Chen Katy C, Baxter Mark G, Rodefer Joshua S
Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
Eur J Neurosci. 2004 Aug;20(4):1081-8. doi: 10.1111/j.1460-9568.2004.03548.x.
Impairments in multiple aspects of attentional and executive function follow damage to cholinergic neurons in the central nervous system. Affective and attentional set-shifting represent two aspects of executive function controlled by different sectors of the prefrontal cortex. The involvement of cholinergic neural mechanisms in these aspects of executive function has not been specified. To determine whether central muscarinic cholinergic receptors were involved in affective and/or attentional set-shifting, we tested rats on a series of discrimination learning problems, which included affective (reversal learning) and attentional set (extradimensional shift)-shifting components, under the systemic influence of scopolamine, a muscarinic antagonist. Scopolamine impaired both reversal learning and extradimensional shifting, but was without effect on learning new discrimination problems that did not require an affective or attentional shift. Systemic administration of methylscopolamine, which does not cross the blood-brain barrier, did not impair affective or attentional set-shifting, indicating that the scopolamine effects were centrally mediated. These data implicate muscarinic receptors in the central nervous system in the control of executive function. Taken together with other recent data, they may also suggest an important role for cholinergic receptors outside of the neocortex in regulating these aspects of attention and executive function.
中枢神经系统中胆碱能神经元受损会导致注意力和执行功能多个方面出现障碍。情感和注意力转换是执行功能的两个方面，由前额叶皮层的不同区域控制。胆碱能神经机制在这些执行功能方面的作用尚未明确。为了确定中枢毒蕈碱胆碱能受体是否参与情感和/或注意力转换，我们在毒蕈碱拮抗剂东莨菪碱的全身影响下，对大鼠进行了一系列辨别学习问题测试，其中包括情感（反转学习）和注意力转换（维度外转换）成分。东莨菪碱损害了反转学习和维度外转换，但对不需要情感或注意力转换的新辨别问题的学习没有影响。不能穿过血脑屏障的甲基东莨菪碱的全身给药并未损害情感或注意力转换，这表明东莨菪碱的作用是由中枢介导的。这些数据表明中枢神经系统中的毒蕈碱受体参与执行功能的控制。与其他近期数据一起，它们还可能表明新皮层以外的胆碱能受体在调节注意力和执行功能的这些方面起着重要作用。
