Department of Psychiatry and Behavioral Sciences, University of Southern California.
Graduate Program in Neurosciences, University of Southern California.
Neuroreport. 2020 Oct 14;31(15):1055-1064. doi: 10.1097/WNR.0000000000001509.
Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 4 weeks of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation and interventions.
背侧纹状体损伤会导致认知灵活性缺陷，这是帕金森病（PD）的早期特征，可能反映了额纹状体处理的改变。本研究旨在研究双侧背侧纹状体 6-羟多巴胺损伤大鼠的认知灵活性缺陷。虽然以前已经使用十字迷宫、T 迷宫和食物挖掘任务在啮齿类 PD 模型中检查了认知灵活性缺陷，但本研究首次使用具有反转学习的 3 选择序列反应时间任务（3-CSRT-R）检查了这种缺陷。尽管与对照组相比，损伤组在 3-CSRT 中的获得速度较慢，但经过 4 周的训练，损伤组能够获得与对照组相当的准确性。相比之下，在反转学习阶段出现了明显且持续的缺陷。我们的结果表明，在 3-CSRT-R 范式中通过反转学习可以明显揭示认知灵活性缺陷，这可以作为评估背侧纹状体去传入损伤和干预措施的有用测试。
