Detection of neuropeptides in vivo and open questions for current and upcoming fluorescent sensors for neuropeptides.

During a stress response, various neuropeptides are secreted in a spatiotemporally coordinated way in the brain. For a precise understanding of peptide functions in a stress response, it is important to investigate when and where they are released, how they diffuse, and how they are broken down in the brain. In the past two decades, genetically encoded fluorescent calcium indicators have greatly advanced our knowledge of the functions of specific neuronal activity in regulation of behavioral changes and physiological responses during stress. In addition, various kinds of structural information on G-protein-coupled receptors (GPCRs) for neuropeptides have been revealed. Recently, genetically encoded fluorescent sensors have been developed for detection of neurotransmitters by making use of conformational changes induced by ligand binding. In this review, we summarize the recent and upcoming advances of techniques for detection of neuropeptides and then present several open questions that will be solved by application of recent or upcoming technical advances in detection of neuropeptides in vivo.