Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory
Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory
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DOI：
10.1523/jneurosci.1885-08.2008
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发表时间：
2008-07-30
影响因子：
5.3
通讯作者：
Kirik, Deniz
中科院分区：
文献类型：
--
作者：
Wisman, Liselijn A. B.;Sahin, Gurdal;Kirik, Deniz
尽管帕金森病是一种运动障碍，但在许多患者中，认知功能障碍是一个重要的临床体征。目前还不清楚这是否仅仅是由于多巴胺水平的下降，或者其他神经递质系统是否也可能参与其中。在本研究中，使用特定的病变范例在一个或两个系统的学习和记忆能力的调节中的mesocorticolimbic多巴胺通路的重要性和可能的收敛与前脑胆碱能投射到新皮层和海马进行了研究。腹侧被盖区多巴胺能神经元的损伤导致在参考记忆任务中的表现受损，而在Morris水迷宫中，工作记忆任务的执行似乎不受影响。对游泳路径的分析显示，多巴胺耗尽的动物能够在给定的测试日调整搜索策略，但未能将此信息转移到第二天，这表明信息存储和/或回忆的缺陷。相比之下，胆碱能损伤单独没有影响，在所有的测试范例。然而，当多巴胺和乙酰胆碱耗尽时，动物在工作记忆任务中也受到损害，这表明来自这些系统的输入的功能收敛对于获得空间记忆至关重要。有趣的是，这样一个额外的收购赤字出现后，海马胆碱能耗尽无论同时中断基底皮质胆碱能传入。因此，胆碱能改变的进一步分析可能有助于更好地理解帕金森病的认知症状。
Although Parkinson's disease is a movement disorder, in many patients cognitive dysfunction is an important clinical sign. It is not yet clear whether this is attributable solely to a decrease in dopamine levels, or whether other neurotransmitter systems might be involved as well. In the present study, the importance of the mesocorticolimbic dopamine pathway and a possible convergence with forebrain cholinergic projections to neocortex and hippocampus in the regulation of learning and memory abilities were investigated by using specific lesion paradigms in one or both systems. Lesioning of dopaminergic neurons in the ventral tegmental area resulted in an impaired performance in the reference memory task, whereas the execution of the working memory tasks appeared to be unaffected in the Morris water maze. Analysis of the swim paths revealed that the dopamine-depleted animals were capable of adapting a search strategy on a given testing day but failed to transfer this information to the next day, suggesting a deficit in information storage and/or recall. In contrast, cholinergic lesions alone were without effect in all test paradigms. However, when both dopamine and acetylcholine were depleted, animals were also impaired in the working memory task, indicating that a functional convergence of the inputs from these systems was critical for acquisition of spatial memory. Interestingly, such an additional acquisition deficit appeared only after hippocampal cholinergic depletion regardless of a concurrent disruption of basalocortical cholinergic afferents. Thus, further analyses of cholinergic alterations may prove useful in better understanding the cognitive symptoms in Parkinson's disease.