College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education , Peking University , Beijing 100871 , China.
Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research , Peking University , Beijing 100871 , China.
ACS Chem Neurosci. 2018 Apr 18;9(4):639-650. doi: 10.1021/acschemneuro.7b00455. Epub 2018 Mar 9.
Optical biosensors have been invaluable tools in neuroscience research, as they provide the ability to directly visualize neural activity in real time, with high specificity, and with exceptional spatial and temporal resolution. Notably, a majority of these sensors are based on fluorescent protein scaffolds, which offer the ability to target specific cell types or even subcellular compartments. However, fluorescent proteins are intrinsically bulky tags, often insensitive to the environment, and always require excitation light illumination. To address these limitations, there has been a proliferation of alternative sensor scaffolds developed in recent years, including hybrid sensors that combine the advantages of synthetic fluorophores and genetically encoded protein tags, as well as bioluminescent probes. While still in their early stage of development as compared with fluorescent protein-based sensors, these novel probes have offered complementary solutions to interrogate various aspects of neuronal communication, including transmitter release, changes in membrane potential, and the production of second messengers. In this Review, we discuss these important new developments with a particular focus on design strategies.
光学生物传感器在神经科学研究中是非常有价值的工具，因为它们能够实时提供高特异性、出色时空分辨率的直接可视化神经活动的能力。值得注意的是，这些传感器中的大多数都是基于荧光蛋白支架，它能够靶向特定的细胞类型甚至亚细胞区室。然而，荧光蛋白本质上是体积庞大的标签，通常对环境不敏感，并且始终需要激发光照明。为了解决这些限制，近年来已经开发出了大量替代传感器支架，包括结合了合成荧光团和遗传编码蛋白标签的混合传感器，以及生物发光探针。与基于荧光蛋白的传感器相比，虽然这些新型探针还处于早期开发阶段，但它们提供了互补的解决方案，可以检测神经元通讯的各个方面，包括递质释放、膜电位变化和第二信使的产生。在这篇综述中，我们讨论了这些重要的新进展，特别关注设计策略。
