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Alterations of Cortical GABA Neurons and Network Oscillations in Schizophrenia

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Abstract

The hypothesis that alterations of cortical inhibitory γ-aminobutyric acid (GABA) neurons are a central element in the pathology of schizophrenia has emerged from a series of postmortem studies. How such abnormalities may contribute to the clinical features of schizophrenia has been substantially informed by a convergence with basic neuroscience studies revealing complex details of GABA neuron function in the healthy brain. Importantly, activity of the parvalbumin-containing class of GABA neurons has been linked to the production of cortical network oscillations. Furthermore, growing knowledge supports the concept that γ band oscillations (30–80 Hz) are an essential mechanism for cortical information transmission and processing. Herein we review recent studies further indicating that inhibition from parvalbumin-positive GABA neurons is necessary to produce γ oscillations in cortical circuits; provide an update on postmortem studies documenting that deficits in the expression of glutamic acid decarboxylase67, which accounts for most GABA synthesis in the cortex, are widely observed in schizophrenia; and describe studies using novel, noninvasive approaches directly assessing potential relations between alterations in GABA, oscillations, and cognitive function in schizophrenia.

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Disclosure

Dr. Lewis has received investigator-initiated research support from the Bristol-Myers Squibb Foundation, Bristol-Myers Squibb, Curidium Ltd., and Pfizer and has served as a consultant for AstraZeneca, BioLineRx, Bristol-Myers Squibb, Hoffmann-Roche, Eli Lilly and Company, Merck & Co., Neurogen Corp., and SK Life Science. No other potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Room W1651, Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15261, USA

    Guillermo Gonzalez-Burgos & David A. Lewis

  2. Department of Psychiatry, Kanazawa University, Kanazawa, Japan

    Takanori Hashimoto

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  1. Guillermo Gonzalez-Burgos
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  2. Takanori Hashimoto
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  3. David A. Lewis
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Correspondence to Guillermo Gonzalez-Burgos.

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Gonzalez-Burgos, G., Hashimoto, T. & Lewis, D.A. Alterations of Cortical GABA Neurons and Network Oscillations in Schizophrenia. Curr Psychiatry Rep 12, 335–344 (2010). https://doi.org/10.1007/s11920-010-0124-8

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