An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning  

作　　者：Mingyue Lv Ruyi Cai Renzimo Zhang Xiju Xia Xuelin Li Yipan Wang Huan Wang Jianzhi Zeng Yifei Xue Lanqun Mao Yulong Li 

机构地区：[1]State Key Laboratory of Membrane Biology,School of Life Sciences,Peking University,Beijing 100871,China [2]State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [3]PKU-IDG/McGovern Institute for Brain Research,Beijing 100871,China [4]Yuanpei College,Peking University,Beijing 100871,China [5]Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China [6]Peking University–Tsinghua University–National Institute of Biological Sciences Joint Graduate Program,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China [7]Institute of Molecular Physiology,Shenzhen Bay Laboratory,Shenzhen 518107,China [8]College of Chemistry,Beijing Normal University,Beijing 100875,China [9]Chinese Institute for Brain Research,Beijing 102206,China

出　　处：《National Science Review》2024年第5期179-194,共16页国家科学评论（英文版）

基　　金：supported by grants to Yulong Li from the National Key R&DProgram of China(2019YFE011781);the National Natural Science Foundation of China(31925017 and 31871087);the NIH BRAIN Initiative(1U01NS113358 and 1U01NS120824);the Feng Foundation of Biomedical Research,the Clement and Xinxin Foundation,the Peking-TsinghuaCenter for Life Sciences,the State Key Laboratory of Membrane Biology at Peking University School of Life Sciences and the New Cornerstone Science Foundation through the New Cornerstone Investigator Program and the XPLORER PRIZE.

摘　　要：Octopamine(OA),analogous to norepinephrine in vertebrates,is an essentialmonoamine neurotransmitter in invertebrates that plays a significant role in various biological functions,including olfactory associative learning.However,the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect it.To overcome these limitations,we developed a genetically encoded GPCR activation-based(GRAB)OA sensor called GRABOA1.0.This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA.Using GRABOA1.0,we monitored OA release in the Drosophila mushroom body(MB),the fly’s learning center,and found that OA is released in response to both odor and shock stimuli in an aversive learning model.This OA release requires acetylcholine(ACh)released from Kenyon cells,signaling via nicotinic ACh receptors.Finally,we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octβ1R in dopaminergic neurons,leading to alterations in synaptic plasticity within theMB.Thus,our new GRABOA1.0 sensor can be used to monitor OA release in real time under physiological conditions,providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

关 键 词：OCTOPAMINE DOPAMINE GRAB sensor learning and memory 

分 类 号：TN32[电子电信—物理电子学]