Dynamics and plasticity of neuropeptidergic circuits (360G-Wellcome-334063_Z_25_Z)

Neurons communicate with each other using two main modes of signaling: signal transmission via synaptic contacts (chemical and electrical synapses) and transmission via diffusible molecules, including neuropeptides, that can mediate signaling between neurons that are not directly connected by physical synapses. Understanding the spatiotemporal dynamics of these distinct routes of communication is essential to our understanding of brain function. While the dynamics of synaptic circuits are relatively well-studied, much less is known about the dynamics of "wireless" networks of peptidergic signaling. The proposed work will address fundamental questions about neuropeptide signaling in neural circuits: how fast and how far do peptidergic signals travel in nervous tissue?, how do they alter the patterns of activity in neural circuits?, how are converging neuropeptide pathways integrated in individual neurons?, and how is the dynamics of neuropeptides altered by changes in their expression? We will address these questions in the feeding circuit of the nematode C. elegans, where the dynamics of peptidergic signaling can be probed with cutting-edge optogenetic tools in live animals. We will also use human cell models to identify conserved principles of neuropeptide signaling that can be translated to understand human disease.