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Disease-associated mutations in the tau-encoding MAPT gene have enabled the generation of transgenic mouse models that recapitulate aspects of human neurodegenerative diseases, including tau hyperphosphorylation and neurofibrillary tangle formation. Here, we characterized the effects of transgenic P301S mutant human tau expression on neuronal network function in the murine hippocampus. Onset of progressive spatial learning deficits in P301S tau transgenic TAU58\/2 mice were paralleled by long-term potentiation deficits and neuronal network aberrations during electrophysiological and EEG recordings. Gene-expression profiling just prior to onset of apparent deficits in TAU58\/2 mice revealed a signature of immediate early genes that is consistent with neuronal network hypersynchronicity. We found that the increased immediate early gene activity was confined to neurons harbouring tau pathology, providing a cellular link between aberrant tau and network dysfunction. Taken together, our data suggest that tau pathology drives neuronal network dysfunction through hyperexcitation of individual, pathology-harbouring neurons, thereby contributing to memory deficits.<\/jats:p>","DOI":"10.1093\/brain\/awaa133","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T11:10:54Z","timestamp":1586862654000},"page":"1889-1904","source":"Crossref","is-referenced-by-count":19,"title":["Onset of hippocampal network aberration and memory deficits in P301S tau mice are associated with an early gene signature"],"prefix":"10.1093","volume":"143","author":[{"given":"Magdalena","family":"Przybyla","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"van Eersel","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"van Hummel","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"van der Hoven","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-3993","authenticated-orcid":false,"given":"Miheer","family":"Sabale","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Harasta","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Genome Informatics at Molecular Health GmbH, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Gajwani","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"},{"name":"Faculty of Medicine, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8833-2728","authenticated-orcid":false,"given":"Emmanuel","family":"Prikas","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mueller","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire H","family":"Stevens","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Bioscience, University of Wollongong and the Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Power","sequence":"first","affiliation":[{"name":"Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D","family":"Housley","sequence":"first","affiliation":[{"name":"Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Karl","sequence":"first","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kassiou","sequence":"first","affiliation":[{"name":"School of Chemistry, University of Sydney, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazi D","family":"Ke","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Ittner","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-3825","authenticated-orcid":false,"given":"Lars M","family":"Ittner","sequence":"first","affiliation":[{"name":"Dementia Research Centre and Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, 2109, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"2020061607533280500_awaa133-B1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.neubiorev.2017.01.004","article-title":"Mouse models of frontotemporal dementia: a comparison of phenotypes with clinical symptomatology","volume":"74","author":"Ahmed","year":"2017","journal-title":"Neurosci Biobehav 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