An in vitro seizure model from human hippocampal slices using multi-electrode arrays

Temporal lobe epilepsy is a neurological condition marked by seizures, typically accompanied by large amplitude synchronous electrophysiological discharges, affecting a variety of mental and physical functions. The neurobiological mechanisms responsible for the onset and termination of seizures are still unclear. While pharmacological therapies can suppress the symptoms of seizures, typically 30% of patients do not respond well to drug control. Unilateral temporal lobectomy, a procedure in which a substantial part of the hippocampal formation and surrounding tissue is removed, is a common surgical treatment for medically refractory epilepsy. In this study, we have developed an in vitro model of epilepsy using human hippocampal slices resected from patients suffering from intractable mesial temporal lobe epilepsy. We show that using a planar multi-electrode array system, spatio-temporal inter-ictal like activity can be consistently recorded in high-potassium (8 mM), low-magnesium (0.25 mM) artificial cerebral spinal fluid with 4-aminopyridine (100 μM) added. The induced epileptiform discharges can be recorded in different subregions of the hippocampus, including dentate, CA1 and subiculum. This new paradigm will allow the study of seizure generation in different subregions of hippocampus simultaneously, as well as propagation of seizure activity throughout the intrinsic circuitry of hippocampus. This experimental model also should provide insights into seizure control and prevention, while providing a platform to develop novel, anti-seizure therapeutics.