2 KO in D1R neurons had no effect on locomotor activity. We also revealed that D1R GluA2 KO mice showed delayed learning in the accelerating rotarod test compared with control animals, whereas D2R GluA2 KO animals exhibited complete loss of motor learning. In the sociability test, GluA2-lacking AMPAR expression in D1R neurons induced hypersociability, whereas D2R GluA2 KO mice elicited loss of sociability. Both D1R and D2R GluA2 KO mice consumed less food compared with control animals, while D1R GluA2 KO animals showed significantly more weight gain. Finally, D1R GluA2 KO induced anti-depressant effects, while GluA2-lacking AMPAR expression in D2R neurons promoted depression-like behavior. Taken together, GluA2-lacking CP-AMPAR expression in D1R and D2R neurons differentially affects animal behavior.
中枢神经系统中的多巴胺能信号调节动物行为的多个方面。在多巴胺能回路中，有两类神经元可以通过其多巴胺受体的表达来区分，即 D1 或 D2 受体（D1Rs 或 D2Rs）。值得注意的是，钙通透性缺失 GluA2 的谷氨酸 AMPA 受体（CP-AMPARs）对于神经元中的突触可塑性和基因表达至关重要，其在纹状体中的表达尤其影响各种形式的动物行为。然而，D1R 或 D2R 神经元中缺失 GluA2 的 AMPARs 对动物行为的影响尚未得到解决。在这里，我们使用 Cre-Lox 重组系统选择性地去除 D1R 或 D2R 神经元中的 GluA2 以表达 CP-AMPARs，并进行了多项行为分析。首先，旷场实验显示 D2R GluA2 敲除（KO）小鼠表现出活动减少，而 D1R 神经元中的 GluA2 KO 对运动活动没有影响。我们还发现 D1R GluA2 KO 小鼠在加速转棒测试中表现出学习延迟，而 D2R GluA2 KO 动物则完全丧失了运动学习能力。在社交性测试中，D1R 神经元中缺失 GluA2 的 AMPAR 表达诱导了过度社交行为，而 D2R GluA2 KO 小鼠则表现出社交行为丧失。与对照动物相比，D1R 和 D2R GluA2 KO 小鼠的食物消耗均减少，而 D1R GluA2 KO 动物的体重增加更为显著。最后，D1R GluA2 KO 诱导抗抑郁作用，而 D2R 神经元中缺失 GluA2 的 AMPAR 表达促进了抑郁样行为。总之，D1R 和 D2R 神经元中缺失 GluA2 的 CP-AMPAR 表达对动物行为有不同的影响。
