| Staged decline of neuronal function in vivo in an animal model of Alzheimers disease
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| April 10, 2012
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| Grienberger C.*, Rochefort N.L.*, Adelsberger H., Henning H.A., Hill D.N., Reichwald J., Staufenbiel M. and Konnerth A. *equal contribution
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| Nature Commun. 2012 Apr 10;3:774.
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 The accumulation of amyloid-β in the brain is an essential feature of Alzheimers 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 Alzheimers 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.
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