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Clusters of Hyperactive Neurons Near Amyloid Plaques in a Mouse Model of Alzheimer’s Disease
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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“Among the earliest responses of neurons to this accumulation of Aβ is an abnormal increase in excitability [3,4].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [3]
In the citing paper
“The hypoexcitability induced by tau pathology is different from the hyperactivity induced by APP or PSEN mutations88–90, which increases Aβ pathology in AD.”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [89]
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Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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