Detection of increased local excitatory circuits in the hippocampus during epileptogenesis using focal flash photolysis of caged glutamate.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Biomedical Sciences Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523, USA.
Li-Rong
LR
Shao
F Edward
FE
Dudek
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology*; D007608:Kainic Acid; D008297:Male; D008959:Models, Neurological; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010782:Photolysis; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
D018698:Glutamic Acid; D007608:Kainic Acid