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

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.

SUBMITTER: Mathew RS

PROVIDER: S-EPMC5293492 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Mathew Rebecca S RS Tatarakis Antonis A Rudenko Andrii A Johnson-Venkatesh Erin M EM Yang Yawei J YJ Murphy Elisabeth A EA Todd Travis P TP Schepers Scott T ST Siuti Nertila N Martorell Anthony J AJ Falls William A WA Hammack Sayamwong E SE Walsh Christopher A CA Tsai Li-Huei LH Umemori Hisashi H Bouton Mark E ME Moazed Danesh D

eLife 20161221

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 ...[more]

PMID: 28001126

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

Publications

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

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