Time-dependent relationship between the dorsal hippocampus and the prefrontal cortex in spatial memory.

The prefrontal cortex and the dorsal hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.