DEVELOPMENTAL AND SEIZURE-RELATED REGIONAL DIFFERENCES IN IMMEDIATE-EARLY GENE-EXPRESSION AND GABAERGIC ABNORMALITIES IN THE BRAIN OF EL MICE

To examine the hypothesized role of the immediate early gene (IEG) res ponse in synaptic plasticity and in epileptogenesis, we studied the sp atial specificity of the expression of IEG in EL mice, a well known mu tant model of epilepsy. Also to examine the 'GABA hypothesis' in epile psy, GABA concentration and GAD activity was determined in micro brain regions (10-300 ng) of EL mice related to the focus in the parietal c ortex and the hippocampus. We found that the IEG expression after seiz ures is not related to the seizure pattern, but to the seizure history , seizure threshold and development of EL[s]. Even in the interictal p eriod, EL mice with long seizure histories and very low seizure thresh olds demonstrate IEG expression continuously. This is probably strengt hened by repeated seizures. The IEG expression site is however located in the hippocampal CA1, which is the final terminal of various inputs from other areas of the limbic system. It is proposed that the contin uous expression of IEGs might play a different role from that of trans iently expressed IEGs. Developmentally, the site of IEG expression shi fted from one site to another in a very similar manner as in the IEG e xpression with propagation of paroxysmal discharges in each seizure, a nd the three-dimensional expression area was gradually expanded, sugge sting a change in the regional active site during epileptogenesis. The se lines of evidence suggest that during development as well as repeti tive seizures, frequent expressions of IEGs and syntheses of Fos and Z if proteins might facilitate synaptic conductivity involved in epilept ogenesis. The sites of abnormal GABA concentrations and GAD activities were almost the same in the parietal cortex, around Sidman atlas coro nal section No. 300 and in the hippocampal CA1 pyramidal cells as the spatio-temporal specific IEG expression sites. These findings strongly suggest that IEG expression and abnormal GABAergic function are invol ved in epileptogenesis in EL mice.