Visualising the spatial range of neuropeptide action (360G-Wellcome-212525_Z_18_Z)

Our moods and our memories arise from a form of chemical communication in our brain termed neuromodulation. Neuromodulators are diffusible neurotransmitters, such as monoamines and neuropeptides, that can act at a distance and potentially reach many different circuits in the brain. Traditionally, neuropeptides have been thought to act on all receptor-expressing neurons within the brain. However, the fact that these molecules convey very specific information and that this information depends on the source of release, indicates that their spatial range of action must be actively regulated. The aim of this proposal is to develop a system for the in vivo visualisation of neuromodulation and the identification of mechanisms that regulate neuropeptide spatial range of action. For this we will exploit the advantages of C. elegans: transparency, single-cell resolution and amenability to genetics. We will first generate a reporter strain to visualise neuropeptide receptor activation upon controlled neuropeptide release, based on the TANGO assay. The novelty of our approach is to apply this tool to the study of neuropeptide target reach. Second, we will perform a forward genetic screen to identify regulators of neuropeptide spatial range of action by isolating mutants with changes in the pattern of neuropeptide receptor activation.