RAPID AND TRANSIENT INCREASES IN CELLULAR IMMEDIATE-EARLY GENE AND NEUROPEPTIDE MESSENGER-RNAS IN CORTICAL AND LIMBIC AREAS AFTER AMYGDALOID KINDLING SEIZURES IN THE RAT

Changes in transcription factor and neuropeptide gene expression are l ikely to be involved in the cascade of genetic and molecular events le ading to permanent changes in neuronal activity associated with kindli ng and epilepsy. Both acute-transient and delayed-sustained changes in transcription factor or immediate early gene (IEG) activity have prev iously been reported in response to different stimuli. In the present study in situ hybridization was used to investigate the possible time course (30 min-8 week) of IEG and neuropeptide mRNA induction in foreb rain in a kindling model of epilepsy. Kindling was produced by daily u nilateral stimulation of the amygdala. IEG mRNAs were detected using [ S-35]-labelled oligonucleotide probes specific for c-fos, c-jun, NGFI- A (PC1) and PC3 transcripts. possible changes in the level of mRNAs en coding the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY) w ere also studied. Stimulation-induced seizures produced dramatic bilat eral increases in all IEG mRNAs in the dentate gyrus after 30 min to 1 h. Ipsilateral or bilateral increases in c-fos and PC3 mRNA were obse rved in the piriform cortex of individual animals at 30 min post-stimu lation. While the distribution and apparent basal expression of the di fferent IEGs varied (NGFI-A and c-jun > c-fos and PC3), the degree of induction in the dentate gyrus was similar for all IEGs studied (i.e. 200-300%). No long-term changes in IEG mRNA expression were detected b eyond 2 h and up to 8 week after the last seizure. Increased levels of preproSOM and preproNPY mRNAs were consistently observed in hilar int erneurons, but not in pyramidal or granule cells of the hippocampus, a fter 1-2 h. These increases were not maintained at later times. The sh ort-term effects on IEG and neuropeptide mRNAs observed suggest that t hese changes are a consequence of seizure activity associated with the development of kindling. In contrast, no evidence was found of any su bstantial, long-lasting effects on these parameters associated with th e established kindled state.