A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory
Name
Mathew-2016-A microRNA negative feedback loop.pdf
Size
36.86 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Mathew, Rebecca S
Tatarakis, Antonis
Johnson-Venkatesh, Erin M
Murphy, Elisabeth A
Todd, Travis P
Schepers, Scott T
Siuti, Nertila
Falls, William A
Hammack, Sayamwong E
Walsh, Christopher A
Date Issued
December 2016
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Mathew, Rebecca S et al. “A microRNA Negative Feedback Loop Downregulates Vesicle Transport and Inhibits Fear Memory.” eLife 5 (2016): n. pag. © 2016 eLife Sciences Publications Ltd.
Version
Final published version
Abstract
The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.
MIT Department
Institute for Medical Engineering and Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/eLife.22467
