Growing evidence indicates that ATP may play a very important role in Long-Term Potentiation (LTP), a neurophysiological process that has been implicated in memory formation. LTP is an enhancement of synaptic strength induced by a specific pattern of high frequency stimulation, or by application of exogenous ATP. In the hippocampus LTP-inducing stimulation is accompanied by a massive, Ca(2+)-dependent release of ATP from presynaptic terminals. Released extracellular ATP may either interact with numerous types of ATP receptors present on the neuronal surface, or serve as a substrate for ecto-protein phosphorylation. The results of combined electrophysiological and biochemical experiments indicate that participation of extracellular ATP in the ecto-protein phosphorylation process is most likely involved in the permanent amplification of the synaptic response in the hippocampus.