Abstract

The mesial temporal lobe epilepsy syndrome (MTLE) is the most common form of focal epilepsies. MTLE patients usually respond very little to pharmacological therapy and surgical resection of temporal brain areas is mandatory. Finding less invasive therapies than resection of the sclerotic hippocampus requires knowledge of the network structures and dynamics involved in seizure generation. Investigation of the time interval immediately preceding seizure onset would help in understanding the initiation mechanisms of the seizure proper and, thereby, possibly improve therapeutical options. Here, we employed the in vivo intrahippocampal kainate model in mice, which is characterized by unilateral histological changes, resembling hippocampal sclerosis observed in human MTLE, and recurrent focal seizures. In these epileptic mice, population spikes occurred during epileptiform events (EEs) in the ipsilateral, histologically changed hippocampus, but also concomitantly in the contralateral, intact hippocampus. We studied synchronization processes between the ipsilateral, sclerotic hippocampus and the contralateral hippocampus immediately preceding the onset of EEs. We show that coherence between the two hippocampi decreased consistently and reliably for all EEs at 8 to 12 s before their onset at high frequencies (> 100 Hz), without changes in power in these bands. This early decoupling of the two hippocampi indicates the time range for cellular and network mechanisms leading to increased excitability and/or synchronicity in the tissue and thus ultimately to epileptic seizures.

Corresponding author. Bernstein Center for Computational Neuroscience Hansastr. 9A, 79104 Freiburg i.Br., Germany. Fax: +49 761 203 9559.
¹ Both authors contributed equally to this work.