Cited by 321Neuroscience and Neuropharmacology ResearchAlzheimer's disease research and treatmentsNeural dynamics and brain function

Dendritic Structural Degeneration Is Functionally Linked to Cellular Hyperexcitability in a Mouse Model of Alzheimer’s Disease

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Šišková, Zuzana, Justus, Daniel, Kaneko, Hiroshi, Friedrichs, Detlef, Henneberg, Niklas, Beutel, Tatjana, Pitsch, Julika, Schoch, Susanne +3 more·2014·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2014.10.024

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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
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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