Estorgen Effects on Place Cells and Navigation Strategy

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This proposal examines estrogen effects on strategy use during spatial navigation and on hippocampal (HPC) representations of space. Estrogen (E) has been found to cause structural changes in CA1 pyramidal cells during the proestrus phase of the estrous cycle and during E treatment. Therefore, it is hypothesized that E in the HPC will result in changes in pyramidal cell electrophysiological properties, biasing the spatial navigation system for differential strategy use during high and low E conditions. To test this, spontaneous strategy use in a T-maze will be compared within animals across the estrous cycle, and between ovariectomized (OVX) and recorded and OVX with E replacement animals. Once differences in strategy use are detected, HPC CA1 place cells will be recorded while rats run on T-maze in a cue-enriched environment. Comparisons of place cell properties will initially be made between OVX and OVX+E animals and subsequently across an animal's estrous cycle. To test the stability of place cells, place field size and reliability, and responses to scrambled and novel cues are expected. This study seeks to contribute novel information on behavioral learning and memory correlates of the well-documented phenomenon of E-induced structural changes in HPC, and to provide initial data on how E affects neural representations of space in the HPC. This study has clinical relevance to the study of memory and cognitive changes associated with E loss in post-menopausal and aging women.