An acquired short-term memory is usually disappeared within hours if not consolidated into a stable long-term memory. However, the mechanisms of the forgetting processes remain largely unknown. Since C. elegans possesses a simple nervous system and their memories usually do not persist more than hours, it is suitable to study the mechanisms of forgetting processes at the molecular level. To identify the gene that regulates those processes, we isolated a mutant
qj56 whose memories for the olfactory adaptation and the salt chemotaxis learning retained longer than those in wild type animals. In the
qj56 mutant, the memory for the olfactory adaptation was extended from a few hours to more than one day, and the memory for the salt chemotaxis learning was also prolonged. We found that
qj56 is an allele of
tir-1, which encodes an ortholog of human SARM, a Toll interleukin 1 receptor (TIR) domain protein. In C. elegans, TIR-1 regulates innate immune responses and asymmetric expression of STR-2 in the AWC sensory neurons via the P38/MAPK pathway. We found that mutants of CaMKII(UNC-43),
p38/JNK MAPKKK(NSY-1), MAPKK(SEK-1), and the JNK-1 show defects in forgetting processes.
In the salt chemotaxis learning, the forgetting defect of
tir-1 mutants was rescued by wild type
tir-1 gene with
zig-5 promoter, which drives expression in some sensory and inter-neurons. In the olfactory adaptation, the forgetting defect of
tir-1 mutants could be rescued by the expression of the wild type TIR-1 only in the AWC sensory neurons. In addition,
ceh-36 mutants, in which the functional AWC sensory neurons were lost, also showed prolonged retention of memory for the olfactory adaptation, suggesting that P38/JNK signals in AWC sensory neurons regulate forgetting processes for the olfactory adaptation in C. elegans. Although, TIR-1 regulates both forgetting and left-right asymmetry of AWC neurons, both
nsy-5 mutants, which did not express STR-2 in both AWC neurons (2AWCoff ), and
nsy-5 mutants overexpressing
olrn-1 gene, which express STR-2 in both AWC neurons (2AWCon ), did not show prolonged retention of memory, suggesting that AWCon or AWCoff cells can regulate the forgetting process adequately. These results indicate that the P38/JNK MAP kinase pathways in the AWC sensory neurons actively regulate the forgetting processes for the olfactory adaptation, probably by secreting signals that induce forgetting.