This research program is directed towards an understanding of the electrophysiological, neurochemical and behavioral correlates of the decline in spatial cognition and memory with age. The ultimate goal is the development of preventative or ameliorative treatments for this decline in mental health. The investigations focus on aging of the rodent hippocampal system, including its intrinsic connections and information processing neural structures make to cognitive changes that occur in old age. There are three main experimental questions addressed in this proposal, and five aims for professional growth. The first experimental question concerns the degree to which the age- related loss of spatial selectivity in hippocampal unit activity that we have found might be accounted for by disruption in information processing characteristics of its cortical afferents, and what the consequence of this loss might be for information processing at neural levels receiving hippocampal output. This problem will be addressed using a new techniques developed in this laboratory (the stereotrode) that enables the simultaneous recording from several single neurons in conscious animals moving freely in a spatially extended environment. The second major question is whether information storage throughout the lifespan results in a significant rearrangement int he statistical distribution of connection strengths in old neurons, which might account for the restriction in the range of behavioral adaptability of older animals. The answer to this question requires the analysis of cellular interactions at the level of single neurons rather than the population techniques as employed in previous studies. The third major experimental question concerns the possibility that modulatory influences in the hippocampus from subcortical afferent systems change with age, and contribute to the observed cognitive deficits. This question will be addressed using local electrical and chemical excitation or reversible chemical inactivation of discrete subcortical projection nuclei in conscious young and old animals.
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