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Science 321 (5896): 1686-1689

Copyright © 2008 by the American Association for the Advancement of Science

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}

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.

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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