Long-term potentiation induction - A synaptic catch mechanism released by extracellular phosphorylation

The best understood form of long-term potentiation in hippocampal CAI neurons is induced by activation of the N-methyl-D-aspartate receptor complex and subsequent activation of the intracellular second messenger systems. Tn addition to this intracellular mechanism, long-term potentiation can also be induced by an extracellular mechanism involving phosphorylation by ATP-ecto-protein kinase. In the present study, we hypothesize that a putative blocking molecule of the formation of long-term potentiation exists on the synaptic membrane, and examine whether ecto-protein kinases play a role in the block of long-term potentiation by phosphorylating the ecto-domains of this molecule in CA1 neurons of guinea-pig hippocampal slices. Long-term potentiation was induced by theta burst stimulation whether or not the test input was delivered to the CA1 neurons following burst stimulation. However, 5 mu M K-252b, an ecto-protein kinase inhibitor, only blocked the induction of long-term potentiation when the test input was delivered during a 30-min period following burst stimulation. The results suggest that the process of formation of long-term potentiation continues independently of test synaptic input, while the block of long-term potentiation results from a combination of an interruption of the ATP-ecto-protein kinase-dependent processes and continued test synaptic input after burst stimulation. This block of long-term potentiation, which should be released by activation of ATP-ecto-protein kinase, is suggested to act as a "safety catch" for synaptic plasticity in hippocampal CA1 neurons. (C) 2000 IBRO. Published by Elsevier Science Ltd.