Network Dynamics during Development of Pharmacologically Induced Epileptic Seizures in RatsIn Vivo

Abstract

In epilepsy, the cortical network fluctuates between the asymptomatic interictal state and the symptomatic ictal state of seizures. Despite their importance, the network dynamics responsible for the transition between the interictal and ictal states are largely unknown. Here we used multielectrode single-unit recordings from the hippocampus to investigate the network dynamics during the development of seizures evoked by various chemoconvulsants in vivo. In these experiments, we detected a typical network dynamics signature that preceded seizure initiation. The preictal state preceding pilocarpine-, kainate-, and picrotoxin-induced seizures was characterized by biphasic network dynamics composed of an early desynchronization phase in which the tendency of neurons to fire correlated action potentials decreased, followed by a late resynchronization phase in which the activity and synchronization of the network gradually increased. This biphasic network dynamics preceded the initiation both of the initial seizure and of recurrent spontaneous seizures that followed. During seizures, firing of individual neurons and interneuronal synchronization further increased. These findings advance our understanding of the network dynamics leading to seizure initiation and may in future help in the development of novel seizure prediction algorithms.