Animals can retain various kinds of information as memories to respond more effectively to environments. In addition, the memories should be forgotten depending on the environments, because some information is valuable only in particular conditions. Therefore, the memory retention should be adequately regulated by environmental conditions, although the regulatory mechanisms of forgetting remain unclear. C. elegans shows adaptation to diacetyl, which is one of the odorants sensed by AWA sensory neurons. We demonstrated that the TIR-1/JNK-1 pathway in AWC sensory neurons accelerated forgetting of the adaptation to diacetyl. In wild-type animals, the adaptation is sustained for less than 4 hours on food, whereas, in
tir-1 loss-of-function mutant, the adaptation persisted more than a day in the same condition. However, when, after conditioned with diacetyl, animals were incubated without food, both wild-type and
tir-1 (lf) animals were recovered from the adaptation within 4 hours. Furthermore,
ceh-36 mutant, which does not have functional AWC neurons, showed the prolonged retention of the adaptation regardless of with or without food. Therefore, we postulated that food signals, which are inhibited by TIR-1/JNK-1 pathway in AWC, inhibit forgetting. To elucidate the mechanisms for the regulation of the forgetting by the food signals, we carried out suppressor screening from
tir-1. We checked about 10,900 haploid genomes to search for the mutants showing the normal forgetting even when animals were cultivated on food after adaptation although
tir-1 (lf). We found that mutations in
dgk-1, which encodes a diacylglycerol kinase-1 involved in acetylcholine release by phosphorylation of diacylglycerol (DAG), suppress the phenotype of
tir-1. Next, we examined whether the known DAG pathway is involved in the forgetting of diacetyl adaptation using the double mutants with
tir-1. The behavioral assays after recovery showed that mutations in
dgk-3,
goa-1 (Goa), and
egl-30 (gf) (Gqa) suppressed the
tir-1 phenotype similarly to
dgk-1. These results suggest that the food signal regulates the forgetting of olfactory adaptation through the DAG pathways.