Chronic recording studies of hippocampus in freely moving rats have identified patterns of neuronal activity that approximate electrical stimulation paradigms known to be very effective in inducing long-term potentiation (LTP). Given the considerable evidence linking LTP to memory, the observed naturally occurring patterns could be part of the process whereby information is encoded in brain networks. The proposed work will test if this hypothesis accounts for the amnestic effects of benzodiazepines, a class of drugs widely used for the treatment of anxiety. Thus, the experiments will ask if benzodiazepines disrupt three LTP-related physiological events and do so at dosages sufficient to impair encoding into long-term memory. The specific goals of the program are as follows: one, determine if the previously observed suppression of LTP by diazepam is due to the enhancing effect of the drug on inhibitory potentials; two, test if amnestic doses of diazepam are sufficient to block induction of LTP in intact rats; three, test if amnestic doses of diazepam block LTP-related patterns of neuronal activity in acute and/or chronic rats; four, compare relative potencies of different benzodiazepines on LTP-related events with their reported potencies on memory encoding; five, assess effects of different dosages of benzodiazepines on performance variables and the acquisition and retention of memory in an olfactory task. The data from these specific aims should make it feasible to test specific predictions, about dose- dependent relationships between the physiological and behavioral effects of benzodiazepines using chronic recording techniques. In general, the experiments will provide tests of hypothesized relationships between LTP and memory and should increase understanding of the amnestic effects of a clinically important class of drugs.
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