[P1.31]: Abducens motor neurons share origins with oligodendrocytes and potentially provide a positional cue for facial motor neuron migration

Emergence of the hilar ectopic granule cells is a well-known pathological aberration found in the dentate gyrus of temporal lobe epilepsy patients. However, the cellular mechanisms underlying the phenomena remain to be elucidated. In this study, we asked if early-life febrile seizures affect the normal migration of the granule cells in the postnatal hippocampus because the development of the granule cell layer is almost completed in the postnatal periods when most of the patients experience febrile seizures. To investigate themechanisms that regulate the granule cell migration, we developed a novel slice coculture system. We prepared the hilar micro-slices from early-postnatal transgenic rats expressing green fluorescent protein and inserted them to the hippocampal slices from wild-type littermates. Using confocal microscopy, we succeeded in the real-time imaging of the migrating granule cells. The immature granule cells had long leading processes and performed the radial migration to the granule cell layer. We found that the granule cells migrate reversely in the hilus when the hilar slices were derived from rats that underwent experimental febrile seizures. The reverse migration was blocked by a bath application of the GABAA receptor antagonist bicuculline. We also found that muscimol, a GABAA receptor agonist, slows down or reverses the migration of the granule cells which originate from the wild-type hilar slices. These results suggest that GABAA receptor activation interrupts the normal migration of the immature granule cells in the postnatal hippocampus undergoing febrile seizures. Considering that the development of the dentate gyrus is mostly completed postnatally, the slowly or reverselymigrating granule cells during the periods likely give rise to the hilar ectopic granule cells later in life.