TY - JOUR
T1 - Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease
AU - Grienberger, Christine
AU - Rochefort, Nathalie L.
AU - Adelsberger, Helmuth
AU - Henning, Horst A.
AU - Hill, Daniel N.
AU - Reichwald, Julia
AU - Staufenbiel, Matthias
AU - Konnerth, Arthur
PY - 2012
Y1 - 2012
N2 - The accumulation of amyloid-2 in the brain is an essential feature of Alzheimer's disease. However, the impact of amyloid- 2-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.
AB - The accumulation of amyloid-2 in the brain is an essential feature of Alzheimer's disease. However, the impact of amyloid- 2-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.
UR - https://www.scopus.com/pages/publications/84860304777
U2 - 10.1038/ncomms1783
DO - 10.1038/ncomms1783
M3 - Article
C2 - 22491322
AN - SCOPUS:84860304777
SN - 2041-1723
VL - 3
JO - Nature Communications
JF - Nature Communications
M1 - 774
ER -