Persistent protein kinase activation in the maintenance phase of long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a robust form of synaptic plasticity that may contribute to mammalian memory formation.A variety of pharmacological evidence suggests that persistent kinase activation contributes to the maintenance of LTP.To determine whether persistent activation of protein kinases was associated with the maintenance phase of LTP, protein kinase activity was measured in control and LTP samples using exogenous protein kinase substrates in an in vitro assay of homogenates of the CA1 region of rat hippocampal slices.After LTP, protein kinase activity was persistently increased, and the induction of this effect was blocked by the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid.The increased protein kinase activity was found to be significantly attenuated by PKC(le-se,, a selective peptide inhibitor of protein kinase C. Thus, LTP is associated with an N-methyl-D-aspartate receptor-mediated generation of a persistently activated form of protein kinase C.These data lend strong support to the model that persistent protein kinase activation contributes to the maintenance of LTP.Long-term potentiation (LTP)' is a well established form of neuronal plasticity manifest as an increased efficacy of transmission at specific synapses.The molecular mechanisms that underlie this process are not well characterized.Previous studies have suggested a role for protein kinase activity in the maintenance phase of LTP.It was reported that H-7, a nonspecific protein kinase inhibitor, could selectively block the maintenance of LTP (1, 2), suggesting that persistent activation of a protein kinase was necessary for maintenance of LTP.Other reports challenge this interpretation and suggest that H-7 nonspecifically affects normal physiological responses in control hippocampal slices in a manner similar to the effect on potentiated slices (3).