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

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

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Title: A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory
Author: Mathew, Rebecca 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

Note: Order does not necessarily reflect citation order of authors.

Citation: Mathew, R. S., A. Tatarakis, A. Rudenko, E. M. Johnson-Venkatesh, Y. J. Yang, E. A. Murphy, T. P. Todd, et al. 2016. “A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.” eLife 5 (1): e22467. doi:10.7554/eLife.22467. http://dx.doi.org/10.7554/eLife.22467.
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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. DOI: http://dx.doi.org/10.7554/eLife.22467.001
Published Version: doi:10.7554/eLife.22467
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293492/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:31731816
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