Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli.

荧光传感器是生命科学实验工具箱中必不可少的部分，广泛用于可视化细胞内和细胞外信号。在大脑中，光学神经递质传感器可以通过直接观察（例如）神经递质的释放和扩散来阐明信号传输的时间和空间方面。在这里，我们报告了氨基酸甘氨酸的第一个光学传感器的开发和应用，该氨基酸既是抑制性神经递质又是N-甲基-d的共激动剂。-天冬氨酸受体（NMDARs）参与突触可塑性。甘氨酸特异性结合蛋白的计算设计使我们能够生产光学甘氨酸FRET传感器（GlyFS），该传感器可与单光子和双光子激发荧光显微镜一起使用。我们利用这种新开发的传感器来测试关于胞外空间中甘氨酸空间分布不均匀的预测，并证明胞外甘氨酸水平受可塑性诱导刺激的控制。