title: GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.
abstract: Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.
authors: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. gburgos@pitt.edu
authors: Guillermo
authors: G
authors: Gonzalez-Burgos
authors: Kenneth N
authors: KN
authors: Fish
authors: David A
authors: DA
authors: Lewis
mesh_terms: D000818:Animals; D001683:Biological Clocks; D002540:Cerebral Cortex / Q000254:growth & development / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D003344:Cortical Synchronization / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008959:Models, Neurological; D008960:Models, Psychological; D009415:Nerve Net / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D010320:Parvalbumins / Q000032:analysis; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D010320:Parvalbumins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid