Epilepsy is a neurological disorder affecting many people. However, for ethical and technical reasons, research aimed at understanding the basic mechanisms underlying the epileptiform disorder has been carried out primarily with various animal models of epilepsy. These studies have provided considerable information about how abnormal discharge might arise, but the relevance of these data to epilepsy, as it occurs in human patients, is often unclear. The in vitro slice preparation offers us a method whereby electrophysiological, morphological, and pharmacological access to human epileptic tissue is facilitated. We propose to continue our studies of human epileptic tissue using this in vitro technique. Slices (600 um thick) of human temporal cortex will be made from tissue removed during neurosurgical procedures for intractable epilepsy. Cells from both lateral and mesial temporal cortex will be studied using intracellular techniques. We will characterize the passive and synaptic properties of each cell (i.e., input resistance, resting potential, action potential parameters, cellular response to stimulation) and attempt to correlate these measures with cellular morphology by injecting cells with intracellular labels. Special attention will be focused on cellular bursting activity and presence of inhibitory postsynaptic potentials (IPSPs). Recent slice studies of human tissue have yielded evidence of spontaneous rhythmic synchronous events (SRSEs) in some tissue samples; the basis for such activity will be investigated using simultaneous intracellular recordings (to study synchrony) and various ion blockers (to evaluate underlying synaptic mechanisms). The tissue will also be challenged with excitatory agents (high potassium concentration, GABA blockers) to see if epileptogenic properties can be uncovered, accentuated, or attenuated. Finally, single cell electrophysiology and morphology will be related to general tissue pathology. These studies will provide descriptive and mechanistic information about abnormal cellular properties in human epileptic tissue, information that will help us to better define the epileptic focus. In addition, such cellular studies will act as a bridge by which we can interpret and relate data from experimental models of epilepsy to cellular activity in human epileptic brain.
| Schwartzkroin, P A; Haglund, M M (1986) Spontaneous rhythmic synchronous activity in epileptic human and normal monkey temporal lobe. Epilepsia 27:523-33 |
