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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cognition / physiology*
  • Endocytosis / genetics
  • Endocytosis / physiology
  • Female
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Hippocampus / ultrastructure
  • Immunoblotting
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / genetics
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Immunoelectron
  • N-Methylaspartate / pharmacology
  • Neurons / metabolism
  • Neurons / physiology
  • Protein Binding
  • Receptors, AMPA / metabolism
  • Synapses / metabolism
  • Synapses / physiology
  • Synaptosomes / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • CTNNB1 protein, mouse
  • Cadherins
  • Receptors, AMPA
  • beta Catenin
  • N-Methylaspartate