Document Detail

NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia.
MedLine Citation:
PMID:  22245663     Owner:  NLM     Status:  MEDLINE    
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.
John A Saunders; Michael J Gandal; Steve J Siegel
Related Documents :
17419073 - Variability of successive contractions subtracted from unfused tetanus of fast and slow...
12932423 - Changes in landing biomechanics during a fatiguing landing activity.
19535483 - Control of stepping velocity in the stick insect carausius morosus.
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Disease Models, Animal
Evoked Potentials / drug effects*,  physiology
Excitatory Amino Acid Antagonists / toxicity*
Mice, Inbred C57BL
Neural Pathways / drug effects,  metabolism,  physiopathology
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*,  metabolism
Schizophrenia / chemically induced*,  metabolism,  physiopathology*
Grant Support
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal o...
Next Document:  Body Mass Index Increases Risk for Colorectal Adenomas, Based on Meta-Analysis.