The long-term objective of this research is to understand the neural mechanisms of epilepsy. This proposal focuses on the physiology and possible behavioral dysfunctions of kindled spontaneous interictal spikes (SISs) in the hippocampus. It is hypothesized that hippocampal SISs in the CA1 region results from spontaneous neuronal bursting in CA3, through synapses that undergo long-term potentiation. Spaced electrical stimulations through chronically indwelling electrodes in the hippocampus of the rat (kindling) will serve as a model of epilepsy. The CA3 and CA1 evoked responses following stimulation of the stratum oriens and stratum radiatum, and the hippocampal SIS rate in the animals will be studied after daily tetanizations until seizures are evoked. Similar time courses of change of evoked responses and SIS rate may suggest a common underlying mechanism, possibly long-term potentiation. In the seizing animals, the relations between seizures and SISs, and the behavioral (sleep) relation of seizures and SISs will be studied by 24-hour computer-aided recordings. The intracellular correlates of kindled interictal spikes will be studied in urethane-anaesthetized animals to reveal the depolarization and hyperpolarization that may accompany the different types of SISs. Hippocampal slices from kindled, especially spontaneously seizing rats, will be compared to normal rats in their ability to sustain SISs, in CA3/CA1 evoked population excitability, and in the intrinsic membrane properties of CA3 and CA1 neurons. In addition, the behavioral dysfunctions of the hippocampus in relation to the SISs will be studied in an open 8- arm maze. By manipulating the SIS rate by cessation of tetanizations, the relation between maze-performance and the frequency of SIS may be revealed. A better understanding of the interictal spikes may result in a more efficient diagnosis and perhaps in the treatment of epilepsy.
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