For aversive olfactory memory in Drosophila, multiple components have been identified that exhibit different stabilities. These components have been defined by behavioral and genetic studies, and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies (MBs), which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact.
Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila, Rgk1, that plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation.
The authors declare no competing financial interests.
We thank M. Saitoe, M.Heisenberg, H.Tanimoto, Y.Aso, A.Sugie and T.Miyashita for providing fly strains and reagents; the Kyoto Drosophila Genetic Resource Center (DGRC), the National Institute of Genetics, the Bloomington Drosophila Stock Center (BDSC), the Berkeley Drosophila Genome Project, the Exelixis Collection and the Developmental Studies Hybridoma Bank (DSHB) for reagents; H.Tarui and K.Kurimoto for coaching us with the RNA experiments; members of Tabata Laboratory for valuable comments and discussions. This research was supported by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (20115005 and 25115008 to T.T. and S.M.), Japan Society for the Promotion of Science (15K06700 to S.M.), Takeda Science Foundation (to T.T.), the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from MEXT (to K.S.), and Japan Agency for Medical Research and Development (AMED) (to K.S.).