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Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8631-6. doi: 10.1073/pnas.1404670111. Epub 2014 May 27.

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

Author information

1
Departments of Cellular and Physiological Sciences.
2
Medicine, and.
3
Psychiatry, Brain Research Center, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and.
4
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109, Warsaw, Poland.
5
Departments of Cellular and Physiological Sciences, shernaz.bamji@ubc.ca.

Abstract

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.

PMID:
24912177
PMCID:
PMC4060709
DOI:
10.1073/pnas.1404670111
[Indexed for MEDLINE]
Free PMC Article

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