Dendritic Structural Degeneration Is Functionally Linked to Cellular Hyperexcitability in a Mouse Model of Alzheimer’s Disease
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Dendritic structure critically determines the electrical properties of neurons and, thereby, defines the fundamental process of input-to-output conversion. The diversity of dendritic architectures enables neurons to fulfill their specialized circuit functions during cognitive processes. It is known that this dendritic integrity is impaired in patients with Alzheimer's disease and in relevant mouse models. It is unknown, however, whether this structural degeneration translates into aberrant neuronal function. Here we use in vivo whole-cell patch-clamp recordings, high-resolution STED imaging, and computational modeling of CA1 pyramidal neurons in a mouse model of Alzheimer's disease to show that structural degeneration and neuronal hyperexcitability are crucially linked. Our results demonstrate that a structure-dependent amplification of synaptic input to action potential output conversion might constitute a novel cellular pathomechanism underlying network dysfunction with potential relevance for other neurodegenerative diseases with abnormal changes of dendritic morphology.
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AD is also associated with progressive neurite degeneration.
“Since AD is also associated with progressive neurite degeneration (51), we examined neurite outgrowth in spheroids.”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [51]
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- Authors
- Šišková, Z., Justus, D., Kaneko, H., Friedrichs, D., Henneberg, N., Beutel, T., Pitsch, J., Schoch, S., Becker, A., von der Kammer, H., & Remy, S.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- University of Bonn (DE)
- Corresponding author
- Remy, Stefan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 84
- Issue
- 5
- Pages
- 1023-1033
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2062605351
- Cited by
- 320
- References
- 54
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 39 · 2023: 23 · 2022: 34 · 2021: 44 · 2020: 32 · 2019: 21 · 2018: 18 · 2017: 19 · 2016: 23 · 2015: 13 · 2014: 2
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- neuronal hyperexcitability, Alzheimer's disease, CA1 pyramidal neurons, dendritic morphology, network dysfunction, mouse models of Alzheimer's disease, computational modeling
- MeSH terms
- Action Potentials, Alzheimer Disease, Animals, Computer Simulation, Dendrites, Disease Models, Animal, Electric Stimulation, Female, Hippocampus, Humans, Lysine, Male, Mice, Transgenic, Models, Neurological, Mutation, Nerve Degeneration, Neurons, Amyloid beta-Protein Precursor, Mice, Presenilin-1, In Vitro Techniques
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