Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention
Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention
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DOI：
10.1093/cercor/bhh202
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发表时间：
2005-07-01
期刊：
影响因子：
3.7
通讯作者：
Schmauss, C
中科院分区：
文献类型：
--
作者：
Glickstein, SB;DeSteno, DA;Schmauss, C
对缺乏多巴胺D - 2和D - 3受体的小鼠以及野生型同窝小鼠进行了一项二选一知觉辨别测试，该测试依赖于前额叶皮层的最佳功能。两种突变体在关注知觉刺激或在刺激维度之间转移注意力方面均未表现出缺陷。然而，两种突变体在不同测试阶段的表现与野生型不同。D - 2突变体在首次复合辨别中表现出明显损伤，表明在任务控制规则的初始习得方面存在缺陷。相比之下，D - 3突变体在需要反转学习的定势转移阶段表现明显更好。D - 3突变体较高的反应准确性还伴随着反应潜伏期的显著延长。对测试诱导的前扣带回以及前边缘/下边缘皮层神经元中c - fos基因表达的体视学评估显示，D - 3突变体的激活程度最高，野生型处于中间，D - 2突变体最低，这表明认知测试中的反应准确性与前额叶皮层激活程度相关，无论哪些测试阶段表现出不同的性能。该研究表明，在需要注意力的任务中，多巴胺根据被激活的类D - 2受体的类型，对前额叶皮层活动有不同的调节作用。
Mice lacking dopamine D-2 and D-3 receptors and wildtype littermates were tested in a two-choice perceptual discrimination test that is dependent upon optimal functioning of the prefrontal cortex. Both mutants showed no deficits in attending to the perceptual stimuli or in shifting attention between stimulus dimensions. However, the performance of both mutants differed from the wildtype in different test phases. D-2 mutants exhibited significant impairment in the first compound discrimination, indicating deficits in the initial acquisition of the task-governing rules. In contrast, D-3 mutants performed significantly better in a set-shifting phase that required reversal learning. The higher response accuracy of D-3 mutants was also accompanied by significantly increased response latency. A stereological assessment of test-induced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D-3 mutants, intermediate activation in wildtype and lowest activation in D-2 mutants, indicating that response accuracy in the cognitive test correlates with the magnitude of prefrontal cortical activation regardless of which test phases revealed different performances. The study illustrates that dopamine differentially modulates prefrontal cortical activity during tasks requiring attention depending upon the type of D-2-like receptor that is activated.