Document Detail


NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia.
MedLine Citation:
PMID:  22245663     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: There is increasing evidence that functional deficits in schizophrenia may be driven by a reduction in the signal-to-noise ratio (SNR) and consistent timing of neural signals. This study examined the extent to which exposure to the NMDA receptor antagonists ketamine and MK801, frequently used pharmacological models of schizophrenia, recreate deficits in electrophysiological markers of disturbed brain circuits that are thought to underlie the illness. Furthermore, this study characterizes the specificity of these differences across the frequency spectrum so as to help identify the nature of selective circuit abnormalities that mediate each oscillatory response as relevant to schizophrenia.
DESIGN: Mouse EEG was recorded during exposure to repeated auditory stimuli after injection of either vehicle or drug. The dose-response relationship for each electrophysiological measure was determined for ketamine and MK-801. Time-frequency analyses were performed to assess baseline, total, and evoked power and intertrial coherence (ITC) at low (5-10 Hz) and high (35-80 Hz)-frequencies.
RESULTS: High frequency evoked and total power was decreased by MK-801 and ketamine in a dose-dependent fashion. High frequency baseline power was increased by MK-801 and ketamine in a dose-dependent fashion. Similar to evoked power, high frequency inter-trial coherence was dose-dependently decreased by both drugs. Low frequency ITC was only decreased by ketamine.
CONCLUSIONS: Both ketamine and MK-801 cause alterations in high-frequency baseline (noise), total (signal), and evoked (signal) power resulting in a loss of high frequency SNR that is thought to primarily reflect local circuit activity. These changes indicate an inappropriate increase in baseline activity, which can also be interpreted as non-task related activity. Ketamine induced a loss of intertrial coherence at low frequencies, indicating a loss of consistency in low-frequency circuit mechanisms. As a proportion of baseline power, both drugs had a relative shift from low to high frequencies, reflecting a change in the balance of brain activity from coordination of global regions to a pattern of discoordinated, autonomous local activity. These changes are consistent with a pattern of fragmented regional brain activity seen in schizophrenia.
Authors:
John A Saunders; Michael J Gandal; Steve J Siegel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-09
Journal Detail:
Title:  Neurobiology of disease     Volume:  46     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-12     Completed Date:  2012-11-20     Revised Date:  2014-10-19    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  93-100     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Evoked Potentials / drug effects*,  physiology
Excitatory Amino Acid Antagonists / toxicity*
Male
Mice
Mice, Inbred C57BL
Neural Pathways / drug effects,  metabolism,  physiopathology
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*,  metabolism
Schizophrenia / chemically induced*,  metabolism,  physiopathology*
Grant Support
ID/Acronym/Agency:
5R01DA023210/DA/NIDA NIH HHS; P50 MH064045/MH/NIMH NIH HHS; P50 MH096891/MH/NIMH NIH HHS; R01 DA023210/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate
Comments/Corrections

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