Abstract
Proper management of memories by forgetting and retrieval is essential for animals to adapt their behavior to changing environments. To elucidate the mechanisms underlying forgetting, we use olfactory learning to an attractive odorant, diacetyl, in Caenorhabditis elegans hermaphrodites as a model. In this learning paradigm, the TIR-1/JNK-1 pathway in AWC sensory neurons accelerates forgetting of the olfactory memory, which is stored as a sensory memory trace in AWA sensory neurons. Our genetic screening revealed that increased neuronal diacylglycerol in the olfactory neuronal circuit, by mutations in diacylglycerol kinase-1, egl-30 or goa-1, Gq and Go type G-proteins, suppresses the forgetting defect in the behavior of tir-1 mutants, although the calcium imaging analyses of the olfactory neurons revealed that the sensory memory trace to the odorant was maintained. In contrast, the expression of a gain-of-function goa-1 gene exclusively in AWC neurons caused a forgetting defect in behavior, although their sensory memory trace declined. Furthermore, the behavioral analysis of animals applied with diacylglycerol analog and measurement of diacylglycerol content by fluorescent imaging suggested that diacylglycerol content in AWC is important for the proper forgetting. These findings raise a possibility that diacylglycerol signaling plays a crucial role in determining whether to forget or to recall in olfactory learning.SIGNIFICANCE STATEMENT Forgetting and retrieval are important processes for proper management of memories, although the mechanisms underlying these processes remain largely unclear. We found that, in Caenorhabditis elegans, diacylglycerol signaling works in a forgetting mechanism downstream of TIR-1/JNK-1 pathway. Mutations that change diacylglycerol content in the olfactory neurons affect behavioral forgetting, although they did not alter the sensory memory trace. This suggests that diacylglycerol in specific neurons may determine the occurrence of retrieving, rather than modifying, the memory traces. Consistent with this hypothesis, application of diacylglycerol analog to animals suggests that diacylglycerol content until memory acquisition decides whether to retrieve or to forget the memory.