Distinct Behavioral Roles of D-Aspartate Oxidases DDO-1 and DDO-2 in Caenorhabditis elegans

D-amino acids are widely distributed across organisms, and their metabolism contributes to the regulation of neuronal activity and behavior. Whereas most animals possess one D-amino acid oxidase (DAAO) for neutral and basic D-amino acids and one D-aspartate oxidase (DDO) for acidic D-amino acids, the nematode Caenorhabditis elegans uniquely carries three DDOs. Previous studies showed that DDO-3 affects the nose touch response and that DAAO-1 regulates foraging behavior after food removal. However, the physiological roles of DDO-1 and DDO-2 had remained unclear. Here, we analyzed loss-of-function mutants to examine the behavioral roles of D-amino acid-oxidizing enzymes in C. elegans. The ddo-1 mutant displayed reduced responses to posterior body touch and a disrupted defecation rhythm, whereas the ddo-2 mutant exhibited increased forward movement duration and reduced reversal frequency during foraging immediately after food removal. In wild-type animals, dietary D-Asp supplementation reduced the posterior body touch response, and oxaloacetate restored the defecation defects of ddo-1 mutants. In addition, acidic amino acid supplementation altered foraging-related locomotor behavior in wild-type animals but not in ddo-2 mutants. All behavioral defects were rescued in the corresponding transgenic lines. Together, these results indicate distinct behavioral roles of D-amino acid-oxidizing enzymes in C. elegans.