title: The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory.
abstract: MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory.
  
  
  
  Despite the abundant expression of the brain-specific microRNA miR-9-5p/3p in both proliferating and postmitotic neurons, most functional studies have focused on their role in neuronal development. Here, we examined the role of miR-9-5p/3p in adult brain and found that miR-9-3p, but not miR-9-5p, has a critical role in hippocampal synaptic plasticity and memory. Moreover, we identified in vivo binding targets of miR-9-3p that are involved in the regulation of long-term potentiation. Our study provides the very first evidence for the critical role of miR-9-3p in synaptic plasticity and memory in the adult mouse.
authors.affiliation: Department of Brain and Cognitive Sciences.
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Sim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Chae-Seok
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Jae-Ick
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Center for RNA Research, Institute for Basic Science, and.
authors.forename: Daekwan
authors.identifier: 0000-0002-8628-6120
authors.initials: D
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Heejung
authors.initials: H
authors.lastname: Chun
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Nam-Kyung
authors.identifier: 0000-0002-7432-7394
authors.initials: NK
authors.lastname: Yu
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Brain and Cognitive Sciences.
authors.forename: SukJae Joshua
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Hyoung-Gon
authors.identifier: 0000-0002-7730-6986
authors.initials: HG
authors.lastname: Ko
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Jun-Hyeok
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: TaeHyun
authors.identifier: 0000-0003-3871-5776
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Brain and Cognitive Sciences.
authors.forename: Eun-Hae
authors.initials: EH
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 06974, Republic of Korea.
authors.forename: Myeong Seong
authors.initials: MS
authors.lastname: Bak
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Center for RNA Research, Institute for Basic Science, and.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, Sangju 37224, Republic of Korea, and.
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Center for RNA Research, Institute for Basic Science, and Bioinformatics Institute, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Daehyun
authors.initials: D
authors.lastname: Baek
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 06974, Republic of Korea yongseok@cau.ac.kr kaang@snu.ac.kr.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Brain and Cognitive Sciences, Department of Biological Sciences, College of Natural Sciences, yongseok@cau.ac.kr kaang@snu.ac.kr.
authors.forename: Bong-Kiun
authors.identifier: 0000-0001-7593-9707
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D000074288:Discs Large Homolog 1 Protein; D016189:Dystrophin / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C527276:CXCR4 protein, human; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D016189:Dystrophin; C541874:MIRN92 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D019718:Receptors, CXCR4; D016704:Synapsins; C085339:apo-dystrophin 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases
keywords: hippocampus; long-term potentiation; memory; microRNA