Zmieniona fizjologia i zaburzona aktywność specjalnych komórek zęba Ammona w mysim modelu epilepsji

The dentate gyrus is a major locus for structural and synaptic reorganization in temporal lobe epilepsy. While physiological changes during epileptogensis are well characterized in the principal dentate projection neuron, granule cells (GCs), epilepsy-related changes in semilunar granule cells (SGCs), a distinct subset of dentate projection neurons, remain unknown. Using a mouse pilocarpine model of epilepsy, we show that, unlike GCs, SGCs exhibit an increase in intrinsic excitability 1 week after status epilepticus (SE). GCs, not SGCs. have a lower threshold for action potential firing in mice 1-month post-SE. Both GCs and SGCs display increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) 1-week and 1-month after SE. Uniquely, SGCs received more frequent spontaneous inhibitory postsynaptic currents (sIPSCs) and exhibited smaller afferent-evoked IPSCs early after SE. Additionally, evoked EPSC amplitude in SGCs was reduced 1-month post-SE. Behaviorally, mice 1-month post-SE showed impairments in their ability to use spatial search strategies in a Barnes maze paradigm. Post-SE TRAP2::tdT mice showed reduced activity dependent neuronal ensemble labeling, with fewer tdT-labeled neurons in both task-naïve and trained conditions and reduced c-Fos co-expression following task re-acquisition compared to controls. Notably, the proportion of SGCs within labeled ensembles was reduced in task-naïve epileptic mice but not in trained animals. Collectively, our findings identify selective changes in SGC intrinsic excitability during epileptogenesis that could contribute to enhanced network excitability. The cell-specific alterations in SGC circuit connectivity during epileptogenesis, alongside the apparent reduction in neuronal recruitment to behavioral ensembles likely contribute to spatial navigation deficits observed in epilepsy.