University of Bordeaux, Institut des Maladies Neurodegeneratives UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodegeneratives UMR 5293, Bordeaux, France.
Neurobiol Dis. 2013 Nov;59:151-64. doi: 10.1016/j.nbd.2013.07.014. Epub 2013 Aug 1.
There is growing evidence that Parkinson's disease, generally characterized by motor symptoms, also causes cognitive impairment such as spatial disorientation. The hippocampus is a critical structure for spatial navigation and receives sparse but comprehensive dopamine (DA) innervation. DA loss is known to be the cause of Parkinson's disease and therefore it has been hypothesized that the associated spatial disorientation could result from hippocampal dysfunction. Because DA is involved in the prediction of reward expectation, it is possible to infer that spatial disorientation in DA depleted subjects results from the loss of the ability to detect the rewarding features within the environment. Amongst hippocampal formation subdivisions, CA3 properties such as the high liability of its place fields make it a serious candidate for interfacing DA reward system and spatial information encoding. We addressed this issue using multiple electrode recordings of CA3 in normal and dopamine depleted rats performing a spatial learning in a Y-maze. Our data confirm that DA is essential to spatial learning as its depletion results in spatial impairments. The present work also shows that CA3 involvement in the detection of spatial feature contextual significance is under DA control. Finally, it also shows that CA3 contributes to the decision making processes of navigation tasks. The data also reveal a lateralization effect of DA depletion underlined by neural correlates.
越来越多的证据表明，帕金森病通常以运动症状为特征，也会导致认知障碍，如空间定向障碍。海马体是空间导航的关键结构，它接受稀疏但全面的多巴胺（DA）支配。众所周知，DA 丧失是帕金森病的原因，因此有人假设，相关的空间定向障碍可能是由于海马体功能障碍引起的。由于 DA 参与了对奖励预期的预测，因此可以推断，在 DA 耗竭的受试者中出现的空间定向障碍是由于丧失了检测环境中奖励特征的能力。在海马体结构的细分中，CA3 的特性，如其位置场的高易感性，使其成为与 DA 奖励系统和空间信息编码接口的重要候选者。我们使用正常和多巴胺耗竭大鼠在 Y 迷宫中进行空间学习时的 CA3 多电极记录来解决这个问题。我们的数据证实，DA 对空间学习至关重要，因为它的耗竭会导致空间障碍。目前的工作还表明，CA3 参与了对空间特征上下文意义的检测，这是受 DA 控制的。最后，它还表明 CA3 有助于导航任务的决策过程。数据还揭示了 DA 耗竭的偏侧化效应，这是由神经相关性强调的。
