Franz, H. R. | Search bioRxiv

bioRxiv2024

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 receptors 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.

neuroscience↗

bioRxiv2019

Insulin signaling gates long-term memory formation in Drosophila larvae

The ability to learn new skills and to store them as memory entities is one of the most impressive features of higher evolved organisms. However, not all memories are created equal; some are short-lived forms, and some are longer lasting. Formation of the latter is energetically costly and by the reason of restricted availability of food or fluctuations in energy expanses, efficient metabolic homeostasis modulating different needs like survival, growth, reproduction, or investment in longer lasting memories is crucial. Whilst equipped with cellular and molecular pre-requisites for formation of a protein synthesis dependent long-term memory (LTM), its existence in the larval stage of Drosophila remains elusive. Considering it from the viewpoint that larval brain structures are completely rebuilt during metamorphosis, and that this process depends completely on accumulated energy stores formed during the larval stage, investing in LTM represents an unnecessary expenditure. However, as an alternative, Drosophila larvae are equipped with the capacity to form a protein synthesis independent so-called larval anaesthesia resistant memory (lARM), which is consolidated in terms of being insensitive to cold-shock treatments. Motivated by the fact that LTM formation causes an increase in energy uptake in Drosophila adults, we tested the idea of whether an energy surplus can induce the formation of LTM in the larval stage. Indeed, increasing the metabolic state by feeding Drosophila larvae the disaccharide sucrose directly before aversive olfactory conditioning led to the formation of a larval LTM (lLTM). Moreover, we show that the metabolic state acts as a binary switch between the formation of lARM and lLTM. Based on this finding, we determined that it is the insulin receptor (InR) expressed in the mushroom body Kenyon cells (MB KCs) that mediates this switch to favor the formation of lLTM under energy-rich circumstances and lARM under energy-poor circumstances.

neuroscience↗