Wnt signaling in amygdala-dependent learning and memory

• Type of Material: Article
• Authors: Kimberly A. Maguschak, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2011-09-14
• Publisher: Society for Neuroscience
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 by the Society for Neuroscience
• Final Published Version (URL): http://dx.doi.org/10.1523%2FJNEUROSCI.3248-11.2011
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0270-6474
• Volume: 31
• Issue: 37
• Start Page: 13057
• End Page: 13067
• Grant/Funding Information: Support for this work was provided by the NIH (DA019624, P30 NS055077); the Burroughs Wellcome Fund; the National Science Foundation (NSF) (GRFP DGE-0234618); the Center for Behavioral Neuroscience, a Science and Technology Center of the NSF, under Agreement #IBN-9876754; National Primate Research Center Base Grant #RR-00165; and the Animal Resource Program at NIH. We thank Dennis C. Choi, PhD, for his invaluable assistance with these studies.
• Research Categories: Biology, Neuroscience

Abstract

In addition to its role in cellular development and proliferation, there are emerging in vitro data implicating the Wnt/β-catenin pathway in synaptic plasticity. Yet in vivo studies have not examined if Wnt activity is required for learning and memory. In the amygdala during fear memory formation, we found that many Wnt-signaling genes were dynamically regulated, with an immediate decrease, followed by an eventual normalization during memory consolidation. This rapid decrease in Wnt mRNA was confirmed with individual quantitative PCR and in situ hybridization. We then manipulated Wnt signaling with a specific peptide antagonist (Dkk-1) or agonist (Wnt1) injected stereotaxically into the adult amygdala during fear learning. We found that neither manipulation had an effect on locomotion, anxiety, fear acquisition or fear expression. However, both Wnt modulators prevented long-term fear memory consolidation without affecting short-term memory. Dkk-1 and Wnt infusions had destabilizing, but opposite, effects on the requisite β-catenin/cadherin dynamic interactions that occur during consolidation. These data suggest that dynamic modulation of Wnt/β-catenin signaling during consolidation is critical for the structural basis of long-term memory formation.