期刊
HIPPOCAMPUS
卷 24, 期 8, 页码 963-978出版社
WILEY-BLACKWELL
DOI: 10.1002/hipo.22283
关键词
spatial tuning; hippocampal place cell; cognitive decline; CA1; amyloid
资金
- NIH/OD [DP2 OD001734]
- NIH/NIA [T32 AG000183]
- Robert A. and Rene E. Belfer Family Foundation
- Bill and Melinda Gates Foundation
- Gates Millennium Scholarship
- BCM Alzheimer's Disease and Memory Disorders Center
- George and Cynthia Mitchell Foundation
Impaired spatial memory characterizes many mouse models for Alzheimer's disease, but we understand little about how this trait arises. Here, we use a transgenic model of amyloidosis to examine the relationship between behavioral performance in tests of spatial navigation and the function of hippocampal place cells. We find that amyloid precursor protein (APP) mice require considerably more training than controls to reach the same level of performance in a water maze task, and recall the trained location less well 24 h later. At a single cell level, place fields from control mice become more stable and spatially restricted with repeated exposure to a new environment, while those in APP mice improve less over time, ultimately producing a spatial code of lower resolution, accuracy, and reliability than controls. The limited refinement of place fields in APP mice likely contributes to their delayed water maze acquisition, and provides evidence for circuit dysfunction underlying cognitive impairment. (C) 2014 Wiley Periodicals, Inc.
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