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Elife. 2016 Dec 21;5. pii: e22467. doi: 10.7554/eLife.22467.

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.

Author information

Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
Department of Brain and Cognitive Sciences Massachusetts Institute of Technology, The Picower Institute for Learning and Memory, Cambridge, United States.
Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States.
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, United States.
Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, United States.
Department of Psychology, University of Vermont, Burlington, United States.
Broad Institute of MIT and Harvard, Cambridge, United States.
Contributed equally


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.


cell biology; hippocampus; learning; memory; miRNA; mouse; negative feed back loop; rat; synaptic plasticity

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