SPATIAL-LEARNING AND MEMORY IN CALPASTATIN-DEFICIENT RATS

The present experiments were concerned with the examination of the hyp othesis that a deficiency in calpastatin, the endogenous inhibitor of calpain, enhances learning and memory performance. In the first experi ment we used rats with an altered calpain/calpastatin balance (Milan h ypertensive strain, MI-IS, low calpastatin) to investigate the learnin g and memory of a spatial task in the Morris water maze in comparison with control rats with a normal calpain/calpastatin balance (Milan nor motensive strain, MNS). Since the two strains also differ in blood pre ssure, a third strain of rats was included to assess the role of hyper tension (spontaneously hypertensive rats, SHR). Although the acquisiti on rate of the spatial task was better in the low-calpastatin MI-IS ra ts than in their normal-calpastatin MNS controls, their performance wa s similar to that of the SHR rats, thus thwarting the conclusion that differences were due to the low level of calpastatin. The availability of another mutant strain, low-calpastatin level and normotensive (MH. NE), allowed a further examination of the hypothesis. In the second ex periment rats of the MH.NE strain acquired the spatial task as well as their normotensive controls, but their memory retrieval was clearly l ess than that of their normal-calpastatin controls. This deficiency wa s not due to impaired visual function or a slower swimming speed. The conclusion is that an inbalanced calpain/calpastatin ratio, although f avoring calpain activity, is disadvantageous for remembering a spatial task. This disadvantage is clearly overruled when this inbalance is a ccompanied by hypertension. (C) 1996 Academic Press, Inc.