• epigenetic;
  • hippocampus;
  • striatum;
  • aging;
  • memory

Epigenetic processes, such as histone acetylation, are critical regulators of learning and memory processes. In the present study, we investigated whether training in either a spatial or a cued water maze task undergoes selective changes of histone H3 and H4 acetylation within the hippocampus and the dorsal striatum of C57BL/6 mice. We also attempted to provide new insights into the relationships between deregulation in histone acetylation and age-associated memory deficits. In young mice, spatial training increased acetylation of histones H3 and H4 selectively in the dorsal hippocampal CA1 region and the dentate gyrus (DG) whereas cued training significantly enhanced acetylation of both histones selectively in the dorsal striatum. Our data also revealed age-related differences in histone acetylation within the hippocampus and striatum according to task demands. Specifically, age-related spatial memory deficits were associated with opposite changes of H3 (increase) and H4 (decrease) acetylation in CA1 and DG. After cued learning, both histone acetylation levels were reduced in the striatum of aged mice compared with corresponding young-adults but remained well above those of cage-controls. Collectively, our findings suggest an important role for histone acetylation in regulating the relative contributions of the hippocampus and striatum to learning spatial and cued memory tasks. © 2013 Wiley Periodicals, Inc.