Postsynaptic long-term potentiation (pLTP) in the frog sympathetic ganglion will be used as a model system for the study of mechanisms of information storage in the nervous system. Previous work by others has demonstrated that pLTP occurs in the cell body of ganglion cells, that pLTP lasts for at least several hours, and that external Ca is required for induction. The initial goals of this proposal are to further described the phenomenon: the full time course of pLTP ill be characterized; voltage-clamp methods will be use to determine whether the conductance that is potentiated is the nicotinic ACh conductance, as previously concluded by others on the basis of current-clamp recordings. In a second set of experiments, Ca buffers and Ca itself will be injected intracellularly to determine whether a rise in Ca is necessary and sufficient for induction of pLTP. The third set of experiments is aimed at identifying the biochemical process responsible for the long duration of pLTP. The PI has proposed the theory that the Ca-calmodulin dependent protein kinase II has the requisite biochemical properties to be switched """"""""on"""""""" by a rise in Ca and to maintain this """"""""on"""""""" state long after Ca returns to baseline. The possibility that such a storage process is responsible for maintenance of pLTP will be tested using both biochemical and physiological methods. A monoclonal antibody that inhibits the function of this kinase will be injected to see if pLTP can be blocked. The kinase itself will be injected to see if pLTP can be induced. Biochemical assays will be used to determine whether the activity of this enzyme is turned """"""""on"""""""" during induction of pLTP and whether it remains """"""""on"""""""" for the duration of pLTP. Parallel studies on other kinases of interest will also be conducted. These studies will provide the first systematic test of the most explicit model of neuronal information storage yet proposed. The information acquired may well be relevant to the general questions of memory storage.
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