The research proposal is a resubmission of a grant that was reviewed in June, 1998. The proposed research will investigate hippocampal electrophysiology in young and old rats in three experiments examining hippocampal sensitivity to disruption, the relationship between place field stability and spatial memory performance, and the relationship between these and long-term potentiation mechanisms.The first experiment is designed to test whether or not the old hippocampus is near threshold for retrieval failure due to loss of synapses and synaptic plasticity. The PI will record groups of cells in the right hippocampus before and after the rats' left hippocampus is injected with lidocaine via indwelling cannula. The rats will seek electrical brain stimulation reward in two similar chambers during the recording sessions. The hypothesis predicts that older rats will be more sensitive to the unilateral hippocampal inactivation, and that both memory performance and hippocampal representations will be less consistent in older rats than younger rats.The second experiment is designed to determine if instabilities in hippocampal firing fields correlate with memory performance errors. The PI will record groups of hippocampal cells in young and old rats trained to operate an RCV--a rat controlled vehicle. The RCV apparatus allows the independent experimental control of the rat's movement, and its vestibular and visual experience. Trials will include both experimenter and rat-controlled movements with respect to locations and rewarded goal locations. The task for the rat will be to press a lever to control the movement of a mechanical arm to approach a goal. Old animals are expected to have poorer goal targeting with respect to the distal cues in the apparatus compared to young rats. Specifically, the changes in the location of a (group of) cell's place field(s) with respect to visual cues is expected to predict the rat's errors in finding goals.The third experiment will test the extent two which placefield properties involve NMDA receptor dependent plasticity and AMPA receptor associated ion currents. Young rats will be given NMDA receptor antagonists and several experience-dependent changes in place fields will be assessed. Old rats will be given drugs that increase AMPA currents. Hippocampal cell activity in both groups of rats will be assessed in a circular track and during sleep. NMDA receptor antagonists are expected to prevent experience-dependent place field changes in the young rats, and AMPA current enhancers are expected to ameliorate place field properties in the old rats.
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