The goal is to contribute to the understanding of neuronal interactions that underlie seizure activity in the cerebral cortex. Piriform cortex will be used for the proposed experiments because it is highly susceptible to epileptogenesis, may play an important role in temporal lobe epilepsy, and has structural, physiological, and pharmacological features that qualify it as a model system for study of cerebral cortex. The proposed experiments will focus on long-lasting """"""""induction"""""""" processes that are believed to be involved in the development and progression of some forms of epilepsy, and on neuronal mechanisms that underlie spread of seizure activity from epileptic foci. Studies of long-lasting induction processes will be carried out by physiological analysis of the chances that underlie the development of epileptiform EPSPs in slices of piriform cortex subjected to bursting activity, and in slices from rats in which epilepsy has been """"""""kindled"""""""" by repeated shock stimulation. Previous studies have localized the neurons in which the induced changes take place; in the proposed studies hypotheses concerning the identity of these changes will be tested using intracellular recording techniques. Studies of the mechanism of spread of epileptiform activity will be carried out on an anaesthetized rat preparation in which interictal- and ictal-like epileptiform activity spreads throughout the piriform cortex and adjacent cortical areas when a pharmacologically disinhibited focus is repetitively activated by 1 or 2 Hz shock stimulation. The hypothesis will be tested that repetitive bursting activity conducted from the focus by association axons induces a transient reduction in inhibitory processes in the surrounding cortex, thereby initiating a slow regenerative spread of epileptiform activity. Changes will be analyzed in each of the 4 inhibitory processes that have been identified. These studies will employ intracellular recording and current source-density analysis techniques in an anaesthetized rat preparation. Current source-density analysis gives a graphic picture of the sequence of neuronal events over depth and time via mathematical analysis of extracellularly recorded field potentials. To assist in interpretation of the physiological results, both local axon collateral systems and projection pathways that are believed to be involved in the induction and spread of seizure activity will be studied morphologically. Techniques to be used include intracellular injection of biocytin in slices maintained in vitro, and extracellular injection of Phaseolus vulgaris leucoagglutinin (PHA-L) in intact animals.
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