Abstracts

The chronic stage in pilocarpine-treated rats (with spontaneous seizures), a model of Temporal lobe Epilepsy, is characterized by a profound reorganization of the CA1 region of the hippocampus. Specific subpopulations of interneuron die resulting into a decrease of dendritic inhibition on pyramidal cells, whereas the remaining interneurons become hyperactive resulting in an increase of inhibition on the soma of pyramidal cells. To date, it is not possible to determine whether these modifications are the cause or the consequence of seizures. In order to start to address this issue we have studied the time course of these modifications. We have focused on the latent period, i.e. the time between the pilocarpine-induced status epilepticus and the first spontaneous seizure. We have analyzed the inhibitory and excitatory inputs received by interneurons and pyramidal cells 7-9 days after pilocarpine injection and compared them to sham-treated animals and pilocarpine-treated animals with recurrent seizures.
In vivo recordings were performed in freely moving adult rats before and after pilocarpine injection. Animals were used for experiments 7-9 days after the injection (latent period) or after 45 days (chronic stage). Slices were harvested and interneurons and pyramidal cells were recorded in whole cell mode under visual control. All neurons were morphologically identified post hoc. The frequency and the kinetics of GABAergic and glutamatergic spontaneous and miniature curents were analyzed.
, the frequency of spontaneous excitatory post synaptic current (sEPSCs) is already increased during the latent period (4.14 Hz in pilo +7 days ; 3.43 Hz in chronic and 0.66 Hz in control rats). The frequency of spontaneous inhibitory currents (sIPSCs) is smaller than in chronic and control stage (9.13Hz in pilo + 7days vs 24.3 Hz in chronic and 19.8 Hz in control). Miniature GABAergic activity is already lost (1.6 Hz in pilo +7 days vs 6.3 Hz in chronic and 14.8 Hz in control)
, the frequency of sIPSCs and mIPSCs is also smaller than in control and chronic animals (7 Hz [amp] 2 Hz respectively in pilo + 7days vs 12.2 Hz [amp] 7.8 Hz in chronic and 12.5 Hz [amp] 7 Hz in control).The frequency of sEPSCs and mEPSCs is increased in comparison to control but remains smaller than in chronic animals (4.7Hz [amp] 1.5 Hz respectively in pilo + 7 days; 11.2 Hz [amp] 2.3 Hz in chronic and 1.6 Hz [amp] 1Hz in control). The kinetics of excitatory and inhibitory inputs on the interneurons is altered during the latent period only, being faster or slower according to the class of interneuron. There is no modification during the chronic stage as compared to control.
The balance between the excitatory and inhibitory input is already affected during the latent period but is not sufficient to generate seizures. However, the transient modification of the kinetics of synaptic currents may be important for epileptogenesis.
[Supported by: INSERM]