Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs

Jesse Wood, Yunbok Kim, Bita Moghaddam

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas theNMDAreceptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spike-rate and local field potential power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease.

Original languageEnglish (US)
Pages (from-to)3022-3031
Number of pages10
JournalJournal of Neuroscience
Volume32
Issue number9
DOIs
StatePublished - Feb 29 2012
Externally publishedYes

Fingerprint

Prefrontal Cortex
Pharmaceutical Preparations
Hallucinogens
Schizophrenia
Population
Animal Disease Models
Pyramidal Cells
Amphetamine
N-Methyl-D-Aspartate Receptors
Cognition
Biomarkers
Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs. / Wood, Jesse; Kim, Yunbok; Moghaddam, Bita.

In: Journal of Neuroscience, Vol. 32, No. 9, 29.02.2012, p. 3022-3031.

Research output: Contribution to journalArticle

@article{dbdf3ec91c4542c08cf08ac12f725a6f,
title = "Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs",
abstract = "In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas theNMDAreceptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spike-rate and local field potential power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease.",
author = "Jesse Wood and Yunbok Kim and Bita Moghaddam",
year = "2012",
month = "2",
day = "29",
doi = "10.1523/JNEUROSCI.6377-11.2012",
language = "English (US)",
volume = "32",
pages = "3022--3031",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "9",

}

TY - JOUR

T1 - Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs

AU - Wood, Jesse

AU - Kim, Yunbok

AU - Moghaddam, Bita

PY - 2012/2/29

Y1 - 2012/2/29

N2 - In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas theNMDAreceptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spike-rate and local field potential power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease.

AB - In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas theNMDAreceptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spike-rate and local field potential power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease.

UR - http://www.scopus.com/inward/record.url?scp=84863297737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863297737&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.6377-11.2012

DO - 10.1523/JNEUROSCI.6377-11.2012

M3 - Article

C2 - 22378875

AN - SCOPUS:84863297737

VL - 32

SP - 3022

EP - 3031

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 9

ER -