Abstracts

Rationale: Basic neurophysiological mechanisms of epilepsy have been traditionally explored in experimental models by inducing seizures acutely through pro-convulsant agents. People with epilepsy suffer from recurrent unprovoked seizures and epilepsy is a chronic condition. Yet only few studies have investigated the changes in network properties of the neocortex in chronic epilepsy. In vitro studies from neocortical slices from rats with and without chronic in vivo recurrent seizures can disclose how epileptic hypersynchrony and hyperexcitability are altered in slices and, may provide new insights into mechanisms of epileptogenesis. Sampling of extracellular activity simultaneously over multiple spatial locations can reveal the spatial and temporal organization of epileptic activities. Methods: Tetanus toxin was injected in the somatosensory cortex of adult rats and subsequent in vivo EEG recordings were performed to monitor the development of epileptic activity. Coronal slices of somatosensory cortex were prepared from brains of rats exhibiting frequent in vivo EEG seizures. In vitro epileptic activity was induced with zero magnesium and 4-Aminopyridine (4-AP). Recordings were performed through Multi-Electrode arrays (MEAs). Slices from age matched rats without tetanus toxin injections were used as controls. Results: Brain slices were prepared two weeks after the tetanus toxin injection after the development of interictal spiking and seizures recorded with long term video EEG monitoring in vivo. The spatial and temporal organizationof interictal and ictal epileptic discharges were compared to slices from control animals. Repetitive seizure-like activities were typically ~two fold larger in amplitude than those from controls and involved different cortical layers. In the tetanus toxin injected rats, interictal discharges from the slices exhibited only slightly larger amplitudes and their frequency of occurrence was similar to that of controls. Multiple cortical layers were involved by ictal and interictal activity in slices from both controls and tetanus toxin injected rats, however, the seizures tended to involve a predominantly more columnar architecture.Conclusions: The presence of larger ictal discharges in neocortical slices from rats with chronic epilepsy compared to control animals suggests a significant alteration of neocortical networks leading to chronic hypersynchrony that involves deep and superficial cortical layers. Basic mechanisms of chronic epilepsy can be investigated using an vitro multielectrode array slice preparation.