Extensive research has shown that the hippocampus and striatum have dissociable roles in memory and are necessary for "place" and "response" learning, respectively. In the present study, rats were trained on a cross maze task that could be solved by either a place or a response strategy, and the strategy used was determined by a probe trial. Phosphorylated cAMP response element-binding protein (pCREB) and c-Fos immunoreactivity (IR) were measured in the hippocampus and striatum either immediately or 1 hr after cross maze training. Immediately after training, pCREB-IR and c-Fos-IR were significantly higher in the hippocampus and striatum of trained rats than in control rats matched for motor activity, but the increase was independent of the strategy revealed at probe. One hour after training, however, pCREB-IR and c-Fos-IR were sustained in the hippocampal pyramidal and granule cell layers of place learners but returned to basal levels among response learners. In addition, pCREB-IR was sustained in the dorsomedial and dorsolateral striatum of response learners but returned to basal levels among place learners. There were no differences between place and response learners in c-Fos-IR in the striatum at either time point. The present results indicate that cross maze training causes an initial activation of transcription factors in both the hippocampus and striatum. Formation of memory for a place strategy, however, is related to sustained phosphorylation of CREB and expression of c-Fos for at least 1 hr in the hippocampus, whereas formation of memory for a response strategy is related to phosphorylation of CREB in the striatum.
A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB-and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.Rats and mice exhibit age-related impairments in learning and memory on many tasks. Often, the impairments can be characterized in terms of rapid forgetting, in which aged rats and mice have relatively comparable learning and memory on tests soon after training, but poor memory at later times after training (Barnes and McNaughton 1985;
ABSTRACT:In the present study, phosphorylation of cAMP-response element binding protein (pCREB) and expression of c-Fos were measured in the dorsal and ventral hippocampus, as well as in a control region, the retrosplenial cortex, of rats following acquisition and recall of a socially transmitted food preference (STFP). Behavioral analyses revealed that STFP-trained rats showed a stronger preference for the demonstrated food than did rats in social-control or odor-control conditions. Rats in a social ؉ odor control condition displayed an intermediate preference that was not significantly different from either STFP-trained rats or the socialor odor-controls. Immunocytochemical analyses revealed increased pCREB-immunoreactivity (ir) in the ventral hippocampus of STFP-trained rats in comparisons with rats in all three control conditions and increased pCREB-ir in the dorsal hippocampus in comparisons with the social-and odor-control conditions. In contrast, c-Fos-ir was greater in the dorsal hippocampus of STFP-trained rats in comparisons with all three control conditions and greater in the ventral hippocampus than rats in the socialand odor-control conditions. Comparisons of pCREB-ir and c-Fos-ir were made also between STFP-trained rats and social-controls following either acquisition or a 48-h recall test. c-Fos-ir was greater in STFP-trained rats after both acquisition and recall, whereas pCREB was greater after recall only. There were no differences in either c-Fos-ir or pCREB-ir in comparisons between trained and control rats in the retrosplenial cortex. The current results indicate that the activity of transcription factors in the hippocampus is related to both acquisition and retention of a socially transmitted food preference.
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