Abstracts

Rationale: Recording through arrays of multiple electrodes from neocortical slices from rats with chronic in vivo recurrent seizures can provide new insight into the basic mechanisms of chronic epilepsy. Yet, the trauma and the severing of connection related to dissecting slices can potentially disrupt the intrinsic hyperexcitability of a chronic epileptic cortex. We inquired whether brain slices from epileptic animals present features of hyperexcitability that may reflect the intrinsic epileptic hyperexcitability of the cerebral cortices from which the slices were prepared. 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 distribution of epileptic discharges was compared between slices of normal animals and those from control animals. Multiple cortical layers were involved by ictal and interictal activity in slices from both controls and tetanus toxin injected rats. In slices from normal animals discharges were segregated into several interconnected microscopic zones with a notched edge. In at least four slices these appeared independent initially and they gradually developed a synchrony throughout the recording. In slices from epileptic rats discharges exhibited higher voltages, with pronounced lateral spreading especially over superficial cortical layers so as to involve most of the recorded cortical area. Conclusions: Epileptiform activity in neocortical slices from a normal brain manifests as multiple independent but coalescing microzones of low voltage discharges. In neocortical slices from a chronic epileptic brain epileptic discharges exhibit higher voltages and pronounced lateral spread: epileptic hyper-excitability of a chronic epileptic brain is maintained in slices. In vitro recordings through multielectrode array slice preparation is providing novel insight on the basic mechanisms of both acute and chronic epilepsy.