Cellular and molecular mechanisms underlying aberrant network reorganization in the epileptic brain

Abstract

Well-refined wiring of neural circuits is fundamental to proper brain function. Aberrantly formed neural circuits may induce epileptiform discharges of neurons. Therefore, elucidating the cellular and molecular mechanisms that underlie the development of aberrant neural circuitry will advance the understanding and prevention of epilepsy. The dentate gyrus has been suggested to serve as a gate that prevents the propagation of epileptiform activity from the entorhinal cortex to the hippocampus. Within the dentate gyrus is the dentate granule cell layer, which consists of densely packed granule cells that maintain intrinsically low-firing properties and rarely exhibit burst discharges synchronized with other neurons. Additionally, granule cells form abundant synaptic inputs to inhibitory interneurons in the dentate hilus, a fraction of which provide feedback inhibition back to the granule cells. Network reorganization of the dentate gyrus in patients with temporal lobe epilepsy and in corresponding animal models was reported. Specifically, mossy fiber sprouting and the emergence of ectopic granule cells contribute to the observed phenotypes. This paper reviews the expanding literature on the cellular and molecular mechanisms underlying the formation of aberrant hippocampal networks and their role in epileptogenesis.