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Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions

Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnan...

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Autores principales: Dickerson, Desiree D., Bilkey, David K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873515/
https://www.ncbi.nlm.nih.gov/pubmed/24409130
http://dx.doi.org/10.3389/fnbeh.2013.00217
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author Dickerson, Desiree D.
Bilkey, David K.
author_facet Dickerson, Desiree D.
Bilkey, David K.
author_sort Dickerson, Desiree D.
collection PubMed
description Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes.
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spelling pubmed-38735152014-01-09 Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions Dickerson, Desiree D. Bilkey, David K. Front Behav Neurosci Neuroscience Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes. Frontiers Media S.A. 2013-12-27 /pmc/articles/PMC3873515/ /pubmed/24409130 http://dx.doi.org/10.3389/fnbeh.2013.00217 Text en Copyright © 2013 Dickerson and Bilkey. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Dickerson, Desiree D.
Bilkey, David K.
Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title_full Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title_fullStr Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title_full_unstemmed Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title_short Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
title_sort aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873515/
https://www.ncbi.nlm.nih.gov/pubmed/24409130
http://dx.doi.org/10.3389/fnbeh.2013.00217
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