[
International Worm Meeting,
2021]
Past experiences, moods and emotions change our behaviours, partly due to the neuromodulation of underlying circuits from neuropeptides. Neuropeptides are secreted, diffusible proteins that act on G-protein coupled receptors (GPCRs), providing long-lasting modulation to hard-wired neuronal circuits. Most neuropeptide receptor expressing neurons are not synaptically connected to the source, thus, the expression patterns of the ligand and its receptors represent a wireless chemical connectivity map that work in conjunction with traditional synaptic communication. Neuropeptides regulate many global states as well as more discrete modulatory functions such as learning and memory. However, it is unknown how neuropeptides encode such diverse information. For global behavioural state changes, it is thought neuropeptides may activate any target they reach in their diffusion pathway, a process termed volume transmission. For functions that require specific target modulation, such as associative learning, emerging evidence suggests diffusion could be more regulated and controlled (van den Pol 2012), however mechanisms underlying this regulation are unknown. Many affective disorders rely on exogenous application of neuromodulators, therefore improving our understanding of neuropeptide diffusion regulation, could reduce adverse side effects many patients suffer due to off-target activity. We are employing C. elegans to establish an in vivo system to visualise neuropeptide based neuronal communication to use as a tool to identify molecular and cellular regulators of neuropeptide diffusion. We are focusing on Pigment Dispersing Factor-1 (PDF-1) and its receptor PDFR-1, a highly conserved neuropeptide involved in a broad array of behaviours. By harnessing GPCR signalling cascades, we will introduce a synthetic pathway that converts the interaction between PDF-1 and PDFR-1 into a fluorescent signal, without interfering with endogenous signalling. We will control PDF-1 expression and secretion in a ligand-null mutant by co-expressing PDF-1 and channelrhodopsin in one neuronal source. This expression pattern will be used as the basis for a forward genetic screen. This project aims to create a system to visualise neuropeptide modulation in vivo which will set the foundation for an in-depth investigation to understand neuropeptide spatial range of action.