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, Ravi Iyengar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number3756
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Mariottini, C., Munari, L., Gunzel, E., Seco, J. M., Tzavaras, N., Hansen, J., Stern, S. A., Gao, V., Aleyasin, H., Sharma, A., Azeloglu, E. U., Hodes, G. E., Russo, S. J., Huff, V., Birtwistle, M. R., Blitzer, R. D., Alberini, C. M., & Iyengar, R. (2019). Wilm’s tumor 1 promotes memory flexibility. Nature communications, 10(1), [3756]. https://doi.org/10.1038/s41467-019-11781-x