Laboratory of Neuropsychology, NIMH, Bethesda, MD 20892, USA.
Neurobiol Learn Mem. 2012 Jul;98(1):41-6. doi: 10.1016/j.nlm.2012.04.007. Epub 2012 Apr 26.
Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells.
将非选择性毒蕈碱拮抗剂东莨菪碱的微量输注到边缘区皮质会损害视觉识别任务的表现,表明该区域的毒蕈碱受体在识别记忆中起着关键作用。为了评估在边缘区皮质中选择性阻断毒蕈碱受体亚型的记忆效应,我们在进行单次视觉识别的动物中局部输注 m1 选择性拮抗剂哌仑西平和 m2 选择性拮抗剂甲硫哒嗪,并将这些分数与接受等量生理盐水输注的分数进行比较。与这些对照输注相比,哌仑西平注射而不是甲硫哒嗪注射显著损害了识别准确性。此外,类似剂量的东莨菪碱和哌仑西平产生了类似的缺陷,表明先前用东莨菪碱获得的缺陷主要(如果不是完全)是由于 m1 受体的阻断。本研究结果表明,m1 和 m2 受体具有功能上可分离的作用,并且新的视觉记忆的形成严重依赖于位于边缘区细胞上的 m1 受体的胆碱能激活。