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Breakdown of slow-wave oscilliations in mouse modles of Alzheimer's disease

Busche, Marc Aurel and Adelsberger, Helmuth and Kekus, Maja and Förstl, Hans and Nelken, Israel and Konnerth, Arthur (2015) Breakdown of slow-wave oscilliations in mouse modles of Alzheimer's disease. Nature Neuroscience.

Abstract

Alzheimer´s disease (AD) causes devastating impairments in long-term memory1. In the healthy brain, memory consolidation crucially depends on slow-wave oscillations2-4 that are generated during sleep5 in interconnected large-scale neuronal networks, including the neocortex and the hippocampus6-8. Functional magnetic resonance imaging (fMRI) studies indicate that in AD patients, the functional connectivity between distant brain regions is massively impaired9-11. However, the consequences of these impairments for temporally coordinated brain activities, such as slow-wave oscillations, are unknown. Here, we implemented a method of large-scale brain calcium fluorescence imaging to analyze slow-wave activity across widely distributed neuronal networks in the neocortex and hippocampus of transgenic mouse models of AD in vivo. The results demonstrate a strong impairment of slow-wave activity, with a severe breakdown of its long-range coherence within the cortex as well as between cortex and hippocampus of transgenic mice. Similar impairments can be induced in wild-type mice by direct application of exogenous amyloid-ß (Aß) peptides. The coherence of cortical activity can be restored, both in transgenic and in Aß-treated animals, by enhancing GABAAergic inhibition with benzodiazepines. Together, our results reveal a causal link between pathologically high levels of Aß, neuronal disinhibition and the breakdown of slow-wave activity in the diseased brain.

Item Type: Article
Date Deposited: 15 Oct 2015 23:45
Last Modified: 15 Oct 2015 23:45
URI: https://oak.novartis.com/id/eprint/21062

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