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

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

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Octopamine(OA),analogous to norepinephrine in vertebrates,is an essential monoamine 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 the MB.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.

octopaminedopamineGRAB sensorlearning and memory

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

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State Key Laboratory of Membrane Biology,School of Life Sciences,Peking University,Beijing 100871,China

State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

PKU-IDG/McGovern Institute for Brain Research,Beijing 100871,China

Yuanpei College,Peking University,Beijing 100871,China

Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

Institute of Molecular Physiology,Shenzhen Bay Laboratory,Shenzhen 518107,China

College of Chemistry,Beijing Normal University,Beijing 100875,China

Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program,Academy for Advanced Interdisciplinary Studies,Peking Un

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国家重点研发计划国家自然科学基金国家自然科学基金NIH BRAIN InitiativeNIH BRAIN InitiativeFeng Foundation of Biomedical ResearchClement and Xinxin FoundationPeking-Tsinghua Center for Life SciencesState Key Laboratory of Membrane Biology at Peking University School of Life SciencesNew Cornerstone Science Foundation through the New Cornerstone Investigator ProgramXPLORER Prize

2019YFE01178131925017318710871U01NS1133581U01NS120824

2024

10.1093/nsr/nwae112

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ISSN：
年,卷(期)：2024.11(5)
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