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, Ca2+-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.

中文翻译：

中枢神经系统中的多巴胺能信号传导调节动物行为的几个方面。在多巴胺能回路中，可以通过多巴胺受体D1或D2受体（D1Rs或D2Rs）的表达来区分两类神经元。值得注意的是，Ca 2+缺乏GluA2的可渗透GluA2谷氨酸AMPA受体（CP-AMPARs）对于控制神经元中突触可塑性和基因表达非常重要，尤其是在纹状体中的表达会影响各种形式的动物行为。但是，尚未解决D1R或D2R神经元中缺少GluA2的AMPAR对动物行为的不同影响。在这里，我们采用Cre-Lox重组系统选择性去除D1R或D2R神经元中的GluA2以表达CP-AMPAR，并进行了多种行为分析。首先，开放式实验表明D2R GluA2基因敲除（KO）小鼠表现出机能减退，而D1R神经元中的GluA2 KO对运动活性没有影响。我们还发现，与对照组相比，D1R GluA2 KO小鼠在加速旋转试验中显示出学习延迟，而D2R GluA2 KO动物表现出完全丧失运动学习能力。在社交能力测试中，D1R神经元中缺少GluA2的AMPAR表达诱导了超社交能力，而D2R GluA2 KO小鼠引起了社交能力的丧失。与对照动物相比，D1R和D2R GluA2 KO小鼠消耗的食物更少，而D1R GluA2 KO动物显示出明显更多的体重增加。最后，D1R GluA2 KO诱导了抗抑郁作用，而D2R神经元中缺少GluA2的AMPAR表达促进了抑郁样行为。两者合计，D1R和D2R神经元中缺少GluA2的CP-AMPAR表达差异地影响动物行为。与对照动物相比，D1R和D2R GluA2 KO小鼠消耗的食物更少，而D1R GluA2 KO动物显示出明显更多的体重增加。最后，D1R GluA2 KO诱导了抗抑郁作用，而D2R神经元中缺少GluA2的AMPAR表达促进了抑郁样行为。两者合计，D1R和D2R神经元中缺少GluA2的CP-AMPAR表达差异地影响动物行为。与对照动物相比，D1R和D2R GluA2 KO小鼠消耗的食物更少，而D1R GluA2 KO动物显示出明显更多的体重增加。最后，D1R GluA2 KO诱导了抗抑郁作用，而D2R神经元中缺少GluA2的AMPAR表达促进了抑郁样行为。两者合计，D1R和D2R神经元中缺少GluA2的CP-AMPAR表达差异地影响动物行为。