Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo
Open accessAbstract
Significance: Complex learning and memory are believed to require the weakening or elimination of synapses in the brain, a process mediated by adhesion molecules, which maintain synapse strength and stability. In the present study, we examine in vivo the effects of stabilization of β-catenin, an intracellular protein that is a component of the cadherin adhesion complex. We find that stabilization of β-catenin in the brain prevents normal activity-dependent downscaling of synapse strength, resulting in a striking impairment in cognitive flexibility. These results demonstrate that β-catenin plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have detrimental effects on cognitive function.
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LTD is required for optimal reversal learning.
“Indeed, LTD is required for optimal reversal learning: administration of a ionotropic glutamate receptor NMDA subunit 2B (GluN2B) selective antagonist or blockade of GluA-R internalization prevents LTD in the hippocampus, and produces a disruption of spatial reversal learning in the Morris water maze (Dong et al 2013, Duffy et al 2008, Mills et al 2014).”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Mills et al 2014
Administration of a GluN2B selective antagonist or blockade of GluA-R internalization prevents hippocampal LTD and disrupts spatial reversal learning in the Morris water maze.
“Indeed, LTD is required for optimal reversal learning: administration of a ionotropic glutamate receptor NMDA subunit 2B (GluN2B) selective antagonist or blockade of GluA-R internalization prevents LTD in the hippocampus, and produces a disruption of spatial reversal learning in the Morris water maze (Dong et al 2013, Duffy et al 2008, Mills et al 2014).”
From Prefrontal cortex executive processes affected by stress in health and disease (2018) · cites this paper as Mills et al 2014
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Prefrontal cortex executive processes affected by stress in health and disease
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- Authors
- Mills, F., Bartlett, T. E., Dissing-Olesen, L., Wisniewska, M. B., Kuznicki, J., Macvicar, B. A., Wang, Y. T., & Bamji, S. X.
- Affiliations
- Departments of aCellular and Physiological Sciences,
- Medicine, and
- Psychiatry, Brain Research Center, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; and
- International Institute of Molecular and Cell Biology (PL)
- Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109, Warsaw, Poland
- University of British Columbia (CA)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-05-27
- Volume
- 111
- Issue
- 23
- Pages
- 8631-8636
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4060709
- OpenAlex
- W2008206245
- Cited by
- 82
- References
- 42
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 10 · 2021: 11 · 2020: 5 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 8
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Alzheimer Society
- Canadian Institutes of Health Research (MOP-38090, MOP-81158)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- β-catenin stabilization, long-term depression, cognitive flexibility, spatial reversal learning, extinction learning, hippocampus, AMPA receptor endocytosis, synaptic adhesion, learning and memory, long-term potentiation, synaptic plasticity
- MeSH terms
- Animals, Cognition, Endocytosis, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Protein Binding, Synapses, Synaptosomes, Immunoblotting, Cadherins, N-Methylaspartate, Microscopy, Immunoelectron, Receptors, AMPA, Mice, Knockout, Maze Learning, Long-Term Synaptic Depression, beta Catenin, Mice
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