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The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner

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  • Bisrat T. Woldemichael

    (Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich
    Present address: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA)

  • Ali Jawaid

    (Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich)

  • Eloïse A. Kremer

    (Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich)

  • Niharika Gaur

    (Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich)

  • Jacek Krol

    (Friedrich Miescher Institute for Biomedical Research)

  • Antonin Marchais

    (Institute of Agricultural Sciences, Swiss Federal Institute of Technology)

  • Isabelle M. Mansuy

    (Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich)

Abstract

Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signalling regulator, protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster and its selective regulation during memory formation. Inhibiting nuclear PP1 in the mouse brain, or training on an object recognition task similarly increases miR-183/96/182 expression in the hippocampus. Mimicking this increase by miR-183/96/182 overexpression enhances object memory, while knocking-down endogenous miR-183/96/182 impairs it. This effect involves the modulation of several plasticity-related genes, with HDAC9 identified as an important functional target. Further, PP1 controls miR-183/96/182 in a transcription-independent manner through the processing of their precursors. These findings provide novel evidence for a role of miRNAs in memory formation and suggest the implication of PP1 in miRNAs processing in the adult brain.

Suggested Citation

  • Bisrat T. Woldemichael & Ali Jawaid & Eloïse A. Kremer & Niharika Gaur & Jacek Krol & Antonin Marchais & Isabelle M. Mansuy, 2016. "The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12594
    DOI: 10.1038/ncomms12594
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