Cognitive Flexibility Deficits Following 6-OHDA Lesions of the Rat Dorsomedial Striatum
Cognitive Flexibility Deficits Following 6-OHDA Lesions of the Rat Dorsomedial Striatum
复制标题
DOI：
10.1016/j.neuroscience.2018.01.032
复制
发表时间：
2018-03-15
期刊：
影响因子：
3.3
通讯作者：
Ragozzino, Michael E.
中科院分区：
文献类型：
--
作者：
Grospe, Gena M.;Baker, Phillip M.;Ragozzino, Michael E.
帕金森病（PD）是一种神经退行性疾病，其特征是严重的运动缺陷和纹状体多巴胺水平降低。PD患者还通常表现出认知灵活性损伤，例如，概率逆转学习缺陷限制了日常生活。然而，关于纹状体多巴胺信号的减少如何影响认知灵活性的知之甚少。过去的研究表明，大鼠背内侧纹状体是支持认知灵活性的纹状体亚区。由于PD患者表现出概率性逆转学习缺陷，本实验研究了神经毒素6-羟基多巴胺（6-OHDA）注射到雄性Long-Evans大鼠的背内侧纹状体中是否会影响使用概率学习程序（80/20）的空间辨别的获得和/或逆转学习。在交叉迷宫中进行行为测试，连续两天进行。与假手术对照组相比，6-OHDA损伤的大鼠在获得时没有受损，但在逆转学习中受损。在反向学习中，背内侧纹状体多巴胺耗竭导致先前正确选择模式的初始持续，以及在最初选择后维持新选择模式（回归错误）的障碍。背内侧纹状体中的6-OHDA损伤也显著增加了逆转学习中的“丢失移位”概率，这表明该纹状体区域中多巴胺信号的减少增加了对负反馈的敏感性，最终损害了新反应模式的维持。总的来说，研究结果表明，多巴胺减少在这个纹状体亚区可以作为一个有用的模型来测试新的治疗方法，改善认知灵活性缺陷的PD。(C)2018作者（S）由Elsevier Ltd代表IBRO出版。
Parkinson's disease (PD) is a neurodegenerative disorder marked by severe motor deficits and reduced striatal dopamine levels. PD patients also commonly exhibit cognitive flexibility impairments, e.g., probabilistic reversal learning deficits that limit daily living. However, less is known about how decreased striatal dopamine signaling affects cognitive flexibility. Past studies indicate that the rat dorsomedial striatum is a striatal subregion that supports cognitive flexibility. Because PD patients exhibit probabilistic reversal learning deficits, the present experiment investigated whether the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the dorsomedial striatum of male Long-Evans rats affects the acquisition and/or reversal learning of a spatial discrimination using a probabilistic learning procedure (80/20). Behavioral testing was conducted in a cross maze that occurred across two consecutive days. Rats with 6-OHDA lesions were not impaired on acquisition, but were impaired in reversal learning compared to that of sham controls. In reversal learning, dorsomedial striatal dopamine depletion led to initial perseveration of the previously correct choice pattern, as well as an impairment in maintaining the new choice pattern after initially selected (regressive errors). A 6-OHDA lesion in the dorsomedial striatum also significantly increased 'lose-shift' probabilities in reversal learning suggesting that reduced dopamine signaling in this striatal area increased sensitivity to negative feedback ultimately impairing the maintenance of a new response pattern. Overall, the findings suggest that dopamine reduction in this striatal subregion can serve as a useful model to test novel treatments for ameliorating cognitive flexibility deficits in PD. (C) 2018 The Author(s). Published by Elsevier Ltd on behalf of IBRO.