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

Nat Commun. 2016 Aug 25:7:12594. doi: 10.1038/ncomms12594.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exploratory Behavior
  • Hippocampus / metabolism
  • Learning
  • Memory, Long-Term*
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Multigene Family*
  • Neuronal Plasticity / genetics
  • Neurons / metabolism
  • Protein Phosphatase 1 / antagonists & inhibitors
  • Protein Phosphatase 1 / metabolism*
  • RNA Processing, Post-Transcriptional
  • Task Performance and Analysis
  • Up-Regulation / genetics


  • MicroRNAs
  • Protein Phosphatase 1