Antagonism between neuropeptides and monoamines in a distributed circuit for pathogen avoidance

Area of Science:

• Neuroscience
• Behavioral Biology
• Infectious Disease

Background:

• Pathogenic infections necessitate host behaviors for survival.
• Caenorhabditis elegans exhibits modified sensory preferences to avoid Pseudomonas aeruginosa PA14 post-infection.

Purpose of the Study:

• To identify the neuromodulators responsible for acquired pathogen avoidance behavior.
• To elucidate the neural circuits and molecular mechanisms underlying pathogen avoidance.

Main Methods:

• Utilized an unbiased cell-directed neuropeptide screen.
• Manipulated AVK neuron activity and FLP-1 neuropeptide levels.
• Investigated the role of G protein-coupled receptor DMSR-7 and tyraminergic/octopaminergic neurons.

Main Results:

• AVK neurons upregulate and release FLP-1 neuropeptides during infection, driving pathogen avoidance.
• Increased AVK activity accelerates avoidance; decreased activity delays it.
• FLP-1 acts via DMSR-7 and other receptors, influencing tyraminergic/octopaminergic neurons receiving DAF-7 signals.

Conclusions:

• Antagonistic neuromodulators, specifically FLP-1, critically shape acquired pathogen avoidance.
• Pathogen avoidance involves complex neural circuits and multiple neuromodulatory targets.
• Findings align with the distributed neuromodulatory connectome of C. elegans.