Department of Medical Neurobiology, Hadassah Medical school - Hebrew University, Jerusalem, Israel.
Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
J Neurochem. 2021 Sep;158(6):1274-1291. doi: 10.1111/jnc.15164. Epub 2020 Sep 25.
Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground-breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine-mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine-activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in-depth current knowledge on acetylcholine-activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.
乙酰胆碱是所有动物中丰富的神经递质。乙酰胆碱的作用取决于受体和细胞类型，表现为兴奋、抑制或调节作用。利用线虫 C. elegans 进行的研究，对胆碱能传递的机制理解做出了突破性的贡献。针对行为突变体或对药理学试剂反应的强大遗传筛选，确定了突触传递的核心细胞机制。扰乱乙酰胆碱介导过程的药理学试剂导致了发现，也揭示了乙酰胆碱激活通道和受体的组成和调节剂。通过电生理学和分子细胞研究的结合，我们在突触、神经回路和动物行为水平上对胆碱能信号有了深刻的理解。这篇综述将从历史概述开始，然后深入介绍当前关于乙酰胆碱激活的离子型受体的知识，包括调节它们功能表达的机制及其在调节运动中的作用。
