MetaFlex

A key emerging question in brain studies is how energy metabolism regulation intervenes in higher brain function to shape behavior. It is currently believed that, contrary to the peripheral organs, brain energy metabolism lacks fuel flexibility and under regular conditions must primarily rely on glucose metabolism to fulfill its enormous needs. Based on my recent research at the interface between memory and energy metabolism, and a strong body of preliminary data, I aim to challenge this view and establish that brain energy metabolism has the flexibility to rely on both sugars and lipids. Specifically, I propose that the combined consideration of the primary fuel source and of its cellular allocation to either neurons or glial cells defines a repertoire of discrete metabolic states involved in memory formation. Each metabolic state, implemented in a context-dependent manner, is specific to the to-be-formed memory, thus defining a ‘metabolic code of memory’. Because metabolic pathways are very well conserved during evolution, this project will use Drosophila melanogaster as a reference species, and it will take advantage of my expertise in behavioral studies and in vivo brain imaging. I propose to: 1) comprehensively characterize the metabolic states underlying the discrete phases of aversive memory, demonstrating in particular the relevance of fatty acids as an energy source in neurons. 2) investigate the intriguing role of reactive oxygen species signaling in building long-term memory. 3) unveil a novel role of neuropeptides in memory regulation, as mediators of the transitions between metabolic states. This project will thus make it possible to reconsider several established principles concerning brain energy metabolism, and to lead to a new conceptual framework for the formation and regulation of memory.