Graduate Program in Biochemistry, Molecular, Cellular, and Developmental Biology, University of California, Davis, California, USA.
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California, USA; email:
Annu Rev Neurosci. 2022 Jul 8;45:273-294. doi: 10.1146/annurev-neuro-110520-031137. Epub 2022 Mar 22.
Recent advances in fluorescence imaging permit large-scale recording of neural activity and dynamics of neurochemical release with unprecedented resolution in behaving animals. Calcium imaging with highly optimized genetically encoded indicators provides a mesoscopic view of neural activity from genetically defined populations at cellular and subcellular resolutions. Rigorously improved voltage sensors and microscopy allow for robust spike imaging of populational neurons in various brain regions. In addition, recent protein engineering efforts in the past few years have led to the development of sensors for neurotransmitters and neuromodulators. Here, we discuss the development and applications of these genetically encoded fluorescent indicators in reporting neural activity in response to various behaviors in different biological systems as well as in drug discovery. We also report a simple model to guide sensor selection and optimization.
近年来，荧光成像技术的进步使得在行为动物中以前所未有的分辨率大规模记录神经活动和神经化学释放动力学成为可能。经过高度优化的遗传编码指示剂的钙成像提供了细胞和亚细胞分辨率下遗传定义群体的神经活动的介观视图。经过严格改进的电压传感器和显微镜允许对各种脑区的群体神经元进行稳健的尖峰成像。此外，在过去几年中，蛋白质工程方面的努力导致了用于神经递质和神经调质的传感器的开发。在这里，我们讨论了这些遗传编码荧光指示剂在不同生物系统中响应各种行为报告神经活动以及在药物发现中的开发和应用。我们还报告了一个简单的模型来指导传感器的选择和优化。
