Rapid post-translational modification of brain phosphoprotein may mediate the rapid onset of synaptic modifications that underlie synaptic plasticity. The phenomenon of long-term potentiation (LTP) involves a rapid dramatic change in synaptic activation which is persistent for days or even months. Because of its relation to models of information storage and memory we have studied the effect of LTP on special identificable brain phosphoproteins, to determine their particular role in LTP. By using different methods to preserve that in vivo state of these proteins, it is possible to show that LTP increases the state of phosphorylation of a specific protein, protein F1 (molecular weight 47,000; isoelectric point, 4.5) and that this increase is due to the activation of a specific enzyme, protein kinase C.) We now propose to micro-inject chemical agents that can stimulate protein kinase C or inhibit its action to establish whether this enzyme is both necessary and sufficient for synaptic plasticity. Because LTP can be controlled, both with regard to extent and time course (up to 3 months in long term studies) the time frame for protein kinase C participation in LTP can be identified. The identification of protein F1 and protein kinase C important for regulating information flow and registration in the central nervous system may provide new insights into diseases of memory such as presenile dementia of the Alzheimer's type.
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