The NALCN regulator UNC-80 functions in a subset of interneurons to affect C. elegans avoidance response to the plant hormone methyl salicylate

NALCN ( leak hannel, on-selective), UNC80 and UNC79 form a non-selective, voltage-independent cation channel complex that affects a broad array of neuronal activities. The molecular and neuronal mechanisms underlying the functions of the NALCN complex remain unclear. In a screen for mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated novel loss-of-function (lf) mutations in and . and lf mutants exhibited defective MeSa avoidance but wild type-like responses to other odorants. Lf mutants of exhibited similar MeSa-specific avoidance defect, while lf mutants of the NALCN regulatory gene avoided MeSa like wild type. Using fluorescent transgenic animals, we identified a subset of -expressing neurons. Neuron-specific transgene rescue and knockdown experiments suggest that a subset of interneurons, primarily including AVA, AVE and AVG, might play a necessary and sufficient role in mediating regulation of the MeSa avoidance. We found that was expressed in neurons largely overlapping those expressing , which is supported by the rescue of defects using an transgene driven by an promoter. We also suggest that locomotion responds more sensitively to the changes of expression levels of -related genes than the MeSa avoidance does. Together, our results identified NALCN-related genes as key regulators of the MeSa avoidance behavior and provided novel genetic and neuronal insights into the function of the NALCN channel complex.