Dept. of Neurobiology and Anatomy, Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston Salem, NC 27157, USA.
J Neurophysiol. 2011 Nov;106(5):2180-8. doi: 10.1152/jn.00148.2011. Epub 2011 Jul 27.
The prefrontal cortex, a cortical area essential for working memory and higher cognitive functions, is modulated by a number of neurotransmitter systems, including acetylcholine; however, the impact of cholinergic transmission on prefrontal activity is not well understood. We relied on systemic administration of a muscarinic receptor antagonist, scopolamine, to investigate the role of acetylcholine on primate prefrontal neuronal activity during execution of working memory tasks and recorded neuronal activity with chronic electrode arrays and single electrodes. Our results indicated a dose-dependent decrease in behavioral performance after scopolamine administration in all the working memory tasks we tested. The effect could not be accounted for by deficits in visual processing, eye movement responses, or attention, because the animals performed a visually guided saccade task virtually error free, and errors to distracting stimuli were not increased. Performance degradation under scopolamine was accompanied by decreased firing rate of the same cortical sites during the delay period of the task and decreased selectivity for the spatial location of the stimuli. These results demonstrate that muscarinic blockade impairs performance in working memory tasks and prefrontal activity mediating working memory.
前额叶皮层是工作记忆和高级认知功能所必需的皮质区域，它受到多种神经递质系统的调节，包括乙酰胆碱；然而，胆碱能传递对前额叶活动的影响还不是很清楚。我们依赖于全身给予毒蕈碱受体拮抗剂东莨菪碱，来研究乙酰胆碱在执行工作记忆任务时对灵长类动物前额叶神经元活动的作用，并使用慢性电极阵列和单电极记录神经元活动。我们的结果表明，在我们测试的所有工作记忆任务中，东莨菪碱给药后行为表现呈剂量依赖性下降。这种效应不能用视觉处理、眼球运动反应或注意力缺陷来解释，因为动物执行了一个几乎没有错误的视觉引导的扫视任务，并且对分心刺激的错误没有增加。在东莨菪碱作用下，性能下降伴随着任务延迟期间相同皮质部位的放电率降低，以及对刺激空间位置的选择性降低。这些结果表明，毒蕈碱阻断会损害工作记忆任务的表现，并影响工作记忆的前额叶活动。
