Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease

Christine Grienberger, Nathalie L. Rochefort, Helmuth Adelsberger, Horst A. Henning, Daniel N. Hill, Julia Reichwald, Matthias Staufenbiel, Arthur Konnerth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The accumulation of amyloid-beta in the brain is an essential feature of Alzheimer's disease. However, the impact of amyloid-beta-accumulation on neuronal dysfunction on the single cell level in vivo is poorly understood. Here we investigate the progression of amyloid-beta load in relation to neuronal dysfunction in the visual system of the APP23xPS45 mouse model of Alzheimer's disease. Using in vivo two-photon calcium imaging in the visual cortex, we demonstrate that a progressive deterioration of neuronal tuning for the orientation of visual stimuli occurs in parallel with the age-dependent increase of the amyloid-beta load. Importantly, we find this deterioration only in neurons that are hyperactive during spontaneous activity. This impairment of visual cortical circuit function also correlates with pronounced deficits in visual-pattern discrimination. Together, our results identify distinct stages of decline in sensory cortical performance in vivo as a function of the increased amyloid-beta-load.

Original languageEnglish
Article number774
Number of pages10
JournalNature Communications
Volume3
DOIs
Publication statusPublished - Apr 2012

Keywords

  • AGE-RELATED-CHANGES
  • PROTEIN TRANSGENIC MICE
  • MILD COGNITIVE IMPAIRMENT
  • NETWORK DYSFUNCTION
  • CORTICAL-NEURONS
  • CAT VISUAL-CORTEX
  • A-BETA
  • SYNAPTIC PLASTICITY
  • MOUSE MODEL
  • AMYLOID-BETA PLAQUES

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