New biosensors have helped reveal the activity of neuropeptides in the brain, researchers report, providing novel tools for studying the release, function, and regulation of these crucial signaling molecules in vivo. According to the study, the approach has the potential to address key questions regarding neuropeptides and their roles in health and disease.

In the brain, neuropeptides are key signaling molecules in the body that regulate many critical physiological functions, including digestion, metabolism, sleep, and higher cognitive processes. Because of this, neuropeptide signaling, which is primarily mediated by G protein-coupled receptors (GPCRs), provides a key site for drug targeting for a wide range of diseases and conditions such as obesity, diabetes, insomnia, and chronic pain.

Although the ability to measure the spatial and temporal dynamics of neuropeptides in vivo is essential for understanding their functions and the mechanisms underlying their regulation, current tools for detecting these molecules in the brain and monitoring their effects are lacking. As a result, the precise spatiotemporal dynamics and release patterns of neuropeptides in the brain remain poorly understood.

Here, the researchers present a generalized method for engineering genetically encoded fluorescent neuropeptide biosensors. They developed and characterized a series of highly selective and sensitive GPCR activation-based sensors (GRABs) for detecting several neuropeptides, including somatostatin (SST), corticotropin-releasing factor (CRF), cholecystokinin (CCK), neuropeptide Y (NPY), neurotensin (NTS), and vasoactive intestinal peptide (VIP).

In in vitro and in vivo experiments in cultured cells and mice, the authors showed that the GRABs were highly sensitive and could detect specific neuropeptide release with a high spatiotemporal resolution without affecting signaling pathways.

According to the authors their approach could be used to design a GRAB sensor for almost any neuropeptide and study organism-wide neuropeptide signaling.

https://www.science.org/doi/10.1126/science.abq8173