MULTI-SITE ANALYSIS OF HIPPOCAMPAL NEURONAL ENSEMBLES

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A major goal of cognitive neuroscience is to understand behavior and mental processes in terms of the physiological properties of neural circuits. Spatial learning is a prominent paradigm for studying these issues. Mammalian brains encode a cognitive map of the environment, which is used to remember and navigate to important locations. Place cells of the hippocampus, which fire in restricted locations in space, are thought to constitute this cognitive map. The goal of this research program is to understand how place cells and neurons in related areas interact to generate the spatially specific firing of these neurons. The role of hippocampus in learning and memory has been modeled as an associative network with two important properties: pattern completion, the ability to retrieve a stored pattern from degraded input, and pattern separation, the ability to make stored representations of similar inputs more dissimilar. Theoretical and experimental studies hypothesize that (1) the dentate gyrus performs pattern separation; (2) CA3 performs pattern completion; (3) CA1 compares the CA3 output with entorhinal cortex; and (4) the subiculum encodes a universal map for path integration. Powerful, new multi-electrode technology will be used to record dozens of neurons simultaneously for these brain areas to test these hypotheses. These recordings will allow within-animal comparisons of the changes induced in the spatial maps encoded by each area as a result of experimental manipulations. It is hypothesized that (1) dentate gyrus will "remap" an environment in a graded fashion; (2) CA3 will be unaffected by small environmental changes but will form new representations for large changes; (3) CA1 will also be unaffected by small changes, but will tend to remap large changes only partially; and (4) subiculum will be unaffected by these manipulations. The devastating neurological effects of such diseases as Alzheimer's Disease and epilepsy are intimately tied to dysfunctions of the hippocampus and related brain areas. These experiments will generated fundamental insights into the neural interactions between these brain areas that underlie learning and memory, as well as insights into how these mechanisms go awry in these debilitating diseases.