Emerging approaches for decoding neuropeptide transmission

Neuropeptides produce robust effects on behavior across species, and recent research has benefited from advances in high-resolution techniques to investigate peptidergic transmission and expression throughout the brain in model systems. Neuropeptides exhibit distinct characteristics which includes their post-translational processing, release from dense core vesicles, and ability to activate G-protein-coupled receptors (GPCRs). These complex properties have driven the need for development of specialized tools that can sense neuropeptide expression, cell activity, and release. Current research has focused on isolating when and how neuropeptide transmission occurs, as well as the conditions in which neuropeptides directly mediate physiological and adaptive behavioral states. Here we describe the current technological landscape in which the field is operating to decode key questions regarding these dynamic neuromodulators. Neuropeptides dynamically encode various physiological processes, including ones that contribute to behavioral state transitions.New tools and approaches to characterize neuropeptide transmission during behavior are now more commonly used.Neuropeptide transmission – from post-translational processes, packaging, release, localization, and receptor activation – is complex and difficult to measure at the systems level.A host of promising new dynamic sensors, pharmacological approaches, and hardware offer promising new windows into understanding neuropeptidergic transmission.