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Cited by 17Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Impaired plasticity of intrinsic excitability in the dentate gyrus alters spike transfer in a mouse model of Alzheimer's disease

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Jiang, Nan, Cupolillo, Dario, Grosjean, Noelle, Muller, Emeline, Deforges, Séverine, Mulle, Christophe, Amédée, Thierry·2021·Neurobiology of Disease
DOI 10.1016/j.nbd.2021.105345
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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline related to deficits in synaptic transmission and plasticity. We report in APP/PS1 mice, a double transgenic mouse model of AD, that females displayed an early burden of Aβ plaques load in the stratum moleculare of the dentate gyrus (DG) together with prominent neuroinflammatory activation of astrocytes and microglia. Robust deficits in hippocampus-dependent memory tasks were observed in APP/PS1 female mice as early as 3 months of age. We then studied the functional properties of the lateral perforant path (LPP) to DG granule cells. Remarkably DG granule cells displayed higher intrinsic excitability in APP/PS1 female mice. We showed that the long term potentiation of population spike amplitude induced by high frequency stimulation (HFS) at LPP-DG granule cells synapse is impaired in APP/PS1 female mice. HFS induced plasticity of intrinsic excitability in DG granule cells without inducing noticeable modification of synaptic strength. Furthermore, the enhanced intrinsic excitability was potentiated to a greater extent in APP/PS1 as compared to control mice following HFS. Our study shows that changes in the intrinsic excitability of DG granule cells in AD contribute to the dysfunctional transfer of information from the entorhinal cortex to the hippocampus.

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  • Synaptic plasticity in the dentate gyrus is strongly affected in mouse models of AD.

    “Synaptic plasticity in the DG is strongly affected in mouse models of AD25,26.”

    From PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures (2026) · cites this paper as [25]

    The Results (§3.4; page unavailable) found no significant long-term change in synaptic strength after stimulation in either genotype. The Discussion (§4.3; page unavailable) attributes the altered dentate-gyrus spike transfer in APP/PS1 mice chiefly to plasticity of intrinsic excitability, a nonsynaptic form of plasticity, rather than strongly affected synaptic plasticity. (LLM, conf=0.87)

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References 78 · Cited by 17

Research works printed but not linked: 25

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Authors
Jiang, N., Cupolillo, D., Grosjean, N., Muller, E., Deforges, S., Mulle, C., & Amédée, T.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Amédée, Thierry
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2021-07
Volume
154
Pages
105345
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2021.105345
OpenAlex
W3139346173
Cited by
17
References
78
Citations by year
2025: 3 · 2024: 8 · 2023: 5 · 2021: 1
FWCI
2.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • China Scholarship Council (201506890031)
  • Université de Bordeaux (201506890031)
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 › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
Alzheimer's disease, APP/PS1 mice, dentate gyrus granule cells, intrinsic excitability, lateral perforant path, long-term potentiation, high-frequency stimulation, amyloid plaques, neuroinflammation, astrocytes, microglia, sex differences, hippocampal-dependent memory, entorhinal cortex, synaptic plasticity
MeSH terms
Action Potentials, Alzheimer Disease, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Amyloid beta-Protein Precursor, Dentate Gyrus, Mice, Presenilin-1

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