Wilm’s tumor 1 promotes memory flexibility

Chiara Mariottini (), Leonardo Munari, Ellen Gunzel, Joseph M. Seco, Nikos Tzavaras, Jens Hansen, Sarah A. Stern, Virginia Gao, Hossein Aleyasin, Ali Sharma, Evren U. Azeloglu, Georgia E. Hodes, Scott J. Russo, Vicki Huff, Marc R. Birtwistle, Robert D. Blitzer, Cristina M. Alberini () and Ravi Iyengar ()
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Chiara Mariottini: Icahn School of Medicine at Mount Sinai
Leonardo Munari: Icahn School of Medicine at Mount Sinai
Ellen Gunzel: Icahn School of Medicine at Mount Sinai
Joseph M. Seco: Icahn School of Medicine at Mount Sinai
Nikos Tzavaras: Icahn School of Medicine at Mount Sinai
Jens Hansen: Icahn School of Medicine at Mount Sinai
Sarah A. Stern: Icahn School of Medicine at Mount Sinai
Virginia Gao: Icahn School of Medicine at Mount Sinai
Hossein Aleyasin: Icahn School of Medicine at Mount Sinai
Ali Sharma: Icahn School of Medicine at Mount Sinai
Evren U. Azeloglu: Icahn School of Medicine at Mount Sinai
Georgia E. Hodes: Icahn School of Medicine at Mount Sinai
Scott J. Russo: Icahn School of Medicine at Mount Sinai
Vicki Huff: University of Texas
Marc R. Birtwistle: Icahn School of Medicine at Mount Sinai
Robert D. Blitzer: Icahn School of Medicine at Mount Sinai
Cristina M. Alberini: Icahn School of Medicine at Mount Sinai
Ravi Iyengar: Icahn School of Medicine at Mount Sinai

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11781-x

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