Grabbing neuropeptide signals in the brain

CommunicatIon between neurons in the brain involves the release of either fast (for example, glutamate, γ-aminobutyric acid) or slow neurotransmitters (for example, catecholamines, histamine) from the presynaptic terminal, alone or together with neuromodulators. Fast neurotransmitters induce ion currents in the postsynaptic neuron. By contrast, slow neurotransmitters and neuromodulators act on metabotropic G protein–coupled receptors (GPCRs) in the postsynaptic membrane to trigger intracellular second messenger cascades. Neuropeptides are a superfamily of neuromodulators—more than 100 have been identified . However, studying neuropeptides is challenging owing to the limitations of available tools for their detection. Furthermore, despite decades of drug development aimed at neuropeptide-GPCRs, neither their localization nor the dynamics of ligand-induced activation is sufficiently understood. On page 786 of this issue, Wang et al. (1) describe GPCR-activation–based sensors (GRABs) that can track neuropeptide action in vivo. Such GRABs have the potential to provide new information on physiological processes (2) and the role of GPCRs in brain diseases.