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dc.contributor.authorMurphy, K. P. S. J.
dc.contributor.authorCarter, R. J.
dc.contributor.authorMangiarini, L.
dc.contributor.authorMahal, A.
dc.contributor.authorBates, G. P.
dc.contributor.authorDunnett, S.B.
dc.contributor.authorMorton, A. J.
dc.contributor.authorLione, Lisa
dc.date.accessioned2013-07-03T15:02:11Z
dc.date.available2013-07-03T15:02:11Z
dc.date.issued2000-07-01
dc.identifier.citationMurphy , K P S J , Carter , R J , Mangiarini , L , Mahal , A , Bates , G P , Dunnett , S B , Morton , A J & Lione , L 2000 , ' Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation ' , Journal of Neuroscience , vol. 20 , no. 13 , pp. 5115-5123 .
dc.identifier.issn0270-6474
dc.identifier.otherPURE: 670410
dc.identifier.otherPURE UUID: 28ea9a06-27e6-4828-bbf6-c75e494518fe
dc.identifier.otherWOS: 000087816300037
dc.identifier.otherScopus: 0034234519
dc.identifier.urihttp://hdl.handle.net/2299/11078
dc.description.abstractHuntington's disease (HD) is an autosomal dominant progressive and fatal neurodegenerative brain disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the gene. Presymptomatic Huntington's disease patients often exhibit cognitive deficits before the onset of classical symptoms. To investigate the possibility that changes in synaptic plasticity might underlie cognitive impairment in HD, we examined hippocampal synaptic plasticity and spatial cognition in a transgenic mouse (R6/2 line) expressing exon 1 of the human Huntington's disease gene containing an expanded CAG repeat. This mouse exhibits a progressive and fatal neurological phenotype that resembles Huntington's disease. We report that R6/2 mice show marked alterations in synaptic plasticity at both CA1 and dentate granule cell synapses, and impaired spatial cognitive performance in the Morris water maze. The changes in hippocampal plasticity were age dependent, appearing at CA1 synapses several weeks before they were observed in the dentate gyrus. Deficits in synaptic plasticity at CA1 synapses occurred before an overt phenotype. This suggests that altered synaptic plasticity contributes to the presymptomatic changes in cognition reported in human carriers of the Huntington' disease gene. The temporal and regional changes in synaptic plasticity within the hippocampus mirror the appearance of neuronal intranuclear inclusions, suggesting a relationship between polyglutamine aggregation and dysfunction.en
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofJournal of Neuroscience
dc.subjectHuntington's disease
dc.subjectlong-term potentiation
dc.subjectlong-term depression
dc.subjecthippocampus
dc.subjectcognition
dc.subjectintranuclear inclusions
dc.subjectNMDA receptor
dc.subjectLONG-TERM POTENTIATION
dc.subjectNEURONAL INTRANUCLEAR INCLUSIONS
dc.subjectAMYLOID PRECURSOR PROTEIN
dc.subjectEXPANDED CAG REPEAT
dc.subjectMOUSE MODEL
dc.subjectBEHAVIORAL ABNORMALITIES
dc.subjectGLUTAMATE EXOCYTOSIS
dc.subjectMUTANT HUNTINGTIN
dc.subjectDIABETIC RATS
dc.subjectAREA CA1
dc.titleAbnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutationen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionDiabetic neuropathies
dc.contributor.institutionTRP Ion channels
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstyperestrictedAccess


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