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Impairment of hippocampal gamma (γ)‐frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP)
Author(s) -
Driver Joanne E.,
Racca Claudia,
Cunningham Mark O.,
Towers Stephen K.,
Davies Ceri H.,
Whittington Miles A.,
LeBeau Fiona E. N.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05705.x
Subject(s) - hippocampal formation , amyloid precursor protein , wild type , medicine , alzheimer's disease , endocrinology , hippocampus , amyloid (mycology) , neuroscience , chemistry , biology , pathology , biochemistry , disease , gene , mutant
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 n m kainate was significantly ( P < 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 µV 2 ) compared to slices from wild‐type animals (area power, 18 256 ± 7880 µV 2 ). 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 µV 2 ). 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.