Vol. 4 nº 1 - Jan/Feb/Mar de 2010
Original Article Páginas: 23 a 27

Effects of intrahippocampal administration of the phosphatase inhibitor okadaic acid Dual effects on memory formation

Authors Monica R.M. Vianna1, Adriana Coitinho1, Luciana Izquierdo2, Ivan Izquierdo2

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keywords: hippocampus, PP1, PP2A, okadaic acid, short-term memory, long-term memory.

ABSTRACT:
Protein phosphorylation mediated by serine-threonine kinases in the hippocampus is crucial to the synaptic modifications believed to underlie memory formation. The role of phosphatases has been the focus of comparatively little study. Objectives: Here we evaluate the contribution of the serine-threonine protein phosphatases 1 and 2A (PP1, PP2A) on memory consolidation. Methods: We used immediate post-training bilateral hippocampal infusions of okadaic acid (OA, 0.01 and 10 pmol/side), a potent inhibitor of PP1 and PP2A, and measured short- [3 h] and long-term memory [24 h] (STM, LTM) of step-down inhibitory avoidance. Results: At the lower dose, OA inhibited both STM and LTM whereas at the higher dose it instead enhanced LTM. Pre-test infusion of these two doses of OA had no effect on retrieval. Conclusions: These two doses of OA are known to selectively inhibit PP1 and PP2A respectively. These findings point to the importance of these enzymes in memory formation and also suggest a deleterious influence of endogenous hippocampal PP2A on LTM formation.

 

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