Beta-catenin is required for memory consolidation

Nat Neurosci. 2008 Nov;11(11):1319-26. doi: 10.1038/nn.2198. Epub 2008 Sep 28.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Cadherins / metabolism
  • Conditioning, Psychological / physiology
  • Exploratory Behavior / physiology
  • Fear
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Green Fluorescent Proteins / biosynthesis
  • Lithium Chloride / pharmacology
  • Male
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Time Factors
  • beta Catenin / genetics*
  • beta Catenin / metabolism*

Substances

  • Cadherins
  • RNA, Messenger
  • beta Catenin
  • Green Fluorescent Proteins
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Lithium Chloride