THE IMPAIRMENT OF LONG-TERM-MEMORY FORMATION BY THE PHOSPHATASE INHIBITOR OKADAIC ACID

While there is considerable evidence that protein kinase activity is i nvolved in memory formation, there has been, as yet, no direct investi gation of a role for protein phosphatases. However, phosphatases have been implicated in the effects of the activation of glutamate receptor s of the NMDA type, in longterm depression, and in the regulation of t ransmitter release and membrane ion channel activities, phenomena whic h have been shown to be possibly involved in cellular memorial process es. In the present paper, inhibition of protein phosphatase by 0.5 nM okadaic acid, a selective inhibitor of phosphatases 1 and 2A, is demon strated to prevent memory consolidation in day-old chicks trained on a single trial passive avoidance task. Retention losses first occurred after 30 min post-learning, at an intermediate stage of memory formati on preceding a protein synthesis-dependent long-term stage. It is sugg ested that protein phosphatase activity is involved in precursor proce sses to long-term memory consolidation.