Grant: Operating Grant

The idea of schizophrenia typically conjures up images of people who hear voices, see visions and have delusional beliefs. However, clinicians have long recognized that cognitive dysfunction is actually one of the most fundamental and debilitating aspects of the disorder. Numerous brain abnormalities are believed to underlie these symptoms. Among these, studies of the brains of schizophrenic subjects have identified dysfunction of a brain chemical termed GABA as potentially being a major cause of the cognitive symptoms. GABA is the primary inhibitory neurotransmitter in the brain that is important for filtering out extraneous information and helps to synchronize the activity of groups of neurons in the frontal lobes (also referred to as the prefrontal cortex). In schizophrenia, GABA transmission appears to be reduced, resulting in a hyperactive or 'noisy' cortex that may impair attention and other cognitive functions that are regulated by the frontal lobes. However, our understanding of exactly how prefrontal cortical GABA may regulate these different aspects of cognition is sparse. Our proposed experiments are designed to thoroughly investigate how GABA transmission within the prefrontal cortex regulates a variety of cognitive functions known to be impaired in schizophrenia, using rats as a model system. Other studies will investigate how a noisy cortex may interfere with information processing in other subcortical regions. These studies will provide important new insight into how hyperactivity within the frontal lobes may be an underlying cause of the cognitive abnormalities present in schizophrenia. In turn, this information may facilitate the development of novel drug therapies intended to alleviate these cognitive deficits.