Energy & Memory lab

Constraints on energy efficiency throughout evolution have resulted in highly conserved networks of metabolic pathways underlying the function of all eukaryotic cells.
Brain cells, neurons and glia, are no exception to this, and pioneer works, including ours, outline that metabolic regulations are key players of brain cellular physiology, neuronal plasticity, and the resulting behaviors.
Our Energy & Memory team is globally interested in the still little-explored interaction between energy metabolism and memory formation. We use Drosophila melanogaster as a working species, leveraging both the unique panoply of genetic-based analytical tools, and the exquisite knowledge of neuronal circuits underlying olfactory associative memory from decades of research. We can therefore achieve precise in vivo manipulation and measurement of biochemical pathways in a cell-specific manner, in relation to behavior. Our strategy combines neurogenetics, behavior analysis and in vivo brain imaging using genetically encoded fluorescent probes.

Through our integrated approach, we uncovered different patterns of learning-induced activation of metabolic pathways in the mushroom body, the brain center encoding olfactory memory in Drosophila. Addressing these questions in the ‘simple’ Drosophila brain is a powerful way to uncover novel and unexpected basic mechanisms to generate hypotheses testable in other species.

1. Neuron-glia metabolic interactions underlying memory formation
2. Plasticity of the neuronal mitochondrial network associated with memory formation
3. State- and experience-dependent regulation and coordination of cellular metabolism by neuropeptides
   

Another major objective of our team is to contribute to deciphering the molecular and cellular disorders that are at the root of Alzheimer’s disease (AD). AD is a multifactorial progressive neurodegenerative condition characterized by a long asymptomatic phase, during which defects in brain energy metabolism is observed. The origin of AD remains obscure, and a key question is: how does the human brain transition from a physiological to a pathological state years before memory impairment becomes apparent?
We have discovered in Drosophila a new synaptic plasticity pathway involves in long-term memory formation termed ANHOS (Astrocyte-to-Neuron H₂O₂ Signaling), which is impaired by human amyloid-ß (Rabah et al. 2025). We propose a new framework for studying the origin of AD, which would be linked to a lack of beneficial reactive oxygen species.
We aim to:

• Decipher ANHOS physiology and investigate how its impairment leads to many AD hallmarks
• Demonstrate that the major genetic risk factor APOE4 impairs ANHOS
• Propose new avenues for AD treatment