2024年3月5日，北京大学李毓龙研究团队在《自然—方法学》杂志发表论文，开发出用于监测体内时空血清素释放的改进型绿色和红色GRAB传感器。

研究人员表示，血清素能系统在生理和病理过程中都发挥着重要作用，也是许多精神疾病的治疗靶点。虽然最近开发出了几种基于基因编码GFP的血清素（5-HT）传感器，但它们的灵敏度和光谱谱相对有限。

为了克服这些局限性，研究人员优化了基于绿色荧光G蛋白偶联受体（GPCR）激活的5-HT （GRAB_5-HT）传感器，并开发了红色荧光GRAB_5-HT传感器。这些传感器具有良好的细胞表面迁移性、高特异性、高灵敏度和高时空分辨率，因此适用于体内5-HT动态监测。除了记录自由移动小鼠皮层下的5-HT释放外，研究人员还通过中观成像观察了小鼠背侧皮层中均匀和梯度的5-HT释放。

最后，研究人员进行了双色成像，在钙波和内源性大麻素波之后，观察到癫痫发作诱发的整个皮层的5-HT释放波。总之，这些5-HT传感器能为人们提供有关健康和疾病中血清素能系统的宝贵信息。

附：英文原文

Title: Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo

Author: Deng, Fei, Wan, Jinxia, Li, Guochuan, Dong, Hui, Xia, Xiju, Wang, Yipan, Li, Xuelin, Zhuang, Chaowei, Zheng, Yu, Liu, Laixin, Yan, Yuqi, Feng, Jiesi, Zhao, Yulin, Xie, Hao, Li, Yulong

Issue&Volume: 2024-03-05

Abstract: The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensors and developed a red fluorescent GRAB5-HT sensor. These sensors exhibit excellent cell surface trafficking and high specificity, sensitivity and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both health and disease.

DOI: 10.1038/s41592-024-02188-8

Source: https://www.nature.com/articles/s41592-024-02188-8