Microcircuits in Epilepsy: Heterogeneity and Hub Cells in Network Synchronization

Epilepsy is a complex disorder involving neurological alterations that lead to the pathological development of spontaneous, recurrent seizures. For decades, seizures were thought to be largely repetitive, and had been examined at the macrocircuit level using electrophysiological recordings. However, research mapping the dynamics of large neuronal populations has revealed that seizures are not simply recurrent bursts of hypersynchrony. Instead, it is becoming clear that seizures involve a complex interplay of different neurons and circuits. Herein, we will review studies examining microcircuit changes that may underlie network hyperexcitability, discussing observations from network theory, computational modeling, and optogenetics. We will delve into the idea of hub cells as pathological centers for seizure activity, and will explore optogenetics as a novel avenue to target and treat pathological circuits. Finally, we will conclude with a discussion on future directions in the field.