Post-training intrahippocampal inhibition of class I histone deacetylases enhances long-term object-location memory

Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance long-term memory have focused on the fear-conditioning task using broad-spectrum HDAC inhibitors. We have found that post-training intrahippocampal administration of the broad-spectrum HDAC inhibitor trichostatin A (TSA) or the class I HDAC-selective inhibitor MS275 enhances long-term object-location memory, supporting a role for class I HDACs in the enhancement of hippocampus-dependent memory induced by HDAC inhibition.