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

被引：888

作者：

Busche, Marc Aurel ^{[1
,4
]}

Eichhoff, Gerhard ^{[1
,4
]}

Adelsberger, Helmuth ^{[1
,4
]}

Abramowski, Dorothee ^{[2
]}

Wiederhold, Karl-Heinz ^{[2
]}

Haass, Christian ^{[3
,4
]}

Staufenbiel, Matthias ^{[2
]}

Konnerth, Arthur ^{[1
,4
]}

Garaschuk, Olga ^{[1
,4
]}

机构：

[1] Tech Univ Munich, Inst Neurowissensch, D-80802 Munich, Germany

[2] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland

[3] Univ Munich, Dept Biochem, Lab Neurodegenerat Dis Res, Adolf Butenandt Inst, D-80336 Munich, Germany

[4] Ctr Integrated Prot Sci, D-81377 Munich, Germany

来源：

SCIENCE | 2008年 / 321卷 / 5896期

关键词：

D O I：

10.1126/science.1162844

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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 Ca(2+) 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 Ca(2+) 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.

引用

页码：1686 / 1689

页数：4

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