An in vitro model of persistent epileptiform activity in neocortex

An in vitro model of persistent epileptiform activity was developed to study the mechanisms involved in epileptogenesis. Extracellular recordings were obtained from rat neocortical slices exposed to magnesium-free solution for 2 h. During exposure to magnesium-free solution spontaneous epileptiform activity consisting of interictal bursting and ictal-like discharges were observed. Interestingly, this activity persisted for hours after the slices were returned to magnesium-containing control solution. The N-methyl-D-aspartate (NMDA) receptor antagonist CPP prevented the development of the epileptiform activity, while the non-NMDA receptor antagonist CNQX abolished the epileptiform discharge that persisted after slices were returned to control solution. These findings suggest there are two distinct phases in the development of epileptic activity in this model, namely, induction (mediated by NMDA receptor activity) and maintenance (supported largely by non-NMDA receptor activity). The similarities and possible parallels between the mechanisms underlying this epileptogenesis and other forms of use-dependent modification of synaptic excitation, such as long-term potentiation, are discussed. This in vitro model of neocortical epileptogenesis may provide insights into the events underlying the development of clinical partial epilepsy.