The general goal of the proposed work under this Research Scientist Award is to identify the cellular events that allow humans and other mammals to rapidly and stably encode large amounts of information as a routine part of life. Progress in this effort should significantly increase our understanding of many aspects of both normal and abnormal behavior. The first three projects deal with the long-term potentiation (LTP) effect. LTP is a physiologically induced increase in synaptic strength that has several properties expected of a memory substrate; experimental studies have also linked the phenomenon to certain types of memory. Project one will test the hypothesis that the production of stable LTP involves a locally derived trophic factor (platelet activating factor) which augments the activity of a calcium dependent protease (calpain). Project two addresses the synaptic modifications responsible for the enhanced physiological responses that define LTP. The proposed studies will repeat and extend recent pharmacological work pointing to a change in the conductance properties of a subclass of transmitter receptors as the event which expresses the potentiation effect. Project three is concerned with how LTP is maintained for weeks or longer. The proposed experiments will test the hypothesis that a specific class of adhesion receptors (integrins) is concentrated in synaptic membranes and serves to anchor synapses in a potentiated static. The final group of proposed studies (Project four) explores a type of plasticity quite different than LTP that could potentially play an important role in the operation of the memory system. Tests will be made to determine if repetitive synaptic activity occurring over days affects the levels of myna encoding for the transmitter receptors (i.e., the AMA subclass of glutamate receptors) found in hippocampus and cortex.
