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

作者：Mathew Rebeca S; Tatarakis Antonis; Rudenko Andrii; Johnson Venkatesh Erin M; Yang Yawei J; Murphy Elisabeth A; Todd Travis P; Schepers Scott T; Siuti Nertila; Martorell Anthony J; Falls William A; Hammack Sayamwong E; Walsh Christopher A; Tsai Li Huei; Umemori Hisashi; Bouton Mark E; Moazed Danesh^*

来源：eLife, 2016, 5: e22467.

DOI：10.7554/eLife.22467

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.

• 出版日期2016-12-21
• 单位MIT