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Papers of the Week

Papers: 4 Feb 2023 - 10 Feb 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Non-Human Pain

2023 Feb 08



The C. elegans Innexin INX-20 Regulates Nociceptive Behavioral Sensitivity.


Chaubey AH, Sojka SE, Onukwufor JO, Ezak MJ, Vandermeulen MD, Bowitch A, Vodičková A, Wojtovich AP, Ferkey DM


Organisms rely on chemical cues in their environment to indicate the presence or absence of food, reproductive partners, predators or other harmful stimuli. In the nematode Caenorhabditis elegans, the bilaterally symmetric pair of ASH sensory neurons serve as the primary nociceptors. ASH activation by aversive stimuli leads to backward locomotion and stimulus avoidance. We previously reported a role for guanylyl cyclases in dampening nociceptive sensitivity that requires an innexin-based gap junction network to pass cGMP between neurons. Here we report that animals lacking function of the gap junction component INX-20 are hypersensitive in their behavioral response to both soluble and volatile chemical stimuli that signal through G protein-coupled receptor pathways in ASH. We find that expressing inx-20 in the ADL and AFD sensory neurons is sufficient to dampen ASH sensitivity, which is supported by new expression analysis of endogenous INX-20 tagged with mCherry via the CRISPR-Cas9 system. Although ADL does not form gap junctions directly with ASH, it does so via gap junctions with the interneuron RMG. Ablating either ADL or RMG also resulted in nociceptive hypersensitivity, suggesting an important role for RMG downstream of ADL in the ASH modulatory circuit. This work adds to our growing understanding of the repertoire of ways by which ASH activity is regulated via its connectivity to other neurons, and identifies a previously unknown role for ADL and RMG in the modulation of aversive behavior.