Functional anatomy of limbic seizures: focal discharges from medial entorhinal cortex in rat

Abstract

Focal seizure discharges were induced in the ventral aspect of the medial entorhinal cortex of awake, freely moving rats, either with cannula injections of penicillin or picrotoxin (0.02 microliters every 10-15 min) or by repetitive tetanic electrical stimulation. [14C]Deoxyglucose autoradiography (DG) was performed when animals were in a 'steady-state' with respect to electrographic discharges and/or behavioral changes. During simple interictal spikes behavior remained normal and DG labeling was increased only in the entorhinal focus and stratum moleculare of the ventral dentate gyrus. With complex spikes and short seizures animals exhibited staring, decreased responsiveness, and occasional wet dog shakes. DG labeling was increased in all layers of the dentate gyrus, Ammon's horn (ipsilateral greater than contralateral) and, to a lesser degree, in ipsilateral amygdala, and the accumbens-ventral pallidum area. During strong seizures, rearing and forelimb clonus occurred and metabolism was strongly activated bilaterally in the hippocampal formation, amygdala, accumbens, substantia nigra, and the anterior and periventricular thalamic nuclei. These studies indicate that the dentate gyrus initially restricts the entry of seizures from entorhinal cortex into the rest of hippocampus. As this is overcome there is rapid bilateral spread through the hippocampal formation with passive interruption of normal behavior. With prolonged seizure discharges there is further capture of amygdala and subcortical extrapyramidal and thalamic nuclei associated with behavioral convulsions.