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Essential role of neocortical acetylcholine in spatial memory.

机译:新皮质乙酰胆碱在空间记忆中的重要作用。

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The cholinergic system plays a crucial role in learning and memory. Lesions of cholinergic nuclei, pharmacological manipulations of cholinergic systems, intracerebral transplantation of fetal tissue and anatomical changes in cholinergic pathways during ageing have all been correlated with altered cognitive behaviour. However, it has not been proved that regional acetylcholine is causally required for learning and memory. Here we describe how we achieved a permanent and selective impairment of learning and memory by damaging the nucleus basalis magnocellularis, a nucleus that provides the major cholinergic innervation of the neocortex, in adult rats. To test the hypothesis that acetylcholine is essential for restoration of cognitive function, we implanted genetically modified cells that produce acetylcholine into denervated neocortical target regions. After grafting, rats with increased neocortical acetylcholine levels showed a significant improvement in a spatial navigation task. Acetylcholine is thus not only necessary for learning and memory, as previously argued, but its presence within the neocortex is also sufficient to ameliorate learning deficits and restore memory following damage to the nucleus basalis.
机译:胆碱能系统在学习和记忆中起着至关重要的作用。衰老过程中胆碱能细胞核的损伤,胆碱能系统的药理学操作,胎儿组织的脑内移植以及胆碱能途径的解剖学改变都与认知行为改变有关。然而,尚未证明区域性乙酰胆碱是学习和记忆的因果关系。在这里,我们描述了如何通过损伤成年大鼠基底皮层的大细胞核(提供新皮层主要胆碱能神经支配的神经核)来实现学习和记忆的永久性和选择性损伤。为了检验乙酰胆碱对于恢复认知功能必不可少的假设,我们将产生乙酰胆碱的基因修饰细胞植入到失神经的新皮层靶区域。移植后,新皮质乙酰胆碱水平增加的大鼠在空间导航任务中显示出显着改善。因此,如前所述,乙酰胆碱不仅是学习和记忆所必需的,而且它在新皮层中的存在也足以缓解学习障碍并在基底核受损后恢复记忆。

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