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- Experimental Febrile Seizures Induce Ectopic Granule Cells in Vivo
- GABAA-R Signaling Regulates Granule Cell Migration and Localization
- Aberrant Migration of Granule Cells after Febrile Seizures: Findings from a Novel Coculture System
- NKCC1 Inhibition Prevents Granule Cell Ectopia and Development of Epilepsy
Epilepsy is a nervous system disorder characterized by recurrent seizures. Among several types of epilepsy, which accounts for a significant portion of the disease worldwide, temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy in adulthood. It has been suggested that complex febrile seizures in early life are associated with the development of TLE later in life; however, cellular and molecular links between febrile seizures and TLE remain unclear because of the lack of an appropriate in vitro system. Using rat hippocampal slice cultures, in which many features of native organotypic organization are retained, we found that the dentate granule cells exhibit aberrant migration in the dentate hilus via enhanced excitatory GABAA receptor (GABAA-R) signaling, which results in granule cell ectopia that persists into adulthood. We further found that the granule cell ectopia is associated with spontaneous limbic seizures in adulthood. Importantly, both of these phenomena were prevented by inhibiting Na+K+2Cl− co-transporter (NKCC1) which mediates the excitatory action of GABA.