Grant: Operating Grant

Schizophrenia is associated with three main classes of symptoms, termed positive, negative and cognitive symptoms. Positive symptoms such as hallucinations and delusions are well treated by modern antipsychotic medications, as are negative symptoms to varying degrees. On the other hand, cognitive symptoms are not. Cognitive symptoms include deficits in working memory, attention and response flexibility and may be a core feature of the disease emerging before other symptom classes. It is now well established that dysfunction of the prefrontal cortex (PFC) is a key feature of the cognitive symptoms in schizophrenia. A critical question therefore is what happens to networks of cells in the PFC that could lead to cognitive symptoms? While current methodologies prevent addressing questions of cellular mechanisms in humans, there are numerous well-established rodent models of schizophrenia, including neonatal ventral hippocampal model. By recording up to hundreds of neurons simultaneously in behaving rats, we hope to understand what happens to networks of cells in the PFC when "schizophrenic" animals fail on cognitive tasks similar to those that schizophrenic patients fail on. We also hope to determine what changes in the networks are, and what changes are not affected by administration of medications used in patients. It is hoped that this approach will provide critical new insights into cellular basis of cognitive dysfunction in schizophrenia and perhaps lead to treatments for these currently untreatable symptoms.