Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The goal of our project is to determine the role of two candidate schizophrenia susceptibility genes, DTNBP1 (Dystobrevin-binding protein 1/Dysbindin1) and DISC1 (Disrupted-in-schizophrenia 1), in the disruption of learning, memory, cognition, and other measures of schizophrenia disease elements which can be modeled in mice and rats. Mouse mutants have been generated for these two genes, but like other animal models, they are not perfect models of the disease state and are still being characterized. We want to determine if there is a dose-dependent effect of either of these genes on behaviour, knocking down only a single gene's transcript number in live animals. We will do this by knocking down expression of these genes in the brains of mice and possibly rats using small interfering RNAs, and then measure changes in learning, memory, cognition, and disruptions to a reflex (prepulse inhibition of the acoustic startle reflex) which is seen in people with schizophrenia and their first-degree unaffected relatives. DTNBP1 expression has been found to be decreased in the brains of individuals with schizophrenia in comparison with healthy controls, and DISC1 has been associated with a broad range of psychiatric disruptions. This research is important since people with schizophrenia suffer from reduced cognitive function for long periods during their illness, resulting in decreased social and workplace function, reducing overal function and making it difficult for these individuals to keep a job. Drugs which are currently available for the treatment of schizophrenia do not improve cognitive deficits. It is our hope that better understanding how these two target genes function in the whole animal might contribute to our understanding of the development and possibly treatment of cognitive deficits in people with schizophrenia.