| Rapid reversal of impaired inhibitory and excitatory transmission but not spine dysgenesis in a mouse model of mental retardation. | |
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MedLine Citation:
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PMID: 22124149 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Intellectual disability affects 2-3% of the population: those due to mutations of the X-chromosome are a major cause of moderate to severe cases (1.8/1000 males). Established theories ascribe the cellular aetiology of intellectual disability to malformations of dendritic spines. Recent work has identified changes in synaptic physiology in some experimental models. Here, we investigated the pathophysiology of a mouse model of intellectual disability using electrophysiological recordings combined with confocal imaging of dentate gyrus granule neurons. Lack of oligophrenin-1 resulted in reductions in dendritic tree complexity and dendritic spine density and also a reduction in the readily releasable pool and vesicle recycling which impaired the efficiency of both excitatory and inhibitory synaptic transmission. Acute inhibition of the downstream signalling pathway of oligophrenin-1 fully reversed the functional changes in synaptic transmission but not the dendritic abnormalities. The impaired inhibitory (as well as excitatory) synaptic transmission at frequencies associated with cognitive function suggests a cellular mechanism for the intellectual disability, because cortical oscillations associated with cognition normally depend on inhibitory neurons firing on every cycle. |
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Authors:
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Andrew D Powell; Kalbinder K Gill; Pierre-Philippe Saintot; Premysl Jiruska; Jamel Chelly; Pierre Billuart; John Gr Jefferys |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-28 |
Journal Detail:
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Title: The Journal of physiology Volume: - ISSN: 1469-7793 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Birmingham; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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