癫痫是一种慢性中枢神经系统疾病,其发生不仅与“兴奋性谷氨酸能神经元和抑制性γ-氨基丁酸(γ-GABA)能神经元的失衡”相关,亦与异常的中枢胆碱能神经元调控有着密切联系。本文从细胞分子水平和神经网络水平概括了癫痫发作过程中中枢胆碱能系统的结构功能改变及其在癫痫中可能扮演的角色。在细胞分子水平,多个不同脑区的代谢型毒蕈碱样胆碱能受体异常与多种类型癫痫密切相关,而离子型烟碱样受体突变与一种特定癫痫类型常染色体显性引发的额叶癫痫相关。在神经网络水平,脑内投射型胆碱能神经元及其与其他神经元的交互作用可能参与癫痫发作,尤其基底前脑到海马的胆碱能神经元投射可能与癫痫密切相关,而局部中间型胆碱能神经元暂未发现与癫痫有关。随着光遗传学等技术的发展,发现并解析胆碱能相关的癫痫环路机制并进行调控已成为目前研究的热点。
Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-antosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.