title: 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.
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Mathew
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Antonis
authors.initials: A
authors.lastname: Tatarakis
authors.affiliation: Department of Brain and Cognitive Sciences Massachusetts Institute of Technology, The Picower Institute for Learning and Memory, Cambridge, United States.
authors.forename: Andrii
authors.initials: A
authors.lastname: Rudenko
authors.affiliation: Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Johnson-Venkatesh
authors.affiliation: Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States.|Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, United States.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, United States.
authors.forename: Yawei J
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Murphy
authors.affiliation: Department of Psychology, University of Vermont, Burlington, United States.
authors.forename: Travis P
authors.initials: TP
authors.lastname: Todd
authors.affiliation: Department of Psychology, University of Vermont, Burlington, United States.
authors.forename: Scott T
authors.identifier: 0000-0001-8051-7541
authors.initials: ST
authors.lastname: Schepers
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Nertila
authors.initials: N
authors.lastname: Siuti
authors.affiliation: Department of Brain and Cognitive Sciences Massachusetts Institute of Technology, The Picower Institute for Learning and Memory, Cambridge, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Martorell
authors.affiliation: Department of Psychology, University of Vermont, Burlington, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Falls
authors.affiliation: Department of Psychology, University of Vermont, Burlington, United States.
authors.forename: Sayamwong E
authors.initials: SE
authors.lastname: Hammack
authors.affiliation: Division of Genetics, Howard Hughes Medical Institute, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, United States.|Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, United States.|Broad Institute of MIT and Harvard, Cambridge, United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.affiliation: Department of Brain and Cognitive Sciences Massachusetts Institute of Technology, The Picower Institute for Learning and Memory, Cambridge, United States.|Broad Institute of MIT and Harvard, Cambridge, United States.
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
authors.affiliation: Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Hisashi
authors.identifier: 0000-0001-7198-2062
authors.initials: H
authors.lastname: Umemori
authors.affiliation: Department of Psychology, University of Vermont, Burlington, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bouton
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Danesh
authors.identifier: 0000-0003-0321-6221
authors.initials: D
authors.lastname: Moazed
mesh_terms: D000818:Animals; D005239:Fear; D025461:Feedback, Physiological; D006624:Hippocampus / Q000502:physiology*; D008568:Memory; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: C577878:MIRN153 microRNA, mouse; D035683:MicroRNAs; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate
keywords: cell biology; hippocampus; learning; memory; miRNA; mouse; negative feed back loop; rat; synaptic plasticity