A new sensor toolkit for studying neuropeptides

A new sensor toolkit for studying neuropeptides

Subject: Science and Tech

Section: Biotech

Context

• 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 signalling molecules in vivo.
• According to a study, the approach has the potential to address questions  regarding neuropeptides and their roles in health and disease.

About Neuropeptides and Their Detection 

• Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes, including energy balance, sleep and circadian rhythms, stress, and social behaviors. Understanding the functions of neuropeptides in vivo requires the ability to monitor their dynamics with high specificity, sensitivity, and spatiotemporal resolution; however, this has been hindered by the lack of direct, sensitive and non-invasive tools.
• A series of GRAB (G protein-coupled receptor activation‒based) sensors developed for detecting somatostatin (SST), cholecystokinin (CCK), corticotropin-releasing factor (CRF), neuropeptide Y (NPY), neurotensin (NTS), and vasoactive intestinal peptide (VIP).
• These fluorescent sensors utilize the corresponding GPCRs as the neuropeptide-sensing module with the insertion of a circular-permutated GFP as the optical reporter.
• This design detects the binding of specific neuropeptides at nanomolar concentration with a robust increase in fluorescence.
• These GRAB neuropeptide sensors are used to measure the spatiotemporal dynamics of endogenous SST release in isolated pancreatic islets and to detect the release of both CCK and CRF in acute brain slices.
• Moreover, endogenous CRF release induced by stressful experiences in vivo using fiber photometry and 2-photon imaging in mice are detected.
• Together, these new sensors establish a robust toolkit for studying the release, function, and regulation of neuropeptides under both physiological and pathophysiological conditions.