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科学家开发出可用于监测体内多巴胺能活性的下一代GRAB传感器
作者:小柯机器人 发布时间:2020/10/25 22:08:53

北京大学李毓龙等研究人员合作开发出可用于监测体内多巴胺能活性的下一代GRAB传感器。该研究于2020年10月21日在线发表于国际一流学术期刊《自然—方法学》。

研究人员开发了基于红色荧光G蛋白偶联受体激活的多巴胺(DA)传感器(GRABDA)以及绿色荧光GRABDA传感器的优化版本。响应于细胞外DA,红色和绿色GRABDA传感器均显示出荧光的大幅增加,具有亚细胞分辨率、亚秒动力学和纳摩尔至亚微摩尔亲和力。
 
此外,GRABDA传感器可解析小鼠脑片中诱发的DA释放,检测活果蝇中单个神经元诱发的隔室DA释放,并报告光遗传学引起的黑纹状体DA释放以及在行为自由小鼠的性行为期间多巴胺能活性。与绿色GRABDA或钙指示剂GCaMP6s共表达红色GRABDA可以跟踪体内不同回路中的多巴胺能信号传导和神经元活性。
 
据介绍,DA在大脑中起着至关重要的作用,并且直接测量多巴胺能活动对于了解其生理功能至关重要。
 
附:英文原文

Title: Next-generation GRAB sensors for monitoring dopaminergic activity in vivo

Author: Fangmiao Sun, Jingheng Zhou, Bing Dai, Tongrui Qian, Jianzhi Zeng, Xuelin Li, Yizhou Zhuo, Yajun Zhang, Yipan Wang, Cheng Qian, Ke Tan, Jiesi Feng, Hui Dong, Dayu Lin, Guohong Cui, Yulong Li

Issue&Volume: 2020-10-21

Abstract: Dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed red fluorescent G-protein-coupled receptor-activation-based DA (GRABDA) sensors and optimized versions of green fluorescent GRABDA sensors. In response to extracellular DA, both the red and green GRABDA sensors exhibit a large increase in fluorescence, with subcellular resolution, subsecond kinetics and nanomolar-to-submicromolar affinity. Moreover, the GRABDA sensors resolve evoked DA release in mouse brain slices, detect evoked compartmental DA release from a single neuron in live flies and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Coexpressing red GRABDA with either green GRABDA or the calcium indicator GCaMP6s allows tracking of dopaminergic signaling and neuronal activity in distinct circuits in vivo. Red and improved green versions of the genetically encoded dopamine sensor GRABDA have been developed. These neurotransmitter sensors are used alone or in combination with, for example, calcium sensors in behaving fruit flies and rodents.

DOI: 10.1038/s41592-020-00981-9

Source: https://www.nature.com/articles/s41592-020-00981-9

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex