Ute Häussler (Neurocenter, University Medical Center Freiburg)

Abstract:
Temporal lobe epilepsy (TLE) is characterized by altered structural plasticity in the dentate gyrus, including granule cell dispersion (GCD), cell loss, mossy fiber sprouting and altered neurogenesis in the subgranular zone (SGZ). It is, however, unresolved, how these changes contribute to the occurrence of epileptiform activity. To address this issue, we used the intrahippocampal kainate mouse model for TLE which recapitulates the main features of human TLE. We show that the initial status epilepticus and recurrent epileptiform activity are not strongest at the sites with the most prominent histological changes but in adjacent areas. Quantitative histological analysis revealed that interneurons are not lost but reduced at these sites with differential vulnerability of different interneuron types. In contrast, there is an upregulation of neurogenesis at these sites and young granule cells show intrinsic hyperexcitabiliy. These changes might comprise a network with disturbed excitation-inhibition balance that develops the capacity to generate epileptic seizures. Our precise quantitative analysis of interneurons and neurogenesis along the whole hippocampus paves a way for modelling studies on epileptogenicity of the altered hippocampal network.