Grant: Discovery Grants Program - Individual

Perinatal (i.e. around the time of birth) brain development is a complex and highly dynamic period in all mammals, including rats and humans. The brain growth spurt in particular, which occurs in late 3rd trimester in humans but in the first 3 postnatal weeks in rats, is a time of massive changes in brain chemistry and in the connections formed between neurons, that will ultimately determine brain function. The complexity of the brain growth spurt also makes it a window of vulnerability for the developing organism, in which seemingly minor trauma or chemical toxicity can result in developmental abnormalities that later manifest in neurological disease. Many of society's most important neurological disorders are often neurodevelopmental in origin, including epilepsy, cerebral palsy, autism, and schizophrenia. Schizophrenia is a psychiatric diagnosis that describes a mental illness generally characterized by impairments in the perception or expression of reality, often in the context of significant social dysfunction. Many believe that damages to the developing nervous system may lay dormant until maturity and then be expressed in the symptoms of schizophrenia. Understanding disease and developing new therapies requires animal models that mimic the origins and the ultimate presentation of the clinical condition. Thus, development and characterization of new models in which hypotheses can be tested can provide insight into mechanisms of human neuropathological diseases. We have previously shown that early alterations in excitatory transmission, during critical periods of brain development, produce lasting changes which are suggestive of some of the symptoms manifested in schizophrenia. The focus of the proposed experiments is to better characterize these changes with respect to their relevance to schizophrenia. Results from these studies will offer a better understanding of the relationship between changes in perinatal glutamatergic signaling and lasting alterations in neurobehaviour and brain circuitry relevant to schizophrenia and other neurological diseases.