Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
Int J Mol Sci. 2020 Oct 28;21(21):8048. doi: 10.3390/ijms21218048.
Understanding how dopamine (DA) encodes behavior depends on technologies that can reliably monitor DA release in freely-behaving animals. Recently, red and green genetically encoded sensors for DA (dLight, GRAB-DA) were developed and now provide the ability to track release dynamics at a subsecond resolution, with submicromolar affinity and high molecular specificity. Combined with rapid developments in in vivo imaging, these sensors have the potential to transform the field of DA sensing and DA-based drug discovery. When implementing these tools in the laboratory, it is important to consider there is not a 'one-size-fits-all' sensor. Sensor properties, most importantly their affinity and dynamic range, must be carefully chosen to match local DA levels. Molecular specificity, sensor kinetics, spectral properties, brightness, sensor scaffold and pharmacology can further influence sensor choice depending on the experimental question. In this review, we use DA as an example; we briefly summarize old and new techniques to monitor DA release, including DA biosensors. We then outline a map of DA heterogeneity across the brain and provide a guide for optimal sensor choice and implementation based on local DA levels and other experimental parameters. Altogether this review should act as a tool to guide DA sensor choice for end-users.
了解多巴胺 (DA) 如何编码行为取决于能够可靠地监测自由行为动物中 DA 释放的技术。最近，开发了用于 DA 的红色和绿色基因编码传感器 (dLight、GRAB-DA)，现在能够以亚秒分辨率、亚微摩尔亲和力和高分子特异性跟踪释放动力学。结合体内成像的快速发展，这些传感器有可能改变 DA 感应和基于 DA 的药物发现领域。在实验室中实施这些工具时，重要的是要考虑没有“一刀切”的传感器。传感器特性，最重要的是它们的亲和力和动态范围，必须仔细选择以匹配局部 DA 水平。分子特异性、传感器动力学、光谱特性、亮度、传感器支架和药理学根据实验问题进一步影响传感器的选择。在这篇综述中，我们以 DA 为例；我们简要总结了监测 DA 释放的旧技术和新技术，包括 DA 生物传感器。然后，我们概述了大脑中 DA 异质性的图谱，并根据局部 DA 水平和其他实验参数为最佳传感器选择和实施提供了指南。总的来说，这篇综述应该作为一个工具，为最终用户指导 DA 传感器的选择。
