RT Journal Article SR Electronic T1 Two components of aversive memory in Drosophila, anesthesia-sensitive and anesthesia-resistant memory, require distinct domains within the Rgk1 small GTPase JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3648-16 DO 10.1523/JNEUROSCI.3648-16.2017 A1 Satoshi Murakami A1 Maki Minami-Ohtsubo A1 Ryuichiro Nakato A1 Katsuhiko Shirahige A1 Tetsuya Tabata YR 2017 UL http://www.jneurosci.org/content/early/2017/05/02/JNEUROSCI.3648-16.2017.abstract AB 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.SIGNIFICANCE STATEMENTMemory 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.