High-frequency oscillations (HFOs), termed ripples and fast ripples , are recorded in the EEG of epileptic patients and in animal epilepsy models; HFOs are thought to reect pathological activity and seizure onset zones. Here, we analyzed the temporal and spatial evolution of interictal spikes with and without HFOs in the rat pilocarpine model of temporal lobe epilepsy. Depth electrode recordings from dentate gyrus (DG), CA3 region, subiculum and entorhinal cortex (EC), were obtained from rats between the 4th and 15th day after a status epilepticus (SE) induced by i.p. injection of pilocarpine. The first seizure occurred 6.1±2.5 days after SE (n=7 rats). Five of 7 animals exhibited interictal spikes that co-occurred with fast ripples accounting for 4.9±4.6% of all analyzed interictal spikes (n=12,886) while all rats showed interictal spikes co-occurring with ripples, accounting for 14.3±3.4% of all events. Increased rates of interictal spikes without HFOs in the EC predicted upcoming seizures on the following day, while rates of interictal spikes with fast ripples in CA3 reflected periods of high seizure occurrence. Finally, interictal spikes co-occurring with ripples did not show any specific relation to seizure occurrence. Our findings identify different temporal and spatial developmental patterns for the rates of interictal spikes with or without HFOs in relation with seizure occurrence. These distinct categories of interictal spikes point at dynamic processes that should bring neuronal networks close to seizure generation.

We analyzed with EEG-video monitoring the epileptic activity recorded during the latent and chronic periods in rats undergoing 30 or 120 min pilocarpine-induced convulsive status epilepticus (SE). Interictal discharges frequency in the entorhinal cortex (EC) of animals exposed to 120 min SE was significantly higher in the chronic than in the latent period. Following seizure appearance, interictal spikes diminished in duration in the CA3 of the 120 min SE group, and occurred at higher rates in the amygdala in all animals. Rats exposed to 120 min SE generated shorter seizures but presented twice as many non-convulsive seizures per day as the 30 min group. Finally, seizures most frequently initiated in CA3 in the 120 min SE group but had similar onset in CA3 and EC in the 30 min group. These findings indicate that convulsive SE duration influences the development of interictal and ictal activity, and that interictal discharges undergo structure-specific changes after seizure appearance.

The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg/kg i.p. for 4-24 weeks. We found that this pesticide reduced the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra; after the 4-week treatment the reduction (17%, nonsignificant) was confined to the rostrocentral region of this structure but, after 24 weeks, had spread along its whole length and was approximately 37%. Moreover, it induced a biphasic effect on dopaminergic transmission. First, levels of dopamine, its metabolites and turnover were elevated (4-8 weeks) in the caudate-putamen, then all these parameters returned to control values (12 weeks) and dropped by 25-30% after 24 weeks. The binding of [3H]GBR 12,935 to dopamine transporter in the caudate-putamen was decreased after 4-8 weeks, then returned to control values after 12 weeks but was again decreased after 24 weeks. Twenty-four-week paraquat administration also decreased the level of tyrosine hydroxylase (Western blot) in the caudate-putamen. In addition, paraquat activated serotonin and noradrenaline transmission during the first 12 weeks of treatment but no decreases in levels of these neurotransmitters were observed after 24 weeks. The above results seem to suggest that long-term paraquat administration produces a slowly progressing degeneration of nigrostriatal neurons, leading to delayed deficits in dopaminergic transmission, which may resemble early, presymptomatic, stages of Parkinson's disease.