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However, it remains uncertain whether the<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>abnormalities are actually caused by<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine whether<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>can cause neural network abnormalities, we performed<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>recordings and analyzed the expression of neuronal activity\u2010dependent gene products in<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>transgenic mice. We also carried out comparative analyses in humans with<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that neuronal expression of<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>in transgenic mice causes a left shift in spectral power that closely resembles the<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>slowing observed in<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>patients. Surprisingly,<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>mice also had seizures and showed molecular hippocampal alterations indicative of aberrant network excitability, including calbindin depletion in the dentate gyrus. In postmortem brain tissues from<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>patients, we found reduced levels of calbindin<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>in the dentate gyrus. Furthermore, nearly one quarter of<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>patients showed myoclonus, a clinical sign of aberrant network excitability that was associated with an earlier age of onset of cognitive impairments. In<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>mice, partial suppression of epileptiform activity did not alter their shift in spectral power. Furthermore, epileptiform activity in human amyloid precursor protein transgenic mice was not associated with a left shift in spectral power.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We conclude that neuronal accumulation of<jats:styled-content style=\"fixed-case\">SYN<\/jats:styled-content>slows brain oscillations and, in parallel, causes aberrant network excitability that can escalate into seizure activity. The potential role of aberrant network excitability in<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>merits further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.257","type":"journal-article","created":{"date-parts":[[2015,10,17]],"date-time":"2015-10-17T12:37:09Z","timestamp":1445085429000},"page":"1012-1028","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Network dysfunction in<i>\u03b1<\/i>\u2010synuclein transgenic mice and human Lewy body dementia"],"prefix":"10.1002","volume":"2","author":[{"given":"Meaghan","family":"Morris","sequence":"first","affiliation":[{"name":"Gladstone Institute of Neurological Disease San Francisco California 94158"},{"name":"Biochemistry, Cellular and Molecular Biology Graduate Program Department of Biological Chemistry The Johns Hopkins University School of Medicine Baltimore Maryland 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