Dentate circuitry as a model to study epileptogenesis

Abstract

Epileptogenesis, which can be initiated by brain insults or gene mutations in the normal brain, is defined as the gradual (months to years) process of epilepsy development that begins before the first epileptic seizure. Epileptogenic changes include induction of immediate early genes, post-translational modification of ion-channel functions, neuronal death, gliosis, and reorganization of neural circuits. Each of these changes alone or in combination can contribute to an epileptogenic focus, which is defined by the minimal cortical region that is necessary and sufficient to induce synchronized epileptic bursting activity in neurons. Therefore to discover and develop anti-epileptogenic drugs it is essential to unveil the cellular and molecular mechanisms underlying the development of epileptogenic foci. Among the epileptogenic changes, abnormally appended excitatory recurrent circuits can directly cause synchronized bursting of neuron activity. Here, I will introduce and discuss the mechanisms underlying the development of two representative abnormal neural circuits, namely, hippocampal mossy fiber sprouting and ectopic granule cells, which are found in the dentate gyrus of patients with mesial temporal lobe epilepsy and its animal models.