期刊
NEUROBIOLOGY OF DISEASE
卷 154, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2021.105345
关键词
Dentate gyrus; Intrinsic excitability; Perforant pathway; Synaptic plasticity; Hippocampus; Glial cells; Neuroinflammation; Alzheimer' s disease
资金
- University of Bordeaux [201506890031]
- China Scholarship Council (CSC) [201506890031]
The study found that female APP/PS1 mice displayed early deficits in hippocampus-dependent memory tasks and heightened intrinsic excitability of DG granule cells as early as 3 months of age, which may be attributed to impaired synaptic plasticity induced by HFS.
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 A? 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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