title: Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo.
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.
authors.affiliation: Departments of Cellular and Physiological Sciences.
authors.forename: Fergil
authors.initials: F
authors.lastname: Mills
authors.affiliation: Medicine, and.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Bartlett
authors.affiliation: Psychiatry, Brain Research Center, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and.
authors.forename: Lasse
authors.initials: L
authors.lastname: Dissing-Olesen
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109, Warsaw, Poland.
authors.forename: Marta B
authors.identifier: http://orcid.org/0000-0002-1593-0361
authors.initials: MB
authors.lastname: Wisniewska
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuznicki
authors.affiliation: Psychiatry, Brain Research Center, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Macvicar
authors.affiliation: Medicine, and.
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Departments of Cellular and Physiological Sciences, shernaz.bamji@ubc.ca.
authors.forename: Shernaz X
authors.initials: SX
authors.lastname: Bamji
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D015151:Immunoblotting; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; D018091:Receptors, AMPA; D051176:beta Catenin; D016202:N-Methylaspartate