Esther Flores, Biomicrotechnology, IMTEK: Combining Microelectrode Arrays, Patch clamp and Calcium Imaging for understanding the integration of the synaptic input in cultured networks

Abstract

Hypersynchronous network activity is the defining hallmark of epilepsy and manifests in a wide spectrum of phenomena of which electrographic activity during seizures is only one extreme. We developed a framework to differentiate between types of epileptiform activity patterns and investigated their temporal interactions. In local field potentials of freely behaving epileptic mice, epileptiform spikes occur in distinct bursts. We derived a scale reflecting the spike load of bursts and three main burst categories: high-load, medium-load and low-load bursts. These different burst types are non-randomly distributed in time: High-load bursts form clusters and are typically surrounded by transition phases with increased rates of medium-load and low-load bursts. In apparent contradiction to this, increased rates of low-load bursts were positively correlated with the duration of phases lacking high-load dynamics. These findings are consistent with the hypothesis that low-level epileptiform activity can promote network stability in epilepsy, but that its impact ultimately depends on the current state of the network. We further found that the rate of high-load bursts correlates with early and late anatomical as well as behavioral markers of epilepsy. This corroborates the validity of our approach and suggests that high-load bursts can be used to diagnose the severity of epilepsy.

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