Alpha calcium and calmoduline-dependent kinase II (CaMKII) is the major protein in glutamateric neurons in the forebrain. Its activity is regulated by autophosphorylation on the threonine 286. CaMKII-T286A mutant mice have severe defi cits in context memory formation. They form fear memory of the context in fear conditioning task only after very intensive training with 5 shocks. Here we present the data showing that foreground fear conditioning training does not induce expression of any of the analysed immediate early genes (c-Fos, Zif268, Nur77 or JunB) in CaMKII-T286A mutant mice. Furthermore, long-term fear memory in the mutants cannot be blocked by administration of mRNA or protein synthesis inhibitors (actinomycin D or anisomycin) into dorsal hippocampus. Moreover, as revealed by Illumina microarrays, fear memory training does not induce context-shock association specifi c expression in the hippocampus. On the other hand, the training of the CaMKII-T286A mutant mice induces in the hippocampus expression of locally-translated proteins, Arc and PSD-95. In addition, both training-induced PSD-95 expression and long-term fear memory can be blocked by intrahippocampal administration of rapamycin (inhibitor of mammalian target of rapamycin kinase, the main regulator of local translation). Thus, our data strengthen the notion that local translation of PSD-95 in the dorsal hippocampus is the mechanism of long-term memory formation in the absence of alpha CaMKII autophosphorylation.
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