Grant: Operating Grant

The causes of schizophrenia remain unclear, but there is strong evidence to suggest a genetic component to the disease. Even though the susceptibility genes that cause schizophrenia are inherited from birth, the symptoms of the disease are not fully apparent until after adolescence and into early adulthood. A prevailing hypothesis is that schizophrenia results when impairments in gene function cause improper neural communication and connection during childhood brain development. This would suggest that effective treatment of schizophrenia requires a rewiring of those brain circuits that mediate the symptoms of the disease. We are beginning to understand which brain regions and connections are responsible for the behavioural symptoms of schizophrenia, and can now explore questions about the ability of these circuits to be "rewired" either in adulthood or in earlier stages of development. Using a genetic mouse model of schizophrenia, we propose to study the ability of the brain to rewire and improve function by restoring proper neuronal communication at different stages of postnatal development and maturity. To see whether proper brain function is achieved, we will use behavioural paradigms that assess aspects of cognition, sociability, and sensory processing that are impaired in schizophrenia. We will also examine whether improvements in brain function are correlated with normalization of gene expression, neurochemistry, and brain structure. In performing these studies, we will gain an understanding of the brain's capacity to overcome developmental insults. Our studies will also help to determine whether early therapeutic intervention is beneficial for brain function in schizophrenic patients.