Real-time measurement of neuromodulators using GRAB sensors

Abstract

To advance our understanding of the neuronal mechanisms underpinning animal behavior, it is important to integrate traditional electrophysiological methodologies with cutting-edge technologies capable of providing detailed insights into the dynamics of neuromodulators. However, achievement of high spatial and temporal resolution in neuromodulator measurements has presented significant challenges, particularly in the context of real-time observations within freely behaving animals. Recent innovations, exemplified by the development of genetically encoded fluorescent indicator, commonly referred to as “GRAB sensors,” have addressed these limitations. These tools enable the real-time, high-precision quantification of neuromodulators, representing a transformative advancement in the field. Notably, GRAB sensors have been designed to target a broad spectrum of neuromodulators, including dopamine (DA), acetylcholine (ACh), noradrenaline/norepinephrine (NE), and neuropeptides, offering unparalleled specificity, sensitivity, and temporal resolution. This review provides an overview of the features and advantages of GRAB sensors, highlights their diverse applications, and discusses key considerations pertinent to their implementation in contemporary neuroscience research.