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Wilm's tumor 1 promotes memory flexibility.

Authors :
Mariottini C
Munari L
Gunzel E
Seco JM
Tzavaras N
Hansen J
Stern SA
Gao V
Aleyasin H
Sharma A
Azeloglu EU
Hodes GE
Russo SJ
Huff V
Birtwistle MR
Blitzer RD
Alberini CM
Iyengar R
Source :
Nature communications [Nat Commun] 2019 Aug 21; Vol. 10 (1), pp. 3756. Date of Electronic Publication: 2019 Aug 21.
Publication Year :
2019

Abstract

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however, the underlying mechanisms that enable memory flexibility are still poorly understood. Here, we identify transcriptional repressor Wilm's Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 is activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhances CA1 neuronal excitability, LTP and long-term memory whereas its overexpression weakens memory retention. Moreover, forebrain WT1-deficient mice show deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experiences.

Details

Language :
English
ISSN :
2041-1723
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
31434897
Full Text :
https://doi.org/10.1038/s41467-019-11781-x