Thomas Preat earned his PhD at Orsay University in 1989 after studying the fused gene involved in drosophila embryonic development. He discovered the Suppressor-of-fused pathway. Following his PhD he changed field to study learning and memory using drosophila molecular genetics. From 1989-1992 he was a postdoctoral fellow in the laboratory of Dr Timothy Tully at Brandeis University (Waltham, MA, USA). During this time, Thomas Preat was the first to devise a protocol inducing associative long-term memory in drosophila. In 1992-1993 Thomas Preat joined the laboratory of Pr Martin Heisenberg (Würzburg, Germany) where he studied drosophila brain anatomy.
In 1994 he was awarded a CNRS position in France,and settled his team at the Alfred Fessard Neurobiology Institute (Gif, France). In 2006, his team moved to the ESPCI in Paris. The team, co-headed since 2019 by Pierre-Yves Plaçais, takes an integrated approach to study the interplay between olfactory memory and energy metabolism in drosophila. Thomas Preat was a pioneer in the study of glia-neuron interactions in relation to memory phases in drosophila. In connection with the study of brain energy metabolism, Thomas Preat is very interested in using drosophila to decipher the pathways involved in the early steps of Alzheimer’s disease. Thomas Preat was awarded an ERC Advanced grant in 2017. He received awards from the Foundation for Medical Research, the Schlumberger Foundation and the Schueller-Bettencourt Foundation. He was elected at EMBO in 2012.
The dual role of glia-neuron interactions for long-term memory: energy supply and regulation of redox homeostasis
A key emerging question is how energy metabolism intervenes in higher brain function to shape behavior. Given that defects in energy metabolism are increasingly thought to be causally involved in aging-induced memory impairments or neurodegenerative diseases, there is a high stake in decoding the implication of energy metabolism in brain plasticity.
Drosophila show an elaborate structure of memory phases, which are formed in a context- (i.e. conditioning experience) and state-dependent (i.e. feeding status, mating status, social environment) manner. In particular, our team showed that aversive long-term memory (LTM) formation is inhibited in the starvation state (1). Our recent work has highlighted the existence of causal relationships between the cellular organization of metabolism in neurons of the olfactory memory center, the mushroom body (MB), and glial cells (2,3).
Glucose is the primary source of energy for the brain. However, it remains controversial whether, upon neuronal activation, glucose is primarily used by neurons for ATP production, or if it is partially oxidized in astrocytes, as proposed by the astrocyte-neuron lactate shuttle model for glutamatergic neurons in the mammalian brain. Thus, an in vivo picture of glucose metabolism during cognitive processes is missing. I will show here that glucose plays a dual role during memory formation. First glucose is a source of energy for both short-term and long-term memory (LTM). Following associative conditioning, glycolysis in glial cells produces alanine, which is back-converted into pyruvate in mushroom body cholinergic neurons to uphold their increased mitochondrial needs (4). In addition, for LTM, specific dopaminergic signaling to the MB sustains mitochondrial activity after conditioning (1,4).
In parallel to providing energy via glia glycolysis, a dedicated glial glucose transporter transfers glucose to MB for LTM, for use by the pentose phosphate pathway (2). Our pioneer preliminary data suggest that the regulation of the pentose pathway is required to maintain redox homeostasis during LTM formation.
The delineation of glucose metabolism during memory formation indicates that specific metabolic hallmarks can be attributed to a given memory type. Importantly, these metabolic upregulations consistently occur in the early stage of memory formation, i.e. in a time window of a few hours after conditioning. Hence, these findings raise the exciting possibility that the brain could harbor metabolic signatures of the memories that are being encoded, which are crucial for proper memory formation as well as determining its persistence and other properties.
(1) Plaçais, P.-Y. and Preat, T. (2013). To favor survival under food shortage, the brain disables costly memory. Science, 339(6118):440-442.
(2) de Tredern, E., Rabah, Y., Pasquer, L., Minatchy, J., Plaçais, P.-Y., Preat T. (2021). Glial glucose fuels the neuronal pentose phosphate pathway for long-term memory. Cell Rep, 24;36(8):109620.
(3) Silva, B., Mantha, O. L., Schor, J., Pascual, A., Plaçais, P.-Y., Pavlowsky, A. and Preat, T. (2022). Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation. Nat Metab, 4(2):213-224.
(4) Plaçais, P.-Y., de Tredern, E., Scheunemann, L., Trannoy, S., Goguel, V., Han, K.-A., Isabel, G., and Preat, T. (2017). Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory. Nat Commun, 8:15510.
(5) Rabah, Y., Frances, R., Plaçais, P.-Y. and Preat, T. Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila (unpublished results).