期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 23, 页码 8631-8636出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1404670111
关键词
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资金
- Canadian Institutes of Health Research [MOP-81158, MOP-38090]
- American Alzheimer's Association [NIRG-07-58917]
- Alzheimer Society of Canada
- Polish Ministry of Science and Higher Education [4245/B/P01/2010/38]
The cadherin/beta-catenin adhesion complex is a key mediator of the bidirectional changes in synapse strength which are believed to underlie complex learning and memory. In the present study, we demonstrate that stabilization of beta-catenin in the hippocampus of adult mice results in significant impairments in cognitive flexibility and spatial reversal learning, including impaired extinction during the reversal phase of the Morris water maze and deficits in a delayed nonmatch to place T-maze task. In accordance with these deficits, beta-catenin stabilization was found to abolish long-term depression by stabilizing cadherin at the synaptic membrane and impairing AMPA receptor endocytosis, while leaving basal synaptic transmission and long-term potentiation unaffected. These results demonstrate that the beta-catenin/cadherin adhesion complex plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have deleterious effects on cognitive function.
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