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The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

Nature Neuroscience volume 14, pages 1115–1117 (2011)Cite this article

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Abstract

MicroRNAs are small non-coding RNAs that mediate post-transcriptional gene silencing. Fear-extinction learning in C57/Bl6J mice led to increased expression of the brain-specific microRNA miR-128b, which disrupted stability of several plasticity-related target genes and regulated formation of fear-extinction memory. Increased miR-128b activity may therefore facilitate the transition from retrieval of the original fear memory toward the formation of a new fear-extinction memory.

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Figure 1: Extinction training leads to increased mIR-128b expression and is necessary for the formation of fear-extinction memory.
Figure 2: mIR-128b functionally interacts with target genes, which decreases target gene expression.
Figure 3: Extinction training leads to decreased RCS levels, and knockdown of RCS in the ILPFC enhances fear-extinction memory.

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Acknowledgements

We thank P. Greengard and A. Nairn for their comments and the generous gift of RCS antibody, G. Quirk and C. Stevenson for suggestions, and R. Tweedale for editing the manuscript. This work was supported by a scholar award from the Michael Smith Foundation for Health Research (M.S.K.), a US National Institutes of Health EUREKA grant (R01 MH084095, Y.E.S.), and previous grants from the Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research and the National Institute on Drug Abuse (K99DA026503-01), and a current grant from the Australian Research Council (DP1096148, T.W.B.).

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  1. Quan Lin and Wei Wei: These authors contributed equally to this work.

Authors and Affiliations

  1. Intellectual Development and Disabilities Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA

    Quan Lin & Yi E Sun

  2. Psychiatric Epigenomics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia

    Wei Wei, Carlos M Coelho, Xiang Li, Danay Baker-Andresen, Kevin Dudley, Vikram S Ratnu, Zoran Boskovic & Timothy W Bredy

  3. Centre for Molecular Medicine and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada

    Michael S Kobor

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  1. Quan Lin
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Contributions

Q.L. conceived the project, prepared the lentiviral constructs, carried out the experiments and wrote the manuscript. W.W. prepared lentiviral constructs, carried out the luciferase assay and quantitative PCR experiments and wrote the manuscript. C.M.C. performed behavioral experiments. X.L. performed behavioral experiments and contributed to in vitro studies. D.B.-A. assisted with the molecular experiments. K.D. contributed to in vitro experiments. V.S.R. performed quantitative PCR studies. Z.B. performed the miR-128bOx behavioral experiments. M.S.K. contributed reagents and helped write the manuscript. Y.E.S. contributed reagents and helped design the experiments. T.W.B conceived the project, designed experiments and wrote the manuscript.

Corresponding author

Correspondence to Timothy W Bredy.

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The authors declare no competing financial interests.

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Supplementary Figures 1–13, Supplementary Table 1 and Supplementary Methods (PDF 1461 kb)

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Lin, Q., Wei, W., Coelho, C. et al. The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Nat Neurosci 14, 1115–1117 (2011). https://doi.org/10.1038/nn.2891

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