title: Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease.
abstract: The accumulation of amyloid-β in the brain is an essential feature of Alzheimer's disease. However, the impact of amyloid-β-accumulation on neuronal dysfunction on the single cell level in vivo is poorly understood. Here we investigate the progression of amyloid-β load in relation to neuronal dysfunction in the visual system of the APP23×PS45 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-β 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-β-load.
authors.affiliation: Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Biedersteinerstr. 29, 80802 Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Grienberger
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Rochefort
authors.forename: Helmuth
authors.initials: H
authors.lastname: Adelsberger
authors.forename: Horst A
authors.initials: HA
authors.lastname: Henning
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Hill
authors.forename: Julia
authors.initials: J
authors.lastname: Reichwald
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Arthur
authors.initials: A
authors.lastname: Konnerth
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides