Expression of the proto-oncogene c-fos following electrical kindling in the rat

Kindling is a permanent form of brain change that results from repeated elicitation of epileptiform neural activity. c-fos has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes that occur during kindling. This study investigated the enhancement of c-fos levels following kindled seizures and the role of c-fos in the plastic changes underlying kindling. Male hooded rats were electrically kindled in the amygdala and the resulting c-fos and c-Ha-ras gene expression was quantified using Northern blot hybridization analysis. The results indicated that c-fos was constitutively expressed in forebrain and cerebellum, and that basal levels of c-fos were equivalent in naive and in fully kindled rats that have been seizure-free for 3 weeks. Following an amygdala-piriform kindled seizure there was a massive and transient increase in c-fos levels throughout forebrain and cerebellum. Although enhanced c-fos levels were correlated with afterdischarge (AD) duration in the kindled site, enhanced c-fos levels were also observed in the amygdala-piriform contralateral to the kindled site, and the enhancement did not depend on the occurrence of AD in the contralateral amygdala-piriform. Furthermore, electrical stimulations not resulting in AD as well as other forms of control stimulation also increased c-fos levels. We conclude that c-fos was expressed simply as a consequence of neural activity and not exclusively due to the specific neural activity or underlying plastic change required for kindling. This does not preclude a role for c-fos in the long-term response to external stimuli, but it does suggest that c-fos is not the crucial 'master switch' in turning on a molecular program that might underlie kindling.