Canonical Wnt signaling is necessary for object recognition memory consolidation. J Neurosci 2013 Jul 31;33(31):12619-26
Date
08/02/2013Pubmed ID
23904598Pubmed Central ID
PMC6618550DOI
10.1523/JNEUROSCI.0659-13.2013Scopus ID
2-s2.0-84880849552 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
Wnt signaling has emerged as a potent regulator of hippocampal synaptic function, although no evidence yet supports a critical role for Wnt signaling in hippocampal memory. Here, we sought to determine whether canonical β-catenin-dependent Wnt signaling is necessary for hippocampal memory consolidation. Immediately after training in a hippocampal-dependent object recognition task, mice received a dorsal hippocampal (DH) infusion of vehicle or the canonical Wnt antagonist Dickkopf-1 (Dkk-1; 50, 100, or 200 ng/hemisphere). Twenty-four hours later, mice receiving vehicle remembered the familiar object explored during training. However, mice receiving Dkk-1 exhibited no memory for the training object, indicating that object recognition memory consolidation is dependent on canonical Wnt signaling. To determine how Dkk-1 affects canonical Wnt signaling, mice were infused with vehicle or 50 ng/hemisphere Dkk-1 and protein levels of Wnt-related proteins (Dkk-1, GSK3β, β-catenin, TCF1, LEF1, Cyclin D1, c-myc, Wnt7a, Wnt1, and PSD95) were measured in the dorsal hippocampus 5 min or 4 h later. Dkk-1 produced a rapid increase in Dkk-1 protein levels and a decrease in phosphorylated GSK3β levels, followed by a decrease in β-catenin, TCF1, LEF1, Cyclin D1, c-myc, Wnt7a, and PSD95 protein levels 4 h later. These data suggest that alterations in Wnt/GSK3β/β-catenin signaling may underlie the memory impairments induced by Dkk-1. In a subsequent experiment, object training alone rapidly increased DH GSK3β phosphorylation and levels of β-catenin and Cyclin D1. These data suggest that canonical Wnt signaling is regulated by object learning and is necessary for hippocampal memory consolidation.
Author List
Fortress AM, Schram SL, Tuscher JJ, Frick KMAuthors
Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - MilwaukeeJennifer J. Tuscher PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCyclin D1
Disks Large Homolog 4 Protein
Dose-Response Relationship, Drug
Exploratory Behavior
Functional Laterality
Gene Expression Regulation
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Guanylate Kinases
Hippocampus
Intercellular Signaling Peptides and Proteins
Male
Membrane Proteins
Memory Disorders
Mice
Mice, Inbred C57BL
Phosphorylation
Signal Transduction
Statistics, Nonparametric
Wnt Proteins
beta Catenin
