小柯机器人

科学家开发出更灵敏的乙酰胆碱探针
2020-09-30 15:55

北京大学李毓龙、井淼等研究人员合作开发出一种优化的乙酰胆碱传感器,可监测体内胆碱能活动。2020年9月28日,《自然—方法学》在线发表了这项成果。

研究人员优化了GRABACh(基于GPCR激活)传感器,以大幅提高乙酰胆碱(ACh)检测的灵敏度,并减少了下游与细胞内途径的偶联。ACh传感器的改进版本保留了其前身ACh的亚秒级响应动力学、生理相关的亲和力和精确的分子特异性。使用此传感器,研究人员揭示出响应外部刺激(包括气味和身体休克)的转基因果蝇嗅觉中心隔室ACh信号。
 
通过使用光纤光度记录和双光子成像,这一ACh传感器还能够对执行多种行为小鼠的多个大脑区域的单次ACh动态进行灵敏检测。
 
据悉,直接测量ACh释放的能力是了解其生理功能的重要步骤。
 
附:英文原文

Title: An optimized acetylcholine sensor for monitoring in vivo cholinergic activity

Author: Miao Jing, Yuexuan Li, Jianzhi Zeng, Pengcheng Huang, Miguel Skirzewski, Ornela Kljakic, Wanling Peng, Tongrui Qian, Ke Tan, Jing Zou, Simon Trinh, Runlong Wu, Shichen Zhang, Sunlei Pan, Samuel A. Hires, Min Xu, Haohong Li, Lisa M. Saksida, Vania F. Prado, Timothy J. Bussey, Marco A. M. Prado, Liangyi Chen, Heping Cheng, Yulong Li

Issue&Volume: 2020-09-28

Abstract: The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRABACh (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors. A genetically encoded acetylcholine sensor with improved sensitivity allows detection of cholinergic neurotransmission in vivo in the Drosophila and mouse brain.

DOI: 10.1038/s41592-020-0953-2

Source: https://www.nature.com/articles/s41592-020-0953-2

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:47.99
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex


本期文章:《自然—方法学》:Online/在线发表

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