The experiments will investigate and compare in rats the physiological events and biochemical mechanisms that produce hippocampal long-term potentiation (LTP) and the increase in synaptic responses generated by the lateral olfactory tract (LOT) in piriform cortex following learning. Short (four pulse) bursts applied in a pattern that mimics the naturally occurring theta rhythm will be used in both lines of research. In hippocampus, patterned stimulation produces an LTP that is stable for weeks and is triggered in two stages: 1) a diffuse and very transient """"""""priming"""""""" event and 2) a """"""""consolidation"""""""" step that is restricted to the synapses activated by the repetitive stimulation. The proposed experiments will investigate the possibility that additional stages are present, characterize the physiological events occurring during each of these, and explore the chemical processes (elevation of calcium, stimulation of particular receptors, activation of specific enzymes) that lead to the lasting modification of synaptic efficacy. Patterned stimulation of the LOT will serve as a replacement for natural odors in a series of olfactory discrimination problems. The experiments will attempt to localize the site (e.g. synapses or dendritic trees) that are modified so as to produce the stable increase in the monosynaptic LOT-piriform response that occurs during learning of the simulated odors and explore the reasons that the stimulation does not produce this effect in the absence of learning. Additional studies will test if both learning and synaptic changes are blocked by antagonists of particular amino acid receptors and inhibitors of a calcium activated protease hypothesized to be involved in memory formation in telencephalic networks. Finally, biochemical tests will be made of the prediction that patterned stimulation and learning activate this enzyme.
