Grant: Project Grant

According to the Canadian Mental Health Association, 20% of Canadians will experience mental illness at some points during their lives. Schizophrenia is one mental illness that is particularly costly given its typical onset in early adulthood and persistence throughout life. Research supports the hypothesis that changes in brain circuits including those in areas of the cerebral cortex are involved in schizophrenia. However, how activity within and among these brain areas is altered is not well understood. Recent evidence suggests that reduced expression of perineuronal nets, structures in the tissue around cells that ensheath certain kinds of neurons, may contribute to brain dysfunction. The present proposal explores this connection using rodent models. Our series of experiments will assess the expression of perineuronal nets over the course of development in a well characterized rat model of maternal immune activation. Maternal immune activation (i.e. serious illness during pregnancy) is a risk factor for the development of schizophrenia in children, and this model results in behaviour in rat offspring consistent with schizophrenia. We have collected exciting preliminary data suggesting that perineuronal nets are reduced in the prefrontal cortex of offspring exposed to maternal immune activation while in utero. These changes are restricted to adulthood when the expression of perineuronal nets normally peaks and the symptoms of schizophrenia are expressed. In the second phase of the project, we will assess the effects of degrading perineuronal nets in prefrontal cortex using behavioural, electrophysiological, and imaging techniques. The long-term implications of this study may contribute to both new therapeutic strategies combatting the symptoms of schizophrenia, as well as interventions that prevent the loss of perineuronal nets following adverse events during development.