Beta-catenin is required for memory consolidation.
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.
Maguschak
Kimberly A
KA
Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Howard Hughes Medical Institute, Emory University, Atlanta, Georgia 30329, USA.
Ressler
Kerry J
KJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
D015820:Cadherins; D012333:RNA, Messenger; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride