Article thumbnail

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

By Marc Aurel Busche, Helmuth Adelsberger, Maja Kekus, Hans Förstl, Israel Nelken and Arthur Konnerth

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

Year: 2015
DOI identifier: 10.1038/nn.4137
OAI identifier: oai:oak.novartis.com:21062
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://oak.novartis.com/21062... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.