Clusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer's Disease-Reference-Cited by-同舟云学术

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

Published:2008-09-19 Issue:5896 Volume:321 Page:1686-1689
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Busche Marc Aurel¹²³⁴,Eichhoff Gerhard¹²³⁴,Adelsberger Helmuth¹²³⁴,Abramowski Dorothee¹²³⁴,Wiederhold Karl-Heinz¹²³⁴,Haass Christian¹²³⁴,Staufenbiel Matthias¹²³⁴,Konnerth Arthur¹²³⁴,Garaschuk Olga¹²³⁴

Affiliation:

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.

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 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 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference42 articles.

1. Functional activation imaging in aging and dementia

2. Positron Emission Tomography in Evaluation of Dementia

3. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease

4. Alzheimer's Disease Is a Synaptic Failure

5. Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment

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