Department of Physiology and Pharmacology, The University of Western Ontario, London, ON, Canada.
Robarts Research Institute, The University of Western Ontario, London, ON, Canada.
Front Neural Circuits. 2021 Mar 15;15:648624. doi: 10.3389/fncir.2021.648624. eCollection 2021.
Neuromodulation by acetylcholine plays a vital role in shaping the physiology and functions of cerebral cortex. Cholinergic neuromodulation influences brain-state transitions, controls the gating of cortical sensory stimulus responses, and has been shown to influence the generation and maintenance of persistent activity in prefrontal cortex. Here we review our current understanding of the role of muscarinic cholinergic receptors in primate prefrontal cortex during its engagement in the performance of working memory tasks. We summarize the localization of muscarinic receptors in prefrontal cortex, review the effects of muscarinic neuromodulation on arousal, working memory and cognitive control tasks, and describe the effects of muscarinic M1 receptor stimulation and blockade on the generation and maintenance of persistent activity of prefrontal neurons encoding working memory representations. Recent studies describing the pharmacological effects of M1 receptors on prefrontal persistent activity demonstrate the heterogeneity of muscarinic actions and delineate unexpected modulatory effects discovered in primate prefrontal cortex when compared with studies in rodents. Understanding the underlying mechanisms by which muscarinic receptors regulate prefrontal cognitive control circuitry will inform the search of muscarinic-based therapeutic targets in the treatment of neuropsychiatric disorders.
乙酰胆碱的神经调节在塑造大脑皮层的生理学和功能方面起着至关重要的作用。胆碱能神经调节影响脑状态的转变，控制皮质感觉刺激反应的门控，并已被证明影响前额叶皮层中持续活动的产生和维持。在这里，我们回顾了我们目前对在执行工作记忆任务时灵长类动物前额叶皮层中烟碱型乙酰胆碱受体作用的理解。我们总结了烟碱型乙酰胆碱受体在前额皮质中的定位，综述了烟碱型乙酰胆碱能调制对觉醒、工作记忆和认知控制任务的影响，并描述了烟碱型乙酰胆碱 M1 受体刺激和阻断对编码工作记忆表现的前额叶神经元持续活动的产生和维持的影响。最近描述 M1 受体对前额叶持续活动的药理学作用的研究表明，烟碱型乙酰胆碱能作用具有异质性，并且当与啮齿动物研究相比时，在前额叶皮层中发现了意想不到的调节作用。了解烟碱型乙酰胆碱受体调节前额叶认知控制回路的潜在机制将为寻找基于烟碱型乙酰胆碱受体的治疗靶点治疗神经精神疾病提供信息。
