AGE-RELATED WORKING MEMORY DEFICITS DETECTED IN MICE PERFORMING WATER MAZE TASKS
B. Scruggs *1, J. Aniya2, K.C. Wright2, and K.R. Magnusson2
Dept. of Psychology1, Dept. of Anatomy & Neurobiology2, Colorado State University, Fort Collins, CO 80523
The prefrontal cortex shows greater changes during aging in volume and N-methyl-D-aspartate (NMDA) receptor expression than other areas involved in learning and memory. Working memory is one of the important functions of the prefrontal cortex. The purpose of this study was to determine whether aged mice, that typically show changes in prefrontal cortex in NMDA receptor expression during aging, exhibit working memory deficits. We used 3, 10, and 24-26 month old C57Bl/6 mice for this studies. We adapted a working memory task for aged rats using the Morris water maze from Shukitt-Hale et al. (Exp. Gerontol. 33: 615-624, 1998) and used it to examine immediate and delayed (10 minutes) working memory. In the first experiment, mice were tested for spatial reference memory for 12 days, followed by 4 days of spatial working memory testing. The working memory task consisted of 2 sessions per day with the hidden platform location changing each session. For each session, the mouse was placed on the new platform location for 30 seconds, swum for up to 60 seconds in an immediate trial, rested in the cage for 10 minutes and swum again for up to 60 seconds in the delayed trial. Twenty-four month old mice had significantly poorer performances in the reference memory task and in the immediate working memory task, but the difference in performance in the delayed trial did not reach significance. There was not a consistent improvement between immediate and delayed trials in the young mice with this protocol and there was no way to judge improvement from a naïve trial. We then adjusted the protocol to include a naïve trial and one to two trials between the naive and delayed trials, and we conducted sessions over 8 days. Young mice showed significant improvement across sessions between the naïve swim and all other trials only when there were 3 trials (including the naïve trial) before the delay trial and 8 days of testing. We then tested 3, 10, and 26 month old mice on this new protocol. The 3 month old mice again showed improvement between the naïve trial and all other trials. The 10 month old mice showed no significant improvement between the naïve swim and the two immediate trials, but did show significant improvement between the naïve trial and the delayed trial. The 26 month old mice showed no significant improvement from the naïve swim in any of the other trials, including the first immediate working memory trial and the delayed trial. The results of these studies showed that aging in C57Bl/6 mice was associated with declines in working memory performance in a spatial memory task. The old mice showed changes in both immediate and delayed memory, but immediate appeared to be affected at an earlier age.
Key words:
Aging, Morris water maze, prefrontal cortex, mice, spatial memory
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