AMYGDALA KINDLING POTENTIATES SEIZURE-STIMULATED IMMEDIATE-EARLY GENE-EXPRESSION IN RAT CEREBRAL-CORTEX

Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute electroconvulsive seizure (ECS). Although amygdala kindling did not significantly influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in the cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was dependent on the time course of kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased in stage 2 kindled animals. ECS-stimulated levels of c-jun and NGF1-A mRNA were also significantly increased in cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was long-lasting because an acute ECS stimulus significantly elevated levels of c-fos and c-jun mRNA in the cerebral cortex of animals that were kindled 5 months previously. In contrast to these effects in cerebral cortex, kindling did not influence ECS-stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical studies revealed lamina-specific changes in the cerebral cortex. In sham-treated controls, acute ECS resulted in an increase in the number of Fos-like immunoreactive (Fos-li) neurons in layers II + III and V of prefrontal cortex, which approached significance; ECS did not influence the number of Fos-li neurons in layer VI. However, in kindled animals acute ECS significantly increased the number of Fos-li neurons in layers II + III and V of prefrontal cortex. These results suggest that kindling increases the responsiveness of cerebral cortical neurons to certain stimuli and that regulation of IEG expression could be involved in the molecular adaptations that underlie kindling.