Dissection of a sensorimotor circuit underlying pathogen aversion in C. elegans

Abstract

Background Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown. Results Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops of the bacteria driven by chemosensory neurons, including the olfactory AWB neurons. This response also involved intestinal distention and, for E. faecalis, required expression of TRPM channels in the intestine and excretory system. Additionally, we uncovered a circuit composed of olfactory neurons, interneurons, and motor neurons that controls the backward locomotion crucial for learned reflexive aversion to pathogenic bacteria, learned avoidance, and the repulsive odor 2-nonanone. Conclusions Using whole-brain simulation and functional assays, we uncovered a novel sensorimotor circuit governing learned reflexive aversion. The discovery of a complete sensorimotor circuit for reflexive aversion demonstrates the utility of using the C. elegans connectome and computational modeling in uncovering new neuronal regulators of behavior.

Neuronal basis and diverse mechanisms of pathogen avoidance in Caenorhabditis elegans

“…Backward locomotion is necessary during aversive reflection. This is controlled by the AWB neuron-mediated learned reflexive aversion circuit, which goes from sensory neurons AWB to interneurons AUA/RMG, progresses to lower-layer interneurons AVA/AVD/AVE, and ultimately reaches motor neurons VA/DA/AS/VA/DD ( 34 ).…”

“…Additionally, GON-2 and GTL-2, two transient receptor potential melastatin channels, have been identified as mediators of this avoidance response ( 104 ). The sensorimotor circuit for learned avoidance of EF is initiated by the AWB sensory neurons, proceeding through the interneurons AUA/RMG, extending to the lower layer interneurons AVA/AVD/AVE, and ultimately reaching the motor neurons VA/DA/AS/VA/DD ( 34 ).…”

Beyond mechanism – extending our concepts of causation in neuroscience

“…This interventionist approach is seen as the gold standard for detecting causality in the world (Pearl, 2009;Woodward, 2008) and it has led to some striking results in the study of organismal behavior. Using these techniques, researchers have been able to identify neural states that appear both necessary and sufficient for a specific behavior to occur (e.g., Castaneda et al, 2024;Filipowicz et al, 2022;Siemian et al, 2021). Sufficient in the sense that, when the neural state is optogenetically induced, it reliably results in specific behaviors or changes to cognitive operations, even in incongruent contexts.…”