Funding outcome

Epilepsy affects about 1 in 200 children in Canada. Treatment of epilepsy presents a complex challenge because it is caused by vastly different mechanisms that perturb wiring of the brain. As a result, 30%-40% of epilepsy patients do not respond to drug treatments. Children with uncontrollable epilepsy are not only at a higher risk of mortality but also more likely to have learning disabilities, depression, and anxiety, leading to reduction in quality of life. Further insight into the cause of treatment-resistant epilepsy is needed to develop effective therapies for children suffering from this devastating neurological condition. Cajal-Retzius cells are a type of nerve cells that are mostly found in the brain during embryonic development but are largely eliminated in the postnatal brain. Intriguingly, in brain tissues from patients undergoing epilepsy surgery, high densities of Cajal-Retzius cells have been reported. This suggests a role of Cajal-Retzius cells in difficult-to-treat epilepsy. But how Cajal-Retzius cells contribute to epilepsy development is unknown. Addressing this question has proven challenging, partly due to the lack of animal models that mimic the human pathology of abnormal Cajal-Retzius cell persistence. Here, we have developed a unique mouse model with abnormal persistence of Cajal-Retzius cells in the postnatal brain. We design a set of experiments to investigate how Cajal-Retzius cell death is regulated. We will also determine whether abnormal Cajal-Retzius cell persistence and their aberrant activity alter early postnatal brain development and contribute to increased seizure susceptibility.