Reverse Engineering Cortical Circuitry

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DESCRIPTION (provided by applicant): The subiculum is a crossroads of hippocampal and parahippocampal projections, and the major output structure of the region. The subiculum is a region of intermediate complexity between CA3, a region with a single layer of interconnected pyramidal neurons, and the 6-layered parahippocampal and neocortices, regions with multiple principal cells connected via intralaminar and interlaminar circuits. Physiological investigation and modeling of CA3 has provided many insights into basic epileptogenesis. The greater complexity and location of subiculum makes it a logical next structure for study of additional mechanisms of seizure origin and spread. We propose to evaluate connectivity and activity spread in subiculum by combining anatomical and physiological methods with computer modeling. We will focus on network dynamics, using existing results to define voltage-sensitive and synaptic channels for the cell models. The research will proceed via the following specific aims: AIM 1: Measure subthreshold and suprathreshold properties of pyramidal and interneurons of subiculum and relate these to firing patterns and dendritic morphology. AIM 2: Develop combined and hybrid neural network software tools and fitting algorithms to match models to physiology. AIM 3: Define input/output relations for subicular pyramidal cells to excitatory and inhibitory connections. AIM 4: Explore spread of activity with multi-electrode recordings and match patterns of spread to the computer network model. Our research will allow us to begin to define and classify patterns of activity initiation, filtering, sustention and boosting in cortical circuits. This will set the stage for use of the subiculum slice and subiculum computer model as an epilepsy model.