Date of Award
Doctor of Philosophy (PhD)
Disease is accompanied by modifications to host behavior that promote recovery and survival. The neural and molecular mechanisms that rule the switch to a sickness behavioral state are an active area of research. One established model for sickness behavior is the interaction between Caenorhabditis elegans and the pathogenic bacteria Pseudomonas aeruginosa PA14. After a few hours of exposure to and infection by PA14, C. elegans develops a sickness-like behavior termed pathogen avoidance. Here I identify neuronal signals generated during the infection and associate them with antagonistic circuits that shape the host behavior. Using an unbiased cell-directed neuropeptide screen, I show that the AVK neurons release FMRFamide-like FLP-1 neuropeptides during infection to drive avoidance of pathogenic bacteria. Manipulations that increase or decrease AVK signaling accelerate or delay pathogen avoidance, respectively, implying an instructive role in the behavioral decision. FLP-1 neuropeptides act on the G-protein-coupled receptor DMSR-7 which drives pathogen avoidance by inhibiting tyraminergic and octopaminergic signaling from neurons that play multiple roles in the pathogen response. My results demonstrate that antagonism between neuromodulatory systems results in graded transitions between alternative behavioral states.
Marquina-Solis, Javier, "Peptidergic Signaling Controls the Dynamics of Sickness Behavior in Caenorhabditis Elegans" (2022). Student Theses and Dissertations. 744.