In the early process of long-term memory formation, cyclic AMP response element-binding protein (CREB), a transcription factor on which multiple signal transduction pathways converge, has been implicated. We examined whether the age difference in the performance of contextual fear conditioning (CFC) is associated with a change in activation of CREB in the hippocampus which is an important neural structure for long-term memory. The activation of CREB in the hippocampus in young (15 weeks old) and old (120 weeks old) male rats was determined immunohistochemically with an antibody that specifically recognizes the phosphorylated form of CREB (pCREB). Young rats exhibited better performance than old rats with respect to the freezing time in CFC. Phosphorylation of CREB as revealed by the ratio of the pCREB-immunoreactive cell number to the CREB-immunoreactive cell number was increased in the CA1 region, but not in other hippocampal regions following training for CFC. The close relationship between behavioral performance and CREB phosphorylation in the CA1 region suggests that hippocampal CREB is involved in age-related decline of learning and memory.
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