Misplaced and misconnected: circuit-level defects in malformations of cortical development

During histogenesis of the cerebral cortex, a proper laminar placement of defined numbers of specific cellular types is necessary to ensure proper functional connectivity patterns. There is a wide range of cortical malformations causing epilepsy and intellectual disability in humans, characterized with various degrees of neuronal misplacement, aberrant circuit organization or abnormal folding patterns. Although progress in human neurogenetics and brain imaging techniques have considerably advanced the identification of their causative genes, the pathophysiological mechanisms associated with defective cerebral cortex development remain poorly understood. In my presentation, I will outline some of our recent works in rodent models illustrating how misplaced neurons forming grey matter heterotopia, a cortical malformation subtype, interfere with the proper development of cortical circuits, and induce both local and distant circuitry changes associated with the subsequent emergence of epilepsy.