The general aim of this project is to characterize age-related alterations in learning and memory capacity and associated changes in neural coding by hippocampal/cortical systems presumed to underlie the cognitive decline. Previous work from this laboratory and elsewhere indicates that the hippocampal system mediates declarative memory and that hippocampal processing central declarative memory is reflected in neuronal activity dependent on conjunctions and/or relations among critical cues in different behavioral paradigms. The proposed experiments are aimed at testing the specific hypothesis that age- related cognitive decline is attributable to a disproportionate deterioration of declarative memory and corresponding loss of conjunctional-relational correlates of hippocampal unit activity, disruption of cortic-limbic coordination, and reduced induction or rapid decay of learning related plasticity in hippocampus and cortex. In a series of empirical studies we propose to test this hypothesis by assessing the behavioral performance of young adult and ages rats in four odor- and spatially-guided learning tasks that impose different kinds of demands on hippocampal processing. We will also characterize the behavioral correlates of single neurons, the relationship between sensory and hippocampal rhythms, and synaptic efficacy of hippocampal and cortical circuitry in rats performing those tasks. Our analyses will focus on comparisons of the data from behaviorally """"""""impaired"""""""" and """"""""unimpaired"""""""" old rats with that from young mature adults. In parallel computational modeling studies, we propose to develop multiple network models that stimulate hippocampal neural activity and examine the effects of analogues of age-related circuitry changes on processing performance. Our initial studies will compare the effects of aging-like alterations on the processing performance of several simplified models of hippocampal networks. Further studies will involve the development and assessment of the effects of these alterations in more realistic hippocampal models. Our goal is to build models of the hippocampus that stimulate, and therefore can be validated by, the data from recording studies. We will assess the effects of both individual changes that occur in aging and combinations of them to identify the critical determinants of cognitive decline.
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