Li-Rong Shao1, F Edward Dudek. 1. Department of Biomedical Sciences Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523, USA.
Abstract
PURPOSE: Local synaptic circuits, particularly recurrent excitation, are hypothesized to contribute to the generation and synchronization of epileptiform activity. The present study tested whether local excitatory circuits in the hippocampus are increased in an animal model of temporal lobe epilepsy, and thus may contribute to epileptic seizures. METHODS: Rats were given hourly injections of kainic acid to induce status epilepticus, which led to chronic epilepsy with spontaneous recurrent seizures. Whole-cell recording was performed in hippocampal slices, and focal flash photolysis of caged glutamate was used to detect local excitatory circuits. RESULTS: In the dentate gyrus of rats with kainate-induced epilepsy and mossy fiber sprouting, focal stimulations with caged glutamate at many different sites in the granule cell layer consistently evoked repetitive excitatory postsynaptic currents (EPSCs) in normal medium and prolonged bursts of action potentials in bicuculline; these responses were not observed in similarly treated slices from control rats. In CA1, focal flash photolysis of caged glutamate in stratum pyramidale revealed significantly more excitatory connections between CA1 pyramidal cells in rats with kainate-induced epilepsy than saline-treated control animals. CONCLUSION: Focal flash photolysis of caged glutamate revealed that new local excitatory circuits are formed in both the dentate gyrus and CA1 area of rats with kainate-induced epilepsy, which supports the hypothesis that the progressive formation of new local excitatory circuits occurs in many locations during epileptogenesis.
PURPOSE: Local synaptic circuits, particularly recurrent excitation, are hypothesized to contribute to the generation and synchronization of epileptiform activity. The present study tested whether local excitatory circuits in the hippocampus are increased in an animal model of temporal lobe epilepsy, and thus may contribute to epileptic seizures. METHODS:Rats were given hourly injections of kainic acid to induce status epilepticus, which led to chronic epilepsy with spontaneous recurrent seizures. Whole-cell recording was performed in hippocampal slices, and focal flash photolysis of caged glutamate was used to detect local excitatory circuits. RESULTS: In the dentate gyrus of rats with kainate-induced epilepsy and mossy fiber sprouting, focal stimulations with caged glutamate at many different sites in the granule cell layer consistently evoked repetitive excitatory postsynaptic currents (EPSCs) in normal medium and prolonged bursts of action potentials in bicuculline; these responses were not observed in similarly treated slices from control rats. In CA1, focal flash photolysis of caged glutamate in stratum pyramidale revealed significantly more excitatory connections between CA1 pyramidal cells in rats with kainate-induced epilepsy than saline-treated control animals. CONCLUSION: Focal flash photolysis of caged glutamate revealed that new local excitatory circuits are formed in both the dentate gyrus and CA1 area of rats with kainate-induced epilepsy, which supports the hypothesis that the progressive formation of new local excitatory circuits occurs in many locations during epileptogenesis.