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
Affiliations
Javier Marquina-Solis
Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA
Likui Feng
Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA
Elke Vandewyer
Department of Biology, KU Leuven, 3000 Leuven, Belgium
Isabel Beets
Department of Biology, KU Leuven, 3000 Leuven, Belgium
Josh Hawk
Program in Cellular Neuroscience, Neurodegeneration and Repair, Departments of Neuroscience and of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA
Daniel A. Colón-Ramos
Program in Cellular Neuroscience, Neurodegeneration and Repair, Departments of Neuroscience and of Cell Biology, Yale University School of Medicine, New Haven, CT 06511, USA; Instituto de Neurobiología José del Castillo, Recinto de Ciencias Médicas, Universidad de Puerto Rico, San Juan, PR 00901, USA; Wu Tsai Institute, Yale University, New Haven, CT 06510, USA
Jingfang Yu
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Bennett W. Fox
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Frank C. Schroeder
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Cornelia I. Bargmann
Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, NY 10065, USA; Corresponding author
Summary: 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.
