miR-181a Participates in Contextual Fear Memory Formation Via Activating mTOR Signaling Pathway

Cereb Cortex. 2018 Sep 1;28(9):3309-3321. doi: 10.1093/cercor/bhx201.

Abstract

Long-term memory formation has been proven to require gene expression and new protein synthesis. MicroRNAs (miRNAs), as an endogenous small non-coding RNAs, inhibit the expression of their mRNA targets, through which involve in new memory formation. In this study, elevated miR-181a levels were found to be responsible for hippocampal contextual fear memory consolidation. Using a luciferase reporter assay, we indicated that miR-181a targets 2 upstream molecules of mTOR pathway, namely, PRKAA1 and REDD1. Upregulated miR-181a can downregulate the PRKAA1 and REDD1 protein levels and promote mTOR activity to facilitate hippocampal fear memory consolidation. These results indicate that miR-181a is involved in hippocampal contextual fear memory by activating the mTOR signaling pathway. This work provides a novel evidence for the role of miRNAs in memory formation and demonstrates the implication of mTOR signaling pathway in miRNA processing in the adult brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fear / physiology
  • Gene Expression Regulation / genetics*
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Signal Transduction / genetics*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • MicroRNAs
  • mirn181 microRNA, mouse
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases