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ReportsClusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer's Disease![]()
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.
* To whom correspondence should be addressed. E-mail: arthur.konnerth{at}lrz.tum.de
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Science. ISSN 0036-8075 (print), 1095-9203 (online)