Modeling microcircuits of realistic hippocampal neurons

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DESCRIPTION (provided by applicant): This project is a collaborative research program between experimental a cellular neurophysiologist and applied mathematicians. The central aim of the project is to develop detailed computational models of microcircuits composed principal neurons and interneurons in the CA1 region hippocampus. In particular, these computational models will: 1) Be based on the latest data available from patch-clamp experiments dealing with ionic conductances, calcium and two-photon imaging, and cell morphology. 2) Use ionic channel models specifically designed to accurately reproduce the experimentally determined behavior. 3) Use full-cell morphologies; in particular, the same individual cells from which electrophysiology data have been taken will be digitized for the computational studies. 4) Develop new adaptive computational methods that can be used to speed up the computational simulations. A long-term goal of the project is to develop sufficiently accurate models of excitatory and inhibitory cell types in the hippocampus so that realistic simulations of small networks present in the hippocampus can be performed. These computational simulations are intended to be a tool to guide the development of new patch-clamp experiments that further explore the functional behavior of the hippocampal region. It is anticipated that the resulting studies will ultimately foster an improved understanding of how the hippocampal network stores and retrieves memories. Specific benefits of the proposed research and training objectives are: 1) New models will be developed of morphologically reconstructed neurons from which electrophysiological measurements have been obtained using multiple patch-clamp electrodes and/or calcium imaging. 2) New ionic conductance models will be constructed to accurately reproduce the experimental results. 3) New computational methods will be developed to speed up the compartmental model simulations. 4) New models will be developed to explore network interactions between excitatory and inhibitory neurons within the hippocampus. 5) Graduate students and postdoctoral researchers, recruited from the ranks of applied mathematicians interested in biological applications, will be trained in computational neuroscience.