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

eLife

Danesh Moazed¹  Travis P Todd²  Elisabeth A Murphy³  Mark E Bouton³  Andrii Rudenko⁴  Sayamwong E Hammack⁴  Antonis Tatarakis⁵  Rebecca S Mathew⁵  William A Falls⁵  Erin M Johnson-Venkatesh⁶  Li-Huei Tsai⁷  Nertila Siuti⁷  Anthony J Martorell⁷  Christopher A Walsh⁷  Yawei J Yang⁸  Hisashi Umemori⁸  Scott T Schepers⁸ 

[1] Broad Institute of MIT and Harvard, Cambridge, United States;Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, United States;Program in Biological and Biomedical Sciences, 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 Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States;Department of Neurology, FM Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, United States;Department of Psychology, University of Vermont, Burlington, United States;Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States;

关键词: learning;    memory;    synaptic plasticity;    miRNA;    hippocampus;    negative feed back loop;   

DOI  :  10.7554/eLife.22467

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown