Computational Analysis of Hippocampal Function

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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. Place cells of the hippocampus are an ideal system to study these issues. These cells fire robustly and specifically in restricted locations in an environment. They are thought to encode a spatial framework used to organize the items and events of experience, forming the foundation of episodic memory and flexible, context-dependent learning. A major advance in the study of these cells has been the development of techniques to record the activity of dozens of well-isolated neurons simultaneously from different parts of the hippocampal formation. These techniques provide experimenters the tools to test influential computational theories of hippocampal function that have existed for decades without rigorous testing at the level of single-unit physiology. We propose to develop a computational model of processing in the hippocampal formation to aid in the analysis and interpretation of ensemble unit recording from our laboratory. The goal is to understand the mechanisms that transform the input properties at each level into the output properties, and to deduce functional roles from these mechanisms. To this end, it will be necessary to implement computer simulations of the response properties, in order to engender insights into the data that would not arise from less formal analysis; to stimulate additional analysis of the data that would not have otherwise been conceived; and to inspire new experiments to address issues and hypotheses that result from the computational analyses. These analyses will investigate (1) the role of global inhibitory mechanisms in the remapping of place fields, (2) the role of recurrent collateral circuitry in the dynamic responses of place fields to controlled environmental manipulations, and (3) the role of neural plasticity, in particular spike-timing dependent plasticity, in the dynamic responses of place cells to controlled environmental 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 studies will generate 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.