Martínez G Vidal RL Mardones P Serrano FG Ardiles AO Wirth C Valdés P Thielen P Schneider BL Kerr B Valdés JL Palacios AG Inestrosa NC Glimcher LH Hetz C 2016 Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. application/pdf https://sonar.ch/global/documents/96967 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.01.028 info:eu-repo/semantics/altIdentifier/pmid/26854229 info:eu-repo/semantics/openAccess Cell reports. - 2016 Animals Brain-Derived Neurotrophic Factor Diacylglycerol O-Acyltransferase Endoplasmic Reticulum Endoplasmic Reticulum Stress Evoked Potentials Gene Expression Profiling Gene Expression Regulation, Developmental Hippocampus Long-Term Potentiation Male Memory Mice Mice, Knockout Molecular Sequence Annotation Neurons Promoter Regions, Genetic Signal Transduction Unfolded Protein Response X-Box Binding Protein 1 Regulation of Memory Formation by the Transcription Factor XBP1. http://purl.org/coar/resource_type/c_6501