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

Javier Marquina-Solis | Likui Feng | Elke Vandewyer | Isabel Beets | Josh Hawk | Daniel A Colón-Ramos | Jingfang Yu | Bennett W Fox | Frank C Schroeder | Cornelia I Bargmann
Cell reports | 2024

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the nematode Caenorhabditis elegans modifies its sensory preferences to avoid the pathogen. Here, we identify antagonistic neuromodulators that shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, we show that AVK neurons upregulate and release RF/RYamide FLP-1 neuropeptides during infection to drive pathogen avoidance. Manipulations that increase or decrease AVK activity accelerate or delay pathogen avoidance, respectively, implicating AVK in the dynamics of avoidance behavior. FLP-1 neuropeptides drive pathogen avoidance through the G protein-coupled receptor DMSR-7, as well as other receptors. DMSR-7 in turn acts in multiple neurons, including tyraminergic/octopaminergic neurons that receive convergent avoidance signals from the cytokine DAF-7/transforming growth factor β. Neuromodulators shape pathogen avoidance through multiple mechanisms and targets, in agreement with the distributed neuromodulatory connectome of C. elegans.

Pubmed ID: 38573858

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM131877

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