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Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation
BACKGROUND: The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC). RESULTS: This study used a comput...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387163/ https://www.ncbi.nlm.nih.gov/pubmed/18439259 http://dx.doi.org/10.1186/1471-2202-9-41 |
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author | Tanaka, Shoji |
author_facet | Tanaka, Shoji |
author_sort | Tanaka, Shoji |
collection | PubMed |
description | BACKGROUND: The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC). RESULTS: This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged. CONCLUSION: The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerability to psychosis by (i) producing the hyperactive mode of the PFC with hyperdopaminergic neurotransmission by dysfunctional chandelier cells and (ii) increasing the probability of the transition to the hyperactive mode from the conventional inverted-U mode by dysfunctional GABAergic interneurons. |
format | Text |
id | pubmed-2387163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-23871632008-05-20 Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation Tanaka, Shoji BMC Neurosci Research Article BACKGROUND: The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC). RESULTS: This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged. CONCLUSION: The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerability to psychosis by (i) producing the hyperactive mode of the PFC with hyperdopaminergic neurotransmission by dysfunctional chandelier cells and (ii) increasing the probability of the transition to the hyperactive mode from the conventional inverted-U mode by dysfunctional GABAergic interneurons. BioMed Central 2008-04-25 /pmc/articles/PMC2387163/ /pubmed/18439259 http://dx.doi.org/10.1186/1471-2202-9-41 Text en Copyright © 2008 Tanaka; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tanaka, Shoji Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title | Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title_full | Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title_fullStr | Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title_full_unstemmed | Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title_short | Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
title_sort | dysfunctional gabaergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387163/ https://www.ncbi.nlm.nih.gov/pubmed/18439259 http://dx.doi.org/10.1186/1471-2202-9-41 |
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