Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus at the epigenomic, proteomic, and metabolomic levels. Caffeine lowered metabolism-related processes (e.g., at the level of metabolomics and gene expression) in bulk tissue, while it induced neuron-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through fine-tuning of metabolic genes, while boosting the salience of information processing during learning in neuronal circuits.


Isabel Paiva, Lucrezia Cellai, Céline Meriaux, Lauranne Poncelet, Ouada Nebie, Jean-Michel Saliou, Anne-Sophie Lacoste, Anthony Papegaey, Hervé Drobecq, Stéphanie Le Gras, Marion Schneider, Enas M. Malik, Christa E. Müller, Emilie Faivre, Kevin Carvalho, Victoria Gomez-Murcia, Didier Vieau, Bryan Thiroux, Sabiha Eddarkaoui, Thibaud Lebouvier, Estelle Schueller, Laura Tzeplaeff, Iris Grgurina, Jonathan Seguin, Jonathan Stauber, Luisa V. Lopes, Luc Buée, Valérie Buée-Scherrer, Rodrigo A. Cunha, Rima Ait-Belkacem, Nicolas Sergeant, Jean-Sébastien Annicotte, Anne-Laurence Boutillier, David Blum


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