Journal
CEREBRAL CORTEX
Volume 28, Issue 9, Pages 3309-3321Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhx201
Keywords
hippocampus; memory; miR-181a; mTOR
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Funding
- National Natural Science Foundation of China [31571321, 31171428, 31571100, 91432306, 31401219]
- Shandong Province Natural Science Foundation [ZR2014CM036, ZR2014CQ023]
- National Key Research and Development Program of China [2016YFE0129200]
- Fundamental Research Funds of Shandong University [2015JC036]
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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.
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