Animals should properly control the retention time of memory in order to adapt to constantly changing environments. Therefore, the process for active forgetting of dispensable memories is important for survival. However, the regulatory mechanisms of active forgetting remain to be understood. We previously reported that the TIR-1/JNK-1 pathway in AWC sensory neurons accelerates forgetting of the adaptation to diacetyl, which is one of the odorants sensed by AWA sensory neurons. Wild-type animals forget the adaptation after incubated on food. In contrast,
tir-1 mutants show prolonged retention of the adaptation after incubated on food. Therefore, to explore the downstream factors of the TIR-1/JNK-1 pathway, we carried out a suppressor screening of the forgetting phenotype of a
tir-1 loss-of-function mutant. Consequentially, we found that mutations in
dgk-1, which encodes a diacylglycerol kinase-1, suppress the phenotype of
tir-1. DGK-1 is known to interfere with synaptic release by phosphorylation of diacylglycerol (DAG). Next, we examined whether the known DAG signaling pathway is involved in the forgetting of the adaptation to diacetyl. Mutations in
dgk-3 (diacylglycerol kinase-3),
goa-1 (Go?), and
egl-30 (gf) (Gq?) suppressed the
tir-1 phenotype similarly to in
dgk-1. These results suggest that DAG signaling pathway presumably regulates the forgetting downstream of TIR-1/JNK-1 pathway. Furthermore, the cell-specific rescue experiments of
goa-1 gene showed that the expressions of
goa-1 in AWB and AWC sensory neurons, or AIA interneurons were sufficient to restore the forgetting phenotype. On the other hand, after recovery without food,
tir-1 mutants can forget the memory for olfactory adaptation similarly to wild-type animals. Interestingly,
goa-1 mutants and their double mutants with
tir-1 exhibited prolonged retention of the adaptation after incubated without food, in contrast to after incubated on food. In addition, mutants for a biosynthetic enzyme and receptors for serotonin showed a defect in forgetting after recovery without food, suggesting that serotonin is important for the regulation of forgetting. Taken together, active forgetting of memories made by simple learning paradigm is properly regulated through several neuronal processes.