特异性控制神经元活性法研究睡眠-觉醒机制新进展  

Recent Advance on Sleep-Wake Regulation Based on Novel Techniques for Specific Manipulations of Neuron Activities

作　　者：杨燕飞 黄志力 YANG Yan-fei;HUANG Zhi-li(Department of Pharmacology, School of Basic Medical Science;State Key Laboratory of Medical Neurobiolog;Institutes of Brain Science and Collaborative Innovation Center for Brain Sciences, Fudan University, Shanghai,200032, China)

机构地区：[1]复旦大学基础医学院药理学系医学神经生物学国家重点实验室脑科学研究院与脑科学协同创新中心

出　　处：《神经药理学报》2018年第1期23-34,共12页Acta Neuropharmacologica

基　　金：国家自然科学基金项目(No.81420108015;31530035;31671099;31471064;31571103;31421091);国家重点基础研究发展计划973基金项目(No.2015CB856401);上海市科委基金项目(No.14JC1400900)

摘　　要：人生的三分之一在睡眠中度过,但人为什么要睡眠,睡眠-觉醒如何调控,至今仍是未解之谜。利用电生理、药理学、免疫组织化学和神经元损毁等传统研究手段,发现脑内调控睡眠的核团主要有下丘脑腹外侧视前区和面神经旁核等;觉醒调控核团主要有中缝背核、蓝斑核、结节乳头核、外侧下丘脑和基底前脑等。这些调控睡眠和觉醒的核团相互制约,维持机体正常的睡眠觉醒周期。但是,由于传统研究方法不能对神经元活性进行特异性操纵,限制了人们认识新型睡眠觉醒调控核团。近年来,随着特异性操纵神经元活性技术的开发和应用,研究者们可以精确地控制不同脑区各类型神经元的活性,包括γ-氨基丁酸能、谷氨酸能和胆碱能神经元等,研究其在睡眠-觉醒调控中扮演的角色,或发现更多的调控核团。该文重点综述基于光遗传学和化学遗传学技术研究睡眠-觉醒调控机制的新进展。One-third of life is spent in sleep,but why we need to sleep and how sleep-wake cycles regulate are still mysterious. The previous used pharmacology,immunohistochemistry,neuronal damage and other traditional research methods have partly revealed several brain areas related to sleep-wake. As it familiar to us that hypothalamic ventrolateral preoptic area and parafacial zone are sleep-promoting areas,while the midbrain dorsal raphe,locus coeruleus,tuberomammillary nucleus,lateral hypothalamus and basal forebrain wake-promoting areas. Though these brain regions that regulate sleep-wake are interacting,they also closely linked to maintain normal sleep-wake cycles. However,due to the poor spatial specificity and selectivity by traditional technology,it is tough to accurately explore more new sleep-wake related brain areas and neurons. In recent years,with the application of specific manipulation of neuron activity,researchers can specifically control different kinds of neuronal activities in the brain,including GABAergic,glutamatergic,and cholinergic neurons to study their roles in sleep-wake regulations,or to identify new brain regions. This review focuses on the new progress in the study of sleep-wake regulation mechanism based on optogenetic and chemogenetic techniques.

关 键 词：化学遗传学 Cre-小鼠 光遗传学 睡眠-觉醒周期 

分 类 号：R964[医药卫生—药理学]