The idea of schizophrenia typically conjures up images of people who hear voices, see visions and have delusional beliefs. However, clinicians have long recognized cognitive dysfunction as one of the most fundamental and debilitating aspects of the disorder.  Among the numerous brain abnormalities thought to underlie these symptoms, perturbations of the inhibitory neurotransmitter GABA within the frontal lobes are some of the most reliable alterations observed in the post-mortem brains of schizophrenic patients. These alterations may result in a hyperactive or ‘noisy’ cortex that may impair attention and other cognitive functions regulated by the frontal lobes.  However, our understanding of exactly how prefrontal cortical GABA may regulate these different aspects of cognition is sparse.  To better understand how these pathophysiological alterations may contribute to schizophrenia symptomology, work by our group has investigated how GABA transmission within the prefrontal cortex of rodents regulates a variety of cognitive, emotional and motivational functions known to be impaired in schizophrenia, using translational assays similar to those used with human patients.  Our findings indicate that reducing prefrontal GABA transmission recapitulates many of the cognitive, behavioural and dopaminergic abnormalities associated with schizophrenia, suggesting that dysfunction within this system may be a major contributing factor to variety of symptoms of the disorder.

Learning objectives

-Describe the evidence for dysfunction of inhibitory (GABAergic) transmission in schizophrenia

-Explain how prefrontal cortical GABA transmission regulates a variety of cognitive and executive functions

-Explore how translational research with animals can elucidate the neuropathology underlying mental illness