The cumulative results of the present experiments show that CREB is essential for long-term memory formation in both the hippocampus and striatum. First, CREB activation was shown to be selective to brain regions specialized for different forms of memory processing. Increased phosphorylated CREB levels were sustained in the hippocampus of rats choosing a hippocampal-dependent place strategy whereas increased phosphorylated CREB levels were sustained in the striatum of rats choosing a striatal-dependent response strategy. Second, basal hippocampal CREB levels were shown to be decreased in a rat model system of hippocampal dysfunction and long-term memory impairment. Third, blocking CREB function in either the hippocampus or striatum suppressed long-term memory formation in a hippocampal- or striatal-dependent task, respectively. Fourth, increasing levels of CREB in the hippocampus facilitated long-term memory in a hippocampal-dependent task. Finally, the results shown here reveal that enhancing or blocking CREB function is only successful in altering memory formation if CREB is manipulated in the brain region that supports the type of memory being measured. Taken together, the results support the hypothesis that the hippocampus and striatum are central structures of two independent memory systems that simultaneously acquire information from the environment. The behavior that is produced is mediated by the brain system most congruent with the incoming stimuli
