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High frequency stimulation of fiber systems in the mammalian hippocampus produces a semipermanent increase in synaptic efficacy. This effect, long-term potentiation (LTP), has been of considerable interest as a potential substrate of memory due to its rapid onset and extreme persistence. Experiments are described that indicate that the locus of LTP is confined to the synaptic complex of the fibers stimulated; further, Ca2+ is shown to be essential for the initiation of LTP and may play a role in triggering this increase in synaptic efficiency. Data from biochemical analyses of LTP indicate that a 40,000 dalton synaptic membrane protein shows a highly reliable change in its endogenous phosphorylation following high frequency hippocampal stimulation. Phosphorylase kinase, a Ca2+ sensitive enzyme, is shown to specifically catalyse the phosphorylation of this 40,000 dalton protein. The data are discussed in terms of a working model in which the Ca2+ dependent phosphorylation of the 40,000 dalton protein produced by high frequency stimulation is a biochemical intermediate in the production of LTP.

Type

Journal article

Journal

Fed Proc

Publication Date

06/1979

Volume

38

Pages

2117 - 2122

Keywords

Animals, Calcium, Electric Conductivity, Hippocampus, In Vitro Techniques, Membrane Proteins, Memory, Nerve Tissue Proteins, Neurotransmitter Agents, Phosphorylation, Protein Kinases, Synapses, Synaptic Membranes, Time Factors