Rescue of long-range circuit dysfunction in Alzheimer's disease models

Marc Aurel Busche*, Maja Kekuš, Helmuth Adelsberger, Takahiro Noda, Hans Förstl, Israel Nelken, Arthur Konnerth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Alzheimer's disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non-rapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. There is increasing evidence that sleep is often impaired in AD, but it is unclear whether this impairment is directly related to amyloid-β (Aβ) pathology. Here we demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of AD amyloidosis. Most notably, our results reveal an Aβ-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding that the impairment can be rescued by enhancing GABA A ergic inhibition identifies a synaptic mechanism underlying Aβ-dependent large-scale circuit dysfunction.

Original languageAmerican English
Pages (from-to)1623-1630
Number of pages8
JournalNature Neuroscience
Volume18
Issue number11
DOIs
StatePublished - 1 Nov 2015

Bibliographical note

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© 2015 Nature America, Inc.

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