Dissection of a sensorimotor circuit that regulates aversion to odors and pathogenic bacteria inC. elegansby whole-brain simulation

AbstractAltering behavior to reduce pathogen exposure is a key line of defense against pathogen attack for nearly all animals. The use ofCaenorhabditis elegansbacterial infection models have allowed for many insights into the molecular mechanisms of behavioral immunity. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown. We found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed toPseudomonas aeruginosaorEnterococcus faecalisshowed reflexive aversion to drops of the bacteria, requiring ASI, AWB, and AWC neurons and ASE, AWB, and AWC neurons, respectively. This response also involved intestinal distention and, forE. faecalis, required expression of TRPM channels in the intestine and excretory system. Using whole-brain simulation and functional assays, we uncovered a sensorimotor circuit governing learned reflexive aversion. This behavior is controlled by a four-layer neural circuit composed of olfactory neurons, interneurons, and motor neurons that control backward locomotion crucial for learned reflexive aversion to pathogenic bacteria, learned avoidance, and a repulsive odor. The discovery of a complete sensorimotor circuit for reflexive aversion demonstrates the utility of using theC. elegansconnectome and computational modeling in uncovering new neuronal regulators of behavior.