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Wilm's tumor 1 promotes memory flexibility.
- 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.
- Subjects :
- Animals
Behavior, Animal physiology
CA1 Region, Hippocampal metabolism
Fear physiology
Long-Term Potentiation physiology
Male
Memory Disorders pathology
Mice
Mice, Knockout
Neuronal Plasticity physiology
Neurons physiology
Rats
Rats, Sprague-Dawley
Repressor Proteins genetics
WT1 Proteins
Hippocampus physiology
Memory physiology
Repressor Proteins metabolism
Subjects
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