Optogentic control of epileptic seizures in a network mapped by simultaneous calcium recordings and fMRI

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This project employs a novel and unique combination of optogenetics, fiber-based calcium recordings and functional magnetic resonance imaging (fMRI) to investigate neuronal networks in a rat model of human absence epilepsy, the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and to explore strategies for optogenetic interventions to interfere with epileptic seizures. Epilepsy affects more than half a million people in Germany, but the exact mechanisms of aberrant network activity in the brain remains elusive. Calcium recordings allow for seizure detection and in depth analysis and interpretation of simultaneously acquired fMRI data. Hemodynamic responses will be derived for specific brain regions and/or seizure phases. Even more, line scanning fMRI allows for read out of cortical layer-specific hemodynamic response functions. Based on accurate hemodynamic response functions, seizure maps with high spatial and temporal specificity will be derived revealing nodes of aberrant network activity and potentially essential, remote seizure choke points. Brain slice experiment at these choke points will systematically investigate and optimize optogenetic approaches, namely silencing of excitatory neurons or activating neurons, to interrupt seizures. Successful strategies will subsequently be transferred and applied in the in vivo model by simultaneous optogenetic-calcium recording-fMRI. Thus, a comprehensive assessment of both neuronal and hemodynamic activity of the epileptic network, including potential choke points at remote brain regions will become possible, and the most promising optogenetic approach to interfere with seizures will be identified.