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Amyloid-Beta Mediates Homeostatic Synaptic Plasticity

Authors
  • Galanis, Christos
  • Fellenz, Meike
  • Becker, Denise
  • Bold, Charlotte
  • Lichtenthaler, Stefan F.
  • Müller, Ulrike C.
  • Deller, Thomas
  • Vlachos, Andreas
Type
Published Article
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Publication Date
Jun 16, 2021
Volume
41
Issue
24
Pages
5157–5172
Identifiers
DOI: 10.1523/JNEUROSCI.1820-20.2021
PMID: 33926999
PMCID: PMC8211553
Source
PubMed Central
Keywords
Disciplines
  • Research Articles
  • Development/Plasticity/Repair
License
Unknown

Abstract

The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures prepared from APP −/− mice of both sexes. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β and not by APPsα, and it is neither observed in APP +/+ tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased amyloid-β levels.

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