To investigate the cell type-specific role of hippocampus in a "two-hit" rat model of cortical dysplasia

Cortical dysplasia is one of the most common causes of drug-refractory epilepsy and its treatment remains a clinical challenge. Temporal lobe, apart from the cortex, is frequently identified as the epileptogenic zone in cortical dysplasia patients. As a temporal lobe structure vulnerable to epileptogenesis, the cell type-specific role of hippocampus in cortical dysplasia remains elusive.

In the "two-hit" rat model of cortical dysplasia, structural and functional alteration of hippocampus was studied with immunostaining and electroencephalogram analysis respectively. Density of cells that expressed neuronal nuclei (NeuN), parvalbumin (PV) and somatostatin (SST) in the hippocampus was estimated. Next, their functional roles in seizures were evaluated by optogenetic manipulation. The relationship between cell types were further examined from patch-clamp recordings on the brain slices from cortical dysplasia rats. 

The paradoxically excitatory SST-positive neurons in the dentate gyrus of hippocampus play a major role in cortical dysplasia-related seizures. Targeting GABAergic neurons as a whole, therefore, may not be a viable therapeutic strategy for cortical dysplasia patients.