Department of Psychology, Philipps-University of Marburg, Gutenbergstrasse18, 35032 Marburg, Germany.
Neurotox Res. 2010 Apr;17(3):287-98. doi: 10.1007/s12640-009-9103-4.
Sequential behavior has been intensively investigated in humans using so-called serial reaction time tasks(SRTT), in which visual stimuli are either presented in a random or sequential order. Typically, when the stimulus presentation follows a previously learned sequential order,reaction times are decreased compared to random stimulus presentation and become partly automated. A vast amount of SRTT findings indicates that sequential learning and performance seem to be mediated amongst others by the basal ganglia-especially the striatum-and the neurotransmitter dopamine therein. In this study we used an operant rat version of the human four choice SRTT to investigate the effect of bilateral neostriatal dopamine lesions induced by 6-hydroxydopamine on sequential learning. The rats' task was to respond rapidly to illuminated holes by nose-poking into them. During extensive training, the position of the illuminated hole followed a 12-item sequence. The outcome of this sequential training was also investigated in two tests, namely an interference test, where stimulus presentation switched between this sequential and a pseudo random order every five minutes, and a violation test, in which only one sequence item was eventually skipped. The neurotoxic lesions, which was placed before the start of training, led to the expected sub-total dopamine depletions (i.e. residual levels around 34-56% of controls), especially in the medial neostriatum. These lesions did not lead to general motor deficits in a catalepsy task, but moderate deficits in locomotion in an activity box, which largely recovered with time after lesion. In the SRTT, rats with lesions showed impaired learning, that is, less response accuracy and slower reaction times than the control group.During a subsequent test with alternating phases of sequential and random stimulus presentations, reaction times and accuracy of the control group were superior during sequential as compared to random stimulus phases. In the lesion group, only a moderate advantage in accuracy was observed. In the violation test, another outcome measure, the control group showed an expected increase in reaction times on the violated positions. By contrast, the lesion group showed no such increase, which indicates less automation of sequential behavior in these animals. For one, these findings support previous evidence in showing that neostriatal dopamine plays an important role for instrumental behavior, in general. Furthermore,and most importantly, they suggest that dopaminergic-striatal networks also play an important role in sequential behavior, especially its acquisition.
连续行为在人类中已经通过所谓的序列反应时间任务（SRTT）进行了深入研究，其中视觉刺激以随机或序列的方式呈现。通常，当刺激呈现遵循先前学习的序列顺序时，与随机刺激呈现相比，反应时间会减少，并变得部分自动化。大量 SRTT 研究结果表明，序列学习和表现似乎除其他外还受到基底神经节的介导，特别是纹状体及其内的神经递质多巴胺。在这项研究中，我们使用了人类四选择 SRTT 的操作性大鼠版本，来研究 6-羟多巴胺诱导的双侧新纹状体多巴胺损伤对序列学习的影响。大鼠的任务是通过将鼻子戳入照亮的孔中来快速响应照亮的孔。在广泛的训练过程中，照亮孔的位置遵循一个 12 项序列。在两个测试中还研究了这种序列训练的结果，即干扰测试，其中每隔五分钟在这个序列和一个伪随机顺序之间切换刺激呈现，以及违反测试，其中只有一个序列项最终被跳过。神经毒性损伤发生在训练开始之前，导致预期的多巴胺总量耗竭（即剩余水平约为对照组的 34-56%），特别是在纹状体的内侧。这些损伤不会导致在僵硬任务中出现一般运动缺陷，但在活动箱中的运动能力中会出现中度缺陷，这些缺陷在损伤后随着时间的推移而大大恢复。在 SRTT 中，损伤组的大鼠表现出学习受损，即反应准确性较低且反应时间较慢，比对照组差。在随后的具有交替顺序和随机刺激呈现阶段的测试中，对照组在顺序刺激阶段的反应时间和准确性优于随机刺激阶段。在损伤组中，仅观察到准确性的适度优势。在违反测试中，作为另一个结果测量，对照组在违反位置的反应时间增加。相比之下，损伤组没有观察到这种增加，这表明这些动物的序列行为的自动化程度较低。一方面，这些发现支持了先前的证据，表明新纹状体多巴胺对一般工具行为起着重要作用。此外，最重要的是，它们表明多巴胺纹状体网络在序列行为中也起着重要作用，特别是在其获取方面。
