Abnormal cortical development is increasingly recognized as a cause of developmental disabilities and epilepsy but the physiopathological mechanisms remain still obscure. Here we investigated this issue in an animal model of band heterotopia induced by in utero knockdown of doublecortin.

Video ECoG recordings of DCX knockdown animals revealed the presence of numerous spontaneous paroxysmal events. They were characterised by increased of alpha-beta activities associated with either no major behavioural changes or behavioural immobility and minimal facial myoclonic jerks or stereotypes.

We have observed a strong reduction of the frequency of spontaneous EPSCs and IPSCs in ectopic neurons as compared with normal L2/3. In addition, the activity of untransfected overlying L2/3 neurons was modified though they migrated to the appropriate layer: they displayed a strong increase in the frequency of EPSCs as compared with neurons in normal L2/3. Electrode microarray investigations on cortical slices revealed an increased susceptibility to epileptiform agents on DCX knockdown sections; Current sink and source patterns analysis revealed important changes of network operation on the cortex overlaying the heterotopias that strongly support the notion that it becomes epileptogenic. We conclude that the genesis of heterotopia combined with the subsequent alteration of overlaying neocortex result in increased brain excitability and seizures.