A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory
Author(s)Mathew, Rebecca S; Tatarakis, Antonis; Johnson-Venkatesh, Erin M; Murphy, Elisabeth A; Todd, Travis P; Schepers, Scott T; Siuti, Nertila; Falls, William A; Hammack, Sayamwong E; Walsh, Christopher A; Umemori, Hisashi; Bouton, Mark E; Moazed, Danesh; Rudenko, Andrii; Martorell, Anthony; Tsai, Li-Huei; Yang, Yawei; ... Show more Show less
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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.
DepartmentInstitute for Medical Engineering and Science; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
eLife Sciences Publications, Ltd.
Mathew, Rebecca S et al. “A microRNA Negative Feedback Loop Downregulates Vesicle Transport and Inhibits Fear Memory.” eLife 5 (2016): n. pag. © 2016 eLife Sciences Publications Ltd.
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