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Impairment of hippocampal gamma (γ)-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP)

Lookup NU author(s): Dr Claudia RaccaORCiD, Professor Mark Cunningham, Professor Miles Whittington, Dr Fiona LeBeau


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Alzheimer's disease is associated with a dramatic decline in cognitive performance including hippocampal-dependent memory. We have investigated one feature of hippocampal activity related to memory, the γ (30-80 Hz)-frequency rhythm. Hippocampal slices from mice overexpressing the human amyloid precursor protein (APP)SWE mutation (TAS10) were compared at 8 and 16 months of age with wild-type littermates. In slices obtained from TAS10 mice aged 8 months the γ-frequency activity evoked with bath application of 200 nm kainate was significantly (P < 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 μV2) compared to slices from wild-type animals (area power, 18 256 ± 7880 μV2). At 16 months of age there was no longer a significant difference (P > 0.05; n = 11 slices from five animals) between slices from TAS10 and wild-type control mice as the wild-type mice now exhibited a marked age-dependent reduction in γ-frequency activity (TAS10 area power, 5751 ± 1573 μV 2; wild-type area power = 5379 ± 1454 μV2). Although no dense-core plaques were evident at 8 months there was detectable amyloid labelling in the TAS10 mice which might account for the deficits in γ activity observed at this age. Dense plaques were clearly evident in the TAS10, but not wild-type, mice at 16 months of age but no further reductions in γ-frequency activity were seen in the TAS10 mice. These data suggest that deficits in network function in Alzheimer's disease occur early and are not directly correlated to amyloid load. © The Authors (2007).

Publication metadata

Author(s): Driver JE, Racca C, Cunningham MO, Towers SK, Davies CH, Whittington MA, Le Beau FEN

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2007

Volume: 26

Issue: 5

Pages: 1280-1288

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1460-9568.2007.05705.x

PubMed id: 17767505


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