Neurexin drives C. elegans avoidance behavior independently of its post-synaptic binding partner Neuroligin

Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, and post-synapses, respectively, but less is known about their role in driving behaviors. Here, we use the nematode C. elegans to show that neurexin, but not neuroligin, is required for avoiding specific chemorepellents. We find that adults with knockouts of the entire neurexin locus exhibit a strong avoidance deficit in response to glycerol and a weaker defect in response to copper. Notably, the C. elegans neurexin (nrx-1) locus, like its mammalian homologs, encodes multiple isoforms, and {gamma}. Using isoform-specific mutations, we find that the {gamma} isoform is selectively required for glycerol avoidance. Next, we used transgenic rescue experiments to show that this isoform functions at least partially in the nervous system. We also confirm that the transgenes are expressed in the neurons and observe protein accumulation in neurites. Furthermore, we tested whether these mutants affect the behavioral responses of juveniles. We find that juveniles (4th larval stages) of mutants knocking out the entire locus or the -isoforms, but not {gamma}-isoform, are defective in avoiding glycerol. These results suggest that the different neurexin isoforms affect chemosensory avoidance behavior in juveniles and adults, providing a general principle of how isoforms of this conserved gene affect behavior across species. Article SummaryThe conserved neurexin locus can encode multiple isoforms via alternate splicing, but very little is known about the function of individual isoforms. We show that the C. elegans neurexin {gamma} isoform is specifically required for glycerol, but not copper or quinine avoidance in adults. In contrast, we find that , but not {gamma}, isoforms are required for avoiding glycerol in juveniles. Collectively, we suggest that different neurexin isoforms are required in juveniles and adults to modify chemosensory behavior.