SPATIAL MEMORY AND HIPPOCAMPAL ANATOMY: NATURAL PATTERN

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The organization and function of the brain are of profound importance to the health sciences. One of the best studied brain structures is the hippocampus, and yet many questions remain about its role in cognitive processing. The present application proposes to study this question with a new approach. First, we will quantify natural variation in the learning ability of wild rodents in tasks known to require the hippocampus (spatial learning). Second, we will qualify anatomical measures that are correlated with learning ability in laboratory mice: the relative volume of different hippocampal components. Third, we will measure the same behaviors and the same hippocampal components in the lab-reared offspring of these wild rodents, so that we may estimate the impact of experience on learning and hippocampal proportions. Finally, our subjects will be two closely-related rodent species whose spatial behavior diverges in a remarkable manner: in one species, males learn faster than females, in the other there is no sex difference. The experimental groups (two sexes from each of two species, reared under each of two conditions) will first be tested on a series of spatial learning paradigms. We predict that differences between groups will be correlated to natural differences ranging behavior and experimental manipulations of spatial experience. We will then measure the volume of hippocampus in each subject; particularly those components known to vary with spatial performance. To make these measurements, sectioned brain tissue will be stained using the Timm's sulphide-silver method for visualization of hippocampal components. We will then use an image-processing workstation to measure and calculate ratios of "within" hippocampus measure (mossy fiber projection to regio inferior, CA1 to entire hippocampus), and measures of hippocampal volume relative to gross measurements (telencephalic volume, brain weight, body weight, hind foot length). Again, we predict that differences between groups will be correlated to known species differences and to differences in space use during rearing. Natural variation in sex-specific leaning patterns provides a novel window into cognitive function. By linking this perspective with existing data on space use in the wild, and new data on spatial learning and the relative size of the relevant brain structures, we hope to shed new light on the evolution of cognition itself.