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Science 19 September 2008:
Vol. 321. no. 5896, pp. 1686 - 1689
DOI: 10.1126/science.1162844
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Reports

Clusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer's Disease

Marc Aurel Busche,1,4 Gerhard Eichhoff,1,4 Helmuth Adelsberger,1,4 Dorothee Abramowski,2 Karl-Heinz Wiederhold,2 Christian Haass,3,4 Matthias Staufenbiel,2 Arthur Konnerth,1,4* Olga Garaschuk1,4{dagger}

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.

1 Institut für Neurowissenschaften, Technische Universität München (TUM), 80802 München, Germany.
2 Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland.
3 Adolf-Butenandt-Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig-Maximilians-Universität, 80336 München, Germany.
4 Center for Integrated Protein Science, 81377 München, Germany.

{dagger} Present address: Institute of Physiology II, Wilhelmstraße 27, 72074 Tübingen, Germany.

* To whom correspondence should be addressed. E-mail: arthur.konnerth{at}lrz.tum.de

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer's Disease.
M. I. Fonseca, R. R. Ager, S.-H. Chu, O. Yazan, S. D. Sanderson, F. M. LaFerla, S. M. Taylor, T. M. Woodruff, and A. J. Tenner (2009)
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I. Bezprozvanny (2009)
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Amyloid {beta}-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy.
R. Minkeviciene, S. Rheims, M. B. Dobszay, M. Zilberter, J. Hartikainen, L. Fulop, B. Penke, Y. Zilberter, T. Harkany, A. Pitkanen, et al. (2009)
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Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice.
K. V. Kuchibhotla, C. R. Lattarulo, B. T. Hyman, and B. J. Bacskai (2009)
Science 323, 1211-1215
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