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

Marc Aurel Busche; Gerhard Eichhoff; Helmuth Adelsberger; Dorothee Abramowski; Karl Heinz Wiederhold; Christian Haass; Matthias Staufenbiel; Arthur Konnerth; Olga Garaschuk

doi:10.1126/science.1162844

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

Marc Aurel Busche, Gerhard Eichhoff, Helmuth Adelsberger, Dorothee Abramowski, Karl Heinz Wiederhold, Christian Haass, Matthias Staufenbiel, Arthur Konnerth, Olga Garaschuk

Former organisations of Medicine and Health

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844 Scopus citations

Abstract

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 β-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.

Original language	English
Pages (from-to)	1686-1689
Number of pages	4
Journal	Science
Volume	321
Issue number	5896
DOIs	https://doi.org/10.1126/science.1162844
State	Published - 19 Sep 2008

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abstract = "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 β-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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AU - Busche, Marc Aurel

AU - Eichhoff, Gerhard

AU - Adelsberger, Helmuth

AU - Abramowski, Dorothee

AU - Wiederhold, Karl Heinz

AU - Haass, Christian

AU - Staufenbiel, Matthias

AU - Konnerth, Arthur

AU - Garaschuk, Olga

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N2 - 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 β-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.

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

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