Format

Send to

Choose Destination
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

1
Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
2
Department of Brain and Cognitive Sciences Massachusetts Institute of Technology, The Picower Institute for Learning and Memory, Cambridge, United States.
3
Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
4
Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States.
5
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, United States.
6
Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, United States.
7
Department of Psychology, University of Vermont, Burlington, United States.
8
Broad Institute of MIT and Harvard, Cambridge, United States.
#
Contributed equally

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.

KEYWORDS:

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

PMID:
28001126
PMCID:
PMC5293492
DOI:
10.7554/eLife.22467
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center