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Region-specific changes in gamma and beta2 rhythms in NMDA receptor dysfunction models of schizophrenia

Lookup NU author(s): Dr Anita Roopun, Professor Mark Cunningham, Dr Claudia RaccaORCiD, Dr Kai Alter, Professor Miles Whittington


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Cognitive disruption in schizophrenia is associated with altered patterns of spatiotemporal interaction associated with multiple electroencephalogram (EEG) frequency bands in cortex. In particular, changes in the generation of gamma (30-80 Hz) and beta2 (20-29 Hz) rhythms correlate with observed deficits in communication between different cortical areas. Aspects of these changes can be reproduced in animal models, most notably those involving acute or chronic reduction in glutamatergic synaptic communication mediated by N-methyl D-aspartate (NMDA) receptors. In vitro electrophysiological and immunocytochemical approaches afforded by such animal models continue to reveal a great deal about the mechanisms underlying EEG rhythm generation and are beginning to uncover which basic molecular, cellular, and network phenomena may underlie their disruption in schizophrenia. Here we briefly review the evidence for changes in gamma-aminobutyric acidergic (GABAergic) and glutamatergic function and address the problem of region specificity of changes with quantitative comparisons of effects of ketamine on gamma and beta2 rhythms in vitro. We conclude, from available evidence, that many observed changes in markers for GABAergic function in schizophrenia may be secondary to deficits in NMDA receptor-mediated excitatory synaptic activity. Furthermore, the broad range of changes in cortical dynamics seen in schizophrenia-with contrasting effects seen in different brain regions and for different frequency bands-may be more directly attributable to underlying deficits in glutamatergic neuronal communication rather than GABAergic inhibition alone.

Publication metadata

Author(s): Roopun AK, Cunningham MO, Racca C, Alter K, Traub RD, Whittington MA

Publication type: Article

Publication status: Published

Journal: Schizophrenia Bulletin

Year: 2008

Volume: 34

Issue: 5

Pages: 962-973

ISSN (print): 0586-7614

ISSN (electronic): 1745-1701

Publisher: Oxford University Press


DOI: 10.1093/schbul/sbn059


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Funder referenceFunder name
Medical Research Council UK
Lena Teague Bequest
SROINS044133-04National Institutes of Health