Funding outcome

The hippocampus, a central hub for learning and memory and the 'gate' of seizure threshold, begins forming during embryonic development. Throughout development, many neurons undergo mass cell death. Though beneficial, it can have severe consequences if it is not correctly regulated. Cajal-Retzius (CR) cells are a set of neurons that play a crucial role in brain development. The majority of CR cells are fated to die by apoptosis, but in the hippocampus, the mechanism is unknown. Incomplete clearance of hippocampal CR cells has been associated with difficult-to-treat epilepsy in children. My preliminary data indicates that knockout of capicua (CIC), a gene important for brain development, prevents CR cell death in the mouse hippocampus. Interestingly, mutations of CIC in humans lead to a rare neurodevelopmental disorder characterized by neurological deficits and seizures in children. Given the common link of both CIC mutations and improper CR cell death with epilepsy, I will use CIC knockout mice as a tool to study the regulation of CR cell death and the role of CR cells in epilepsy. First, I will investigate the mechanism of hippocampal CR cell death by comparing the expression of cell death-related genes in control and knockout mice. Secondly, I will investigate the role of CR cells in epilepsy by manipulating neural activity of these cells in prepubescent mice and assessing seizure development. This project will provide an insight into the role hippocampal CR cells play in epilepsy. Understanding the CR cell death mechanism opens the possibility of exploiting it to treat diseases due to CIC mutations and epileptic disorders on a broader scale.