An Extensive Gap Junction Neural Network Modulates Caenorhabditis elegans Aversive Behavior

Background/Objectives: Caenorhabditis elegans rely on sensory perception of environmental cues for survival in their native soil and compost habitats. These cues provide information about nutrient availability, mating partners, or predatory and hazardous beacons. In C. elegans, the two bilaterally-symmetric head sensory neurons termed ASH are the main detectors of aversive nociceptive signals. Through their downstream connections in the nervous system, ASH activation causes the animal to initiate backward locomotion to escape and avoid the harmful stimulus. Modulation of avoidance behavior allows for situation-appropriate sensitivity and response to stimuli. We previously reported a role for gap junctions in the transport of regulatory cGMP to the ASHs where it functions to dampen avoidance responses. Methods: Here, we used genetic mutants and a combination of cell-selective rescue and knockdown experiments to identify gap junction proteins (innexins) involved in modulating ASH-mediated nociceptive behavioral responses. Results: We have characterized six additional C. elegans innexins that have overlapping and distinct roles within this regulatory network: INX-7, INX-15, INX-16, INX-17, UNC-7, and UNC-9. Conclusions: This work expands our understanding of the extent to which ASH sensitivity can be tuned in a non-cell-autonomous manner.