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

Bisrat T. Woldemichael, Ali Jawaid, Eloïse A. Kremer, Niharika Gaur, Jacek Krol, Antonin Marchais and Isabelle M. Mansuy ()
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Bisrat T. Woldemichael: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich
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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12594

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