Throughout our investigation of the mechanisms underlying hippocampal memory replay, we will employ a strategy of continuous interaction between experimental and modeling approaches. First, we consider conceptual models, and formulate hypotheses relevant to the initiation, generation and termination of SPW-Rs. Then, as we gather critical new experimental data to test those hypotheses in Projects 1-4, we will use that data to constrain full-scale biophysically-detailed computational models of hippocampal networks, integrating a newly developed model of CA3 with existing models of dentate gyrus (DG) and CA1. These models will then be used to predict the complex responses of the network to simulated perturbations, help interpret experimental outcomes, inform hypotheses about underlying principles, and suggest new experiments to test those hypotheses. In addition to an improved conceptual understanding of memory replay, our final product will include full-scale network models of the hippocampus with unprecedented functionality, fully open-sourced and freely available to the broader neuroscience community. !
