Abstracts

Rationale: Epileptogenesis is a dynamic process involving several molecular and cellular mechanisms that support the rearrangement of neuronal networks which foster the onset of recurrent seizures. High frequency oscillations (HFOs) described in the brain of epileptic animals and patients with epileptic disorders have been postulated as a predictive marker of epileptogenesis. Since HFOs represent hypersynchornized action potentials of small neuronal networks, other abnormal electrical patterns should be studied and characterized to further understand their role in epilepsy.The goal was to simultaneously characterize spontaneous neuronal oscillatory expression patterns within different hippocampal regions during epileptogenesis. Methods: An experimental model of temporal lobe epilepsy was induced by intraperitoneal administration of kainic acid or pilocarpine in adult mice and rats. Following recovery from status epilepticus (SE), silicone probes with a 16 parallel microelectrode array were implanted in the dorsal hippocampus parallel to the CA1-dentate gyrus axis. Local field potentials from the hippocampus were recorded after being amplified, band-pass filtered (1 Hz-3 kHz) and digitalized with 12 bit resolution at continuous 50 kHz through pre-amplified headstage and system data acquisition systems. Time-dependent changes of the oscillatory activity after SE were analyzed and compared with na ve animals. Analysis included: (1) quantifying bursts of HFOs and high voltage interictal spikes (IS), (2) frequency band analysis, and (3) characterizing depth voltage and spike units train profiles, (3) microseizure (microdischarges with repetitive and evolving patterns). Video monitoring and Racine s score were used to detect spontaneous seizures and quantify seizure severity, respectively. Results: As expected, HFO events were found in CA1 and DG regions during sleep-wake transition cycles of animals with clinical spontaneous seizures. HFOs modified the frequency of the subsequent local field potential activity. Microseizures were observed in different hippocampal layers. Most IS had a slow positive component and were located in the stratum oriens-pyramidal layers. Meanwhile, IS within the pyramidal layer and DG had high frequencies and reverse phase components. There was a high correlation between these events and a progressive disruption of the physiological voltage-versus-depth profile Conclusions: These observations suggest that epileptogenesis involves the disruption of physiological oscillatory patterns in the hippocampus while no severe clinical seizures are present. This disruption continues to progress, impairing network inhibition, promotes seizure severity and seizure susceptibility in temporal lobe epilepsy. HFOs may participate in propagated-seizure or kindling-like mechanisms while microseizures could reflect predictive cognitive impairment.