Changes in protein kinase C (PKC) activity,isozyme translocation,and GAP-43 phosphorylation in the rat hippocampal formation after a single-trial contextual fear conditioning paradigm

The hippocampus plays an important role in spatial learning and memory. However, the biochemical alterations that subserve this function remain to be fully elucidated. In this study, rats were subjected to a single-trial contextual fear conditioning (CFC) paradigm; the activation of different protein kinase C (PKC) subtypes and the levels and phosphorylation of the plasticity-associated protein GAP-43 were assayed in the hippocampus at varying times after training. We observed a rapid activation of hippocampal PKC (15 min through 24 h), with differential translocation of the PKC isotypes studied. At early times after CFC (15-90 min), PKCalpha and PKCgamma translocated to the membrane, while PKCbetaII and PKCepsilon moved more transiently (15 to 30 min) to the cytosol. These PKC isotypes returned to the membrane at later time points after CFC. Correlating with these changes in PKC translocation and activity, there was an early decrease in GAP-43 phosphorylation followed by a more sustained increase from 1.5-72 h. GAP-43 protein levels were also increased after 3 h, and these levels remained elevated for at least 72 h. These changes in PKC and GAP-43 were specific to the CFC trained animals and no changes were seen in animals exposed to the same stimuli in a non-associative fashion. Comparison of translocation of different PKC isotypes with the changes in GAP-43 phosphorylation suggested that PKCbetaII and PKCepsilon may mediate both the early changes in the phosphorylation of this protein and the increases in GAP-43 expression at later times after CFC.