Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease

Science 321(5896): 1686-9

Authors/Editors: Busche MA
Eichhoff G
Adelsberger H
Abramowski D
Wiederhold KH
Haass C
Staufenbiel M
Konnerth A
Garaschuk O
Publication Date: 2008
Type of Publication: Journal Article
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.

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