Cited by 1,125Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

Busche, Marc Aurel, Eichhoff, Gerhard, Adelsberger, Helmuth, Abramowski, Dorothee, Wiederhold, Karl-Heinz, Haass, Christian, Staufenbiel, Matthias, Konnerth, Arthur +1 more·2008·Science

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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Crossref · 10.1126/science.1162844

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Authors
Busche, M. A., Eichhoff, G., Adelsberger, H., Abramowski, D., Wiederhold, K.-H., Haass, C., Staufenbiel, M., Konnerth, A., & Garaschuk, O.
Affiliations
  • Center for Integrated Protein Science Munich (DE)
  • Institut für Neurowissenschaften, Technische Universität München (TUM), 80802 München, Germany.
Corresponding author
  • Konnerth, Arthur
  • Garaschuk, Olga
Venue
Science
Published
2008-09-19
Volume
321
Issue
5896
Pages
1686-1689
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2048685634
Cited by
1,125
References
40
Citations by year
2026: 68 · 2025: 84 · 2024: 100 · 2023: 85 · 2022: 96 · 2021: 100 · 2020: 80 · 2019: 57 · 2018: 56 · 2017: 50 · 2016: 55 · 2015: 41 · 2014: 53 · 2013: 36 · 2012: 45
FWCI
26.71
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid plaques, neuronal hyperactivity, spontaneous calcium transients, synaptic inhibition, mouse models of Alzheimer's disease, two-photon calcium imaging
MeSH terms
Alzheimer Disease, Animals, Calcium, Cerebral Cortex, Disease Models, Animal, Memory, Mice, Transgenic, Nerve Net, Neurons, Peptide Fragments, Synapses, Amyloid beta-Peptides, Maze Learning, Calcium Signaling, Mice, Plaque, Amyloid

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