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Article: The pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletion

TitleThe pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletion
Authors
Issue Date2013
PublisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org
Citation
Journal of Neuroscience, 2013, v. 33 n. 37, p. 14825-14839 How to Cite?
AbstractWe used a mouse model of the schizophrenia-predisposing 22q11.2 microdeletion to evaluate how this genetic lesion affects cortical neural circuits at the synaptic, cellular, and molecular levels. Guided by cognitive deficits, we demonstrated that mutant mice display robust deficits in high-frequency synaptic transmission and short-term plasticity (synaptic depression and potentiation), as well as alterations in long-term plasticity and dendritic spine stability. Apart from previously reported reduction in dendritic complexity of layer 5 pyramidal neurons, altered synaptic plasticity occurs in the context of relatively circumscribed and often subtle cytoarchitectural changes in neuronal density and inhibitory neuron numbers. We confirmed the pronounced DiGeorge critical region 8 (Dgcr8)-dependent deficits in primary micro-RNA processing and identified additional changes in gene expression and RNA splicing that may underlie the effects of this mutation. Reduction in Dgcr8 levels appears to be a major driver of altered short-term synaptic plasticity in prefrontal cortex and working memory but not of long-term plasticity and cytoarchitecture. Our findings inform the cortical synaptic and neuronal mechanisms of working memory impairment in the context of psychiatric disorders. They also provide insight into the link between micro-RNA dysregulation and genetic liability to schizophrenia and cognitive dysfunction.
Persistent Identifierhttp://hdl.handle.net/10722/196731
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 2.321
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFénelon, K-
dc.contributor.authorXu, B-
dc.contributor.authorLai, SW-
dc.contributor.authorMukai, J-
dc.contributor.authorMarkx, S-
dc.contributor.authorStark, KL-
dc.contributor.authorHsu, PK-
dc.contributor.authorGan, WB-
dc.contributor.authorFischbach, GD-
dc.contributor.authorMacdermott, AB-
dc.contributor.authorKarayiorgou, M-
dc.contributor.authorGogos, JA-
dc.date.accessioned2014-04-25T03:29:10Z-
dc.date.available2014-04-25T03:29:10Z-
dc.date.issued2013-
dc.identifier.citationJournal of Neuroscience, 2013, v. 33 n. 37, p. 14825-14839-
dc.identifier.issn0270-6474-
dc.identifier.urihttp://hdl.handle.net/10722/196731-
dc.description.abstractWe used a mouse model of the schizophrenia-predisposing 22q11.2 microdeletion to evaluate how this genetic lesion affects cortical neural circuits at the synaptic, cellular, and molecular levels. Guided by cognitive deficits, we demonstrated that mutant mice display robust deficits in high-frequency synaptic transmission and short-term plasticity (synaptic depression and potentiation), as well as alterations in long-term plasticity and dendritic spine stability. Apart from previously reported reduction in dendritic complexity of layer 5 pyramidal neurons, altered synaptic plasticity occurs in the context of relatively circumscribed and often subtle cytoarchitectural changes in neuronal density and inhibitory neuron numbers. We confirmed the pronounced DiGeorge critical region 8 (Dgcr8)-dependent deficits in primary micro-RNA processing and identified additional changes in gene expression and RNA splicing that may underlie the effects of this mutation. Reduction in Dgcr8 levels appears to be a major driver of altered short-term synaptic plasticity in prefrontal cortex and working memory but not of long-term plasticity and cytoarchitecture. Our findings inform the cortical synaptic and neuronal mechanisms of working memory impairment in the context of psychiatric disorders. They also provide insight into the link between micro-RNA dysregulation and genetic liability to schizophrenia and cognitive dysfunction.-
dc.languageeng-
dc.publisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org-
dc.relation.ispartofJournal of Neuroscience-
dc.rightsJournal of Neuroscience. Copyright © Society for Neuroscience.-
dc.subject.meshDiGeorge Syndrome - complications - genetics - pathology-
dc.subject.meshLong-Term Potentiation - genetics-
dc.subject.meshLong-Term Synaptic Depression - genetics-
dc.subject.meshNeurons - pathology - physiology-
dc.subject.meshPrefrontal Cortex - pathology-
dc.titleThe pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletionen_US
dc.typeArticleen_US
dc.identifier.emailLai, SW: coraswl@hku.hk-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1523/JNEUROSCI.1611-13.2013-
dc.identifier.pmid24027283-
dc.identifier.pmcidPMC3771024-
dc.identifier.scopuseid_2-s2.0-84883736235-
dc.identifier.hkuros240574-
dc.identifier.volume33-
dc.identifier.issue37-
dc.identifier.spage14825-
dc.identifier.epage14839-
dc.identifier.isiWOS:000324316200021-
dc.publisher.placeUnited States-
dc.identifier.issnl0270-6474-

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