Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

Fergil Mills; Thomas E. Bartlett; Lasse Dissing-OlesenMarta B. WisniewskaJacek KuznickiBrian A. MacvicarYu Tian WangShernaz X. Bamji

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Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

机译：Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

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The cadherin/β-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 β-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, β-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 β-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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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第23期|8631-8636|共6页
作者
Fergil Mills; Thomas E. Bartlett; Lasse Dissing-OlesenMarta B. WisniewskaJacek KuznickiBrian A. MacvicarYu Tian WangShernaz X. Bamji;
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作者单位

Departments of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;

Departments of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;

Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109, Warsaw, PolandDepartments of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
cadherin/β-catenin; bidirectional; present;

Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

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