%0 Journal Article %T Spatial Memory Consolidation is Associated with Induction of Several Lysine-Acetyltransferase (Histone Acetyltransferase) Expression Levels and H2B/H4 Acetylation-Dependent Transcriptional Events in the Rat Hippocampus. %T HAT/H2B dynamics in spatial memory formation. %+ Laboratoire de signalisation moléculaire et neurodégénerescence %+ Service de Neurologie [Strasbourg] %+ Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC) %A Bousiges, Olivier %A Vasconcelos, Anne Pereira De %A Neidl, Romain %A Cosquer, Brigitte %A Herbeaux, Karine %A Panteleeva, Irina %A Loeffler, Jean-Philippe %A Cassel, Jean-Christophe %A Boutillier, Anne-Laurence %Z Fédération de la Recherche sur le Cerveau (FRC); INSERM, « Association pour la Recherche sur les Maladies Neurodégénératives » (AREMANE); France Alzheimer 67; University of Strasbourg, CNRS. %< avec comité de lecture %@ 0893-133X %J Neuropsychopharmacology %I Nature Publishing Group %P epub ahead of print %8 2010-09-01 %D 2010 %R 10.1038/npp.2010.117 %M 20811339 %K hippocampus-dependent memory %K CREB-binding protein CBP %K Histone acetyltransferase (HAT) %K H2B histone %K Morris water maze %K memory consolidation %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Numerous genetic studies have shown that the CREB-binding protein (CBP) is an essential component of long-term memory formation, through its histone acetyltransferase (HAT) function. E1A-binding protein p300 and p300/CBP-associated factor (PCAF) have also recently been involved in memory formation. By contrast, only a few studies have reported on acetylation modifications during memory formation, and it remains unclear as to how the system is regulated during this dynamic phase. We investigated acetylation-dependent events and the expression profiles of these HATs during a hippocampus-dependent task taxing spatial reference memory in the Morris water maze. We found a specific increase in H2B and H4 acetylation in the rat dorsal hippocampus, while spatial memory was being consolidated. This increase correlated with the degree of specific acetylated histones enrichment on some memory/plasticity-related gene promoters. Overall, a global increase in HAT activity was measured during this memory consolidation phase, together with a global increase of CBP, p300, and PCAF expression. Interestingly, these regulations were altered in a model of hippocampal denervation disrupting spatial memory consolidation, making it impossible for the hippocampus to recruit the CBP pathway (CBP regulation and acetylated-H2B-dependent transcription). CBP has long been thought to be present in limited concentrations in the cells. These results show, for the first time, that CBP, p300, and PCAF are dynamically modulated during the establishment of a spatial memory and are likely to contribute to the induction of a specific epigenetic tagging of the genome for hippocampus-dependent (spatial) memory consolidation. These findings suggest the use of HAT-activating molecules in new therapeutic strategies of pathological aging, Alzheimer's disease, and other neurodegenerative disorders.Neuropsychopharmacology advance online publication, 1 September 2010; doi:10.1038/npp.2010.117. %G English %2 https://inserm.hal.science/inserm-00516665/document %2 https://inserm.hal.science/inserm-00516665/file/Bousiges-HAL_inserm.pdf %L inserm-00516665 %U https://inserm.hal.science/inserm-00516665 %~ INSERM %~ CNRS %~ UNIV-STRASBG1 %~ UNIV-STRASBG %~ SITE-ALSACE