Critical roles of ERK and Akt signaling in metabolically dependent memory formation in Drosophila larvae

In the fruit fly Drosophila , memory formation is intricately linked to metabolic state. Our previous findings showed that the preferential support of memory under increased energy levels is mediated by the insulin receptor in the mushroom body (MB), a key memory center in the insect brain. This study analyzed the role of the insulin receptor’s downstream pathways, Ras-Raf-MEK-ERK and PI3K/Akt, in metabolically dependent memory formation. We evaluated their impact on memory processes by employing RNA interference-mediated downregulation of key components, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), in the MB of Drosophila larvae. To enhance energy levels, larvae were fed sugar for 60 minutes prior to aversive olfactory conditioning. Our findings revealed that genetically downregulating ERK and Akt in the MB significantly impaired metabolically dependent memory formation, without affecting naive sensory perception or olfactory learning. Immunohistochemical analysis confirmed the presence of active forms of ERK and Akt in the MB, underscoring their roles in modulating memory processes under elevated energy levels. The pivotal roles of these kinases suggest a broader implication of insulin signaling in memory formation under different metabolic conditions, and illuminate the connections between metabolic regulation and memory dynamics in the MB.