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1 Swammerdam Institute for Life Sciences
2 University of Amsterdam
* To whom correspondence should be addressed. E-mail: j.a.gorter{at}uva.nl.
A change in neuronal network excitability within the hippocampus is one of the hallmarks of temporal lobe epilepsy (TLE). In the dentate gyrus (DG), however, neuronal loss and mossy fiber sprouting are associated with enhanced inhibition rather than progressive hyperexcitability. The aim of this study was to investigate how alterations in excitability take place in association with spontaneous seizures expressed in the DG, before, during and after a seizure. For this purpose, we used freely moving rats that had developed spontaneous seizures after a kainate induced status epilepticus (SE). Continuous EEG was recorded in the DG during several days along with local field potentials (LFP) that were evoked every 15-30 seconds, by applying paired-pulse stimuli to the angular bundle. Input-output relations showed increased paired pulse depression in epileptic compared to control rats, suggesting a rather strong inhibition in the DG during the interictal state. A characteristic pattern of changes in intrinsic excitability was observed during the ictal period: an increase in the population spike (PS) amplitude, mostly during the early phase of a seizure and often followed by a decrease of the main evoked potential amplitude. The paired-pulse extracellular postsynaptic potential (fEPSP) ratio increased during the seizure and did slowly recover to pre-seizure levels after the seizure ended. Although, clear changes in excitability occurred during and after seizure activity, changes of LFP parameters were more subtle before seizure onset; a significant reduction of LFP and PS amplitudes was observed that started 1-2 minutes in advance in ~33% of the cases; in ~18% an increase of LFP/PS amplitude was observed; in the other cases no significant change was observed. Taken together, the present results provide evidence that in this experimental model, DG physiology is more likely to follow the already ongoing seizure activity rather than contributing to its generation.
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