Activation of the glutamatergic system of the medial septal area accelerates epileptogenesis

The effects of injection of L-glutamate into the medial septal area on epileptogenesis associated with stimulation of the perforant pathway were studied in conscious guinea pigs. EEG field potentials were recorded in the hippocampus and medial septal area in the initial state and on formation of epileptic foci in animals given physiological saline (controls) or L-glutamate (glutamate group) into the medial septal area. Administration of glutamate enhanced the theta rhythm in both structures. During kindling in animals given glutamate, there was significantly earlier onset of the convulsive state and secondary epileptiform discharges than in controls. As the epileptic focus formed, sharp weakening of theta oscillations was seen in all animals, though onset was much earlier in the glutamate group. The correlation between the hippocampal and septal EEG decreased sharply in animals given glutamate, while changes in controls were minor. These results are of value in deciphering the mechanisms of temporal epilepsy.