Excitation/Inhibition Balance & Cognition in Schizophrenia: Building a Multi-Scale Understanding

The symptoms of schizophrenia which cause the most disability are problems thinking clearly, called 'cognitive symptoms'. Cognitive symptoms may stem from an imbalance in the way two types of brain cell interact, causing interference in how brain areas communicate with each other. Investigating these ideas is difficult as we do not have a good way to measure this imbalance in humans. I will develop a method for measuring this and validate this method by using it on genetically engineered mice (where we know for certain that the imbalance exists). I will study whether differences we see in mice are similar to what we see in patients. Finally, I will investigate how a treatment that may help cognitive symptoms (called memantine), works by investigating its effect on this imbalance. The results will help us understand the biological basis of cognitive symptoms, and how we may be able to treat them.