Abstracts

Rationale: Seizure activity is associated with changes in both hippocampal dentate granule cell morphology and integration. These changes are evident in different models of epilepsy including status epilepticus models, genetic models and traumatic brain injury models. All of these models are associated with substantial neuron loss and the development of spontaneous recurrent seizures. By contrast, it is possible in the kindling model to administer a limited number of stimulations sufficient to produce a lifelong enhanced sensitivity to stimulus evoked seizures without associated spontaneous seizures. Here we asked whether stimulations sufficient to induce enhanced sensitivity to evoked seizures, but not frank epilepsy, will induce morphological changes similar to those observed in other models of epilepsy Methods: Thy-1 GFP expressing transgenic mice were used to analyze granule cell morphology in kindled and control animals. Morphological parameters examined included soma area, apical dendrite number, basal dendrite number, axon varicosity density, the relative position of the cell within the granule cell layer, spine density and the thickness of the granule cell layer. Animals were examined either one day or one month after experiencing five kindling-evoked seizures. Results: We observed an increase in the thickness of the granule cell body layer and a decrease in the number of spines in the inner and outer molecular layers one day after kindling. No differences were observed between control and kindled animals among any of the other parameters examined. However, by one month after kindling, granule cells from control and kindled animals were indistinguishable, indicating that the acute changes observed are transient. Conclusions: These findings demonstrate that kindling epileptogenesis does not produce the striking rearrangements of granule cell structure seen in other models of epilepsy, such as hilar projecting basal dendrites - at least for the cell populations examined. Whether the absence of robust restructuring in these animals accounts for the absence of spontaneous seizures remains to be determined.