美国加州大学Lin Tian，Matthew R. Banghart和美国华盛顿大学Michael R. Bruchas共同合作，近期取得重要工作进展。他们研究提出，科学家利用基因编码生物传感器揭示阿片类神经肽的动态变化。相关研究成果2024年7月15日在线发表于《自然—神经科学》杂志上。

据介绍，神经肽在神经系统中无处不在。神经肽的研究一直受到缺乏实验工具的限制，无法以电路特定的方式精确剖析其复杂多样的动力学。阿片肽调节疼痛、奖励和厌恶，因此具有很高的临床相关性。

为了阐明大脑内源性阿片样物质信号传导的时空动态，研究人员开发了一类基于kappa, delta和mu阿片样受体的基因编码荧光传感器：κLight、δLight和µLight。研究人员描述了这些传感器在哺乳动物细胞和分离神经元中的药理学特征。研究人员使用κLight来识别触发内源性阿片类药物释放的电刺激参数以及脑切片中强啡肽体积传输的时空尺度。

通过在小鼠体内使用纤维光度法，研究人员证明了这些传感器在检测光遗传学驱动的阿片类药物释放方面的实用性，并观察了不同阿片类物质对恐惧和奖励条件反应的释放动力学。

附：英文原文

Title: Unlocking opioid neuropeptide dynamics with genetically encoded biosensors

Author: Dong, Chunyang, Gowrishankar, Raajaram, Jin, Yihan, He, Xinyi Jenny, Gupta, Achla, Wang, Huikun, Sayar-Atasoy, Nilfer, Flores, Rodolfo J., Mahe, Karan, Tjahjono, Nikki, Liang, Ruqiang, Marley, Aaron, Or Mizuno, Grace, Lo, Darren K., Sun, Qingtao, Whistler, Jennifer L., Li, Bo, Gomes, Ivone, Von Zastrow, Mark, Tejeda, Hugo A., Atasoy, Deniz, Devi, Lakshmi A., Bruchas, Michael R., Banghart, Matthew R., Tian, Lin

Issue&Volume: 2024-07-15

Abstract: Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and μLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

DOI: 10.1038/s41593-024-01697-1

Source: https://www.nature.com/articles/s41593-024-01697-1