G-protein-coupled receptor-based sensors for imaging neurochemicals with high sensitivity and specificity

Neurotransmitters and neuromodulators are key neurochemicals that mediate cell-cell communication, maintain the body's homeostasis, and control a wide range of biological processes. Thus, dysregulation of neurochemical signaling is associated with a range of psychiatric disorders and neurological diseases. Understanding the physiological and pathophysiological functions of neurochemicals, particularly in complex biological systems in vivo, requires tools that can probe their dynamics with high sensitivity and specificity. Recently, genetically encoded fluorescent sensors for visualizing specific neurochemicals were developed by coupling neurochemical-sensing G-protein-coupled receptors (GPCRs) with a circular-permutated fluorescent protein. These GPCR-based sensors can monitor the dynamics of neurochemicals in behaving animals with high spatiotemporal resolution. Here, we review recent progress regarding the development and application of GPCR-based sensors for imaging neurochemicals, and we discuss future perspectives.