Rapid post-translational modification of brain phosphoproteins 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 propose to suty the effect of LTP on specific identifiable brain phosphoproteins, to determine their particular role in LTP. We propose to study those phosphoproteins whose identity or regulators is known, but whose role in synaptic modification is not. By using different methods to preserve the in vivo state of these proteins, it is possible to determine whether LTP increases or decreases the state of phosphorylation of a specific protein. Because LTP can be controlled, both with regard to extent and time course (up to 3 months in long term studies) phosphoprotein metabolism important for LTP can be identified. The identification of those proteins 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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