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

ArticleinScience 321(5896):1686-9 · October 2008with22 Reads
Impact Factor: 33.61 · DOI: 10.1126/science.1162844 · Source: PubMed

    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.