title: Wnt signaling in amygdala-dependent learning and memory.
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 whether 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Maguschak
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051155:Wnt1 Protein / Q000008:administration & dosage / Q000096:biosynthesis* / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin