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

Overview

Journal Science

Specialty Science

Date 2008 Sep 20

PMID 18802001

Citations 567

Authors

Marc Aurel Busche

Gerhard Eichhoff

Helmuth Adelsberger

Dorothee Abramowski

Karl-Heinz Wiederhold

Christian Haass

Matthias Staufenbiel

Arthur Konnerth

Olga Garaschuk

Affiliations

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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 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.

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