文章基本信息

标题：Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo
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作者：Fergil Mills ; Thomas E. Bartlett ; Lasse Dissing-Olesen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：23
页码：8631-8636
DOI：10.1073/pnas.1404670111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.