神经递质检测方法的研究进展  

Recent Advances in Detection Methods for Neurotransmitters

作　　者：万金霞 李毓龙 WAN Jin-Xia;LI Yu-Long(State Key Laboratory of Membrane Biology,School of Life Sciences,Peking University,Beijing 100871,China;PKU-IDG/McGovern Institute for Brain Research,Peking University,Beijing 100871,China;Peking-Tsinghua Center for Life Sciences,Beijing 100871,China;Chinese Institute for Brain Research,Beijing 100871,China)

机构地区：[1]北京大学生命科学学院膜生物学国家重点实验室,北京100871 [2]北京大学麦戈文脑科学研究所,北京100871 [3]北大-清华生命科学联合中心,北京100871 [4]北京脑科学与类脑研究中心,北京100871

出　　处：《分析化学》2020年第3期307-315,共9页Chinese Journal of Analytical Chemistry

基　　金：北京市科委生命科学前沿创新培育项目(No.Z181100001318002);国家重点基础研究发展规划(973计划)项目(No.2015CB856402);国家自然科学基金项目(Nos.31671118,31371442)资助~~

摘　　要：人的大脑中存在数以亿计的神经元,而神经元之间的信息传递主要依赖于通过化学突触发挥作用的神经递质。精确研究神经递质的动态变化对于理解神经系统的功能和研究神经系统疾病的发病机理等均具有重要意义。本文从技术原理、应用以及局限性等方面总结了近年来发展的一系列检测神经递质的方法,着重介绍了基于G蛋白偶联受体(G protein coupled receptor,GPCR)激活原理构建的可遗传编码荧光探针,此系列探针在特异性、灵敏度及时空分辨率方面均有优异的表现,同时,在活体动物实验中也表现出良好的信噪比。此外,此类探针的构建原理具有普适性,可用于开发检测不同神经递质的荧光探针。The human brain consists of billions of neurons,and the communication between neurons mainly relies on various neurotransmitters which are released at chemical synapses.Therefore,it is important to monitor neurotransmitter release with high temporal and spatial resolution to understand the functions of nervous system and in turn provide insights into psychiatric disease mechanisms.In this review,we summarize different categories of methods for monitoring neurotransmitters dynamics developed in recent decades in terms of principles,applications and limitations.We focus on the G protein-coupled receptor(GPCR)activation Based sensors,GRAB,which shows high temporal-spatial resolution,high sensitivity and high molecular specificity.GRAB sensors also perform well in multiple organisms,including zebrafish,drosophila and mice.In addition,the principle of GRAB sensors can be applied in general to develop sensors for detecting different neurotransmitters whose receptors share the conserved conformational changes when activated by corresponding ligands.In summary,these tools are useful for deciphering the dynamic regulation of a plethora of neurotransmitters in various neural circuits,and may enhance the understanding of the complex neuromodulation in both physiological and pathological processes.

关 键 词：神经递质 荧光成像 G蛋白偶联受体 评述 

分 类 号：O657.3[理学—分析化学] R446.1[理学—化学]