EFFECTS OF AGING ON SPATIAL-LEARNING AND HIPPOCAMPAL PROTEIN-KINASE-CIN MICE

C57BL/6Nia and F1(B6xD2)Nia mice were tested on the Morris water maze task for 5 days followed by 12 days of testing on the place learning-s et task (8 trials/day with each task). Mice were tested at 3, 14, and 25 months of age. C57 mice, 25 months of age, were significantly impai red in both the Morris and place learning-set task probe trial perform ance compared to mice 3 months of age (p < 0.05). These aged C57 mice also demonstrated a significant reduction in membrane-bound hippocampa l protein kinase C (PKC) activity (p < 0.05) with no significant chang e in cytosolic PKC activity. F1 mice, however, showed no effect of age on probe trial performance on the spatial learning tasks. In addition , in a comparison of C57 and F1 mice within each age group, F1 mice de monstrated superior learning performance which was accompanied by a si gnificant elevation in PKC activity (p < 0.05). Spatial learning perfo rmance of both strains significantly con-elated with membrane-bound PK C activity (p < 0.01). These data provide additional support for our p revious hypothesis of an involvement of hippocampal PKC activity in sp atial learning and suggest that the amount of membrane-bound PKC activ ity may be a determinant of age-related decline in spatial learning.