[
International Worm Meeting,
2021]
Animals acquire and store information as memories that are required for their behavior and decision-making. To mitigate undesirable effects of old information stored in their brain, they must forget some dispensable memories. However, molecular mechanisms in forgetting are still unclear. To investigate the mechanisms of forgetting, we use olfactory learning in Caenorhabditis elegans (C. elegans) as a model. C. elegans is highly attracted to some odorants such as diacetyl, although, after prolonged exposure to odorants without food, the animals adapt to the odorants and show weak chemoattraction. The adapted animals can regain their chemoattraction after the cultivation on food for several hours. Previously, our studies showed that TIR-1/JNK-1 pathway in AWC sensory neurons accelerates forgetting of olfactory memory through releasing of "forgetting signals". However, the molecular basis of "forgetting signals" remains elusive. In this study, we identified a substance of "forgetting signals" through a reverse genetic approach. Firstly, to check the possibility that neuropeptides work as "forgetting signals", we analyzed forgetting phenotypes in mutants of neuropeptide processing enzymes, and found that mutants of various neuropeptide-processing enzymes showed forgetting defect, suggested that neuropeptides might be responsible for "forgetting signals". Furthermore, to identify the neuropeptides that serve as "forgetting signals" secreted from AWC sensory neurons, we searched for candidate genes by using a database of single-cell RNA sequencing, CeNGEN (C. elegans Neuronal Gene Expression Network), and identified 12 candidate neuropeptide genes. By genome editing using CRISPR-Cas9, we created these mutants and analyzed their forgetting phenotype. Among these candidates, mutants of one neuropeptide gene showed forgetting defect. Moreover, injection of the genomic fragments derived from wild type could recover the forgetting phenotype in these mutants. These results suggest that this neuropeptide is responsible for accelerating forgetting. Further analyses of its function will reveal how memory forgetting are regulated through signaling pathways including "forgetting signals" and its receptors.