A fluorescent sensor for the real-time measurement of extracellular oxytocin dynamics in the brain

A fluorescent sensor for the real-time measurement of extracellular oxytocin dynamics in the brain
复制标题

用于实时测量大脑细胞外催产素动态的荧光传感器

DOI:
10.1101/2021.07.30.454450
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发表时间:
2021
期刊:
bioRxiv
影响因子:
--
通讯作者:
Nishiyama Masaaki
Nishiyama Masaaki
中科院分区:
--
文献类型:
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作者:
Ino Daisuke;Hibino Hiroshi;Nishiyama Masaaki

文献摘要

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催产素(OT)是一种下丘脑神经肽,在大脑中起神经调节剂的作用,协调各种动物行为。然而,大脑OT动力学和复杂动物行为之间的关系在很大程度上仍然难以捉摸,部分原因是缺乏一种合适的技术来实时记录其在体内的活动。在这里,我们描述了MTRIAOT,一种基于g蛋白偶联受体的绿色荧光OT传感器,具有大的动态范围,合适的亲和力,对OT同源物的配体特异性,对下游信号传导的影响最小和长期荧光稳定性。通过结合病毒基因传递和纤维光度法介导的荧光测量,我们证明了mtriaot在活体小鼠脑OT动态实时检测中的实用性。mtriaot介导的测量表明,OT动力学的可变性取决于动物的行为背景和身体状况。mtriaot将有可能分析各种生理和病理过程中的OT动力学。
Oxytocin (OT), a hypothalamic neuropeptide that acts as a neuromodulator in the brain, orchestrates a variety of animal behaviors. However, the relationship between brain OT dynamics and complex animal behaviors remains largely elusive, partly because of the lack of a suitable technique for its real-time recording in vivo. Here, we describe MTRIAOT, a G-protein-coupled receptor-based green fluorescent OT sensor that has a large dynamic range, suitable affinity, ligand specificity for OT orthologs, minimal effects on downstream signaling and long-term fluorescence stability. By combining viral gene delivery and fiber photometry-mediated fluorescence measurements, we demonstrate the utility of MTRIAOTfor real-time detection of brain OT dynamics in living mice. MTRIAOT-mediated measurements indicate variability of OT dynamics depending on the behavioral context and physical condition of an animal. MTRIAOTwill likely enable the analysis of OT dynamics in a variety of physiological and pathological processes.