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β-catenin is required for memory consolidation

Abstract

β-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined β-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in β-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of β-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of β-catenin. Genetically, the role of β-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding β-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, β-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for β-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.

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Figure 1: β-catenin expression in the adult mouse brain.
Figure 2: β-catenin gene expression in the amygdala is increased after fear conditioning.
Figure 3: Phosphorylation states of β-catenin and GSK-3β are altered after fear conditioning.
Figure 4: LiCl decreases GSK-3β-mediated β-catenin phosphorylation in the amygdala and enhances learning.
Figure 5: Region-specific deletion of β-catenin in the adult brain.
Figure 6: Amygdala-specific β-catenin deletions do not affect baseline anxiety or activity measures.
Figure 7: Amygdala-specific Ctnnb1 deletion prevents the consolidation, but not expression, of conditioned fear.

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Acknowledgements

This work was supported by the National Institutes of Health (MH069884, DA019624 and AG025688), the National Science Foundation (GRFP DGE-0234618), the Center for Behavioral Neuroscience (NSF agreement IBN-987675), the Burroughs Wellcome Fund and an NIH/National Center for Research Resources base grant (P51RR000165) to the Yerkes National Primate Research Center.

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K.A.M. initiated the project, conducted the experiments and data analysis and wrote the draft versions of the manuscript. K.J.R. supervised the project, assisted with data analysis and experimental planning, and contributed to draft and revised versions of the manuscript.

Corresponding author

Correspondence to Kerry J Ressler.

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Maguschak, K., Ressler, K. β-catenin is required for memory consolidation. Nat Neurosci 11, 1319–1326 (2008). https://doi.org/10.1038/nn.2198

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