The long-term goal of the proposed research is to obtain information about basic mechanisms in the production of seizures. Slices of rat neocortex maintained in vitro will be used as a model system for the study of a novel type of epileptiform activity we have observed in immature animals. Quantitative neurophysiological techniques will be used to examine the contributions of synaptic potentials, changes in the extracellular ionic environment, and alterations in the characteristics of single calcium channels to the generation of epileptiform discharges. Using intracellular recording techniques, the alterations in membrane potential and input resistance associated with paroxysmal depolarizing shifts and long-lasting depolarizations (LLDs) will be determined. We will also ascertain whether a synaptic input with a demonstrable reversal potential initiates LLDs. Ion-selective microelectrodes will be used to examine the mechanisms underlying LLDs and to determine whether LLDs are an ictal event or a type of spreading depression. Ionic changes will be correlated wit simultaneously recorded changes in membrane potential. Finally, patch-clamp recordings of single ionic channels will be made to investigate the hypothesis that the transient changes in extracellular calcium concentration seen during epileptiform discharges result in alterations of channel properties. Clinical seizure disorders are a significant medical problem. The proposed research is directed toward a better understanding of the mechanisms underlying paroxysmal discharges in the brain. Research such as this will contribute to a better understanding of modes of communication among neurons and will eventually lead to advances in the management of clinical seizure disorders.
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