From Microscopic to Macroscopic – Mechanisms Underlying Epileptic Seizures

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There are a wide variety of neuronal dynamics that are classified as seizures. We pose the hypothesis that, as in any description of the physics of ensembles, the macroscopic phenomena of a seizure needs to be characterized in terms of the interactions between the relevant neuronal subtypes taking part in this process. As in non-biological pattern formation processes, persistently activity states, such as persistent turbulence, may depend critically on the interplay between fundamental modes of activity. In neuronal systems, such modal interactions must take into account inhibitory (interneurons) and excitatory (principal cells) elements. We discuss the characteristics of synchronization between interneurons and pyramidal cells in hippocampal seizures, using multiple intracellular recordings from pairs and triples of cells. We describe how interneuron depolarization block may be an integral component in orchestrating the time course of seizures, and how gap junction connectivity may synchronize such depolarization block among interneurons. We contrast these findings with the synchronization characteristics from human seizures. Lastly, we discuss how the coupling of network instability to ion shifts appears critical in sculpting network dynamics as seizures evolve. Searching for the universality that might underlie the variety of seizure dynamics in human epilepsy remains an important open challenge.