title: MicroRNA-137 Controls AMPA-Receptor-Mediated Transmission and mGluR-Dependent LTD.
abstract: Mutations affecting the levels of microRNA miR-137 are associated with intellectual disability and schizophrenia. However, the pathophysiological role of miR-137 remains poorly understood. Here, we describe a highly conserved miR-137-binding site within the mRNA encoding the GluA1 subunit of AMPA-type glutamate receptors (AMPARs) and confirm that GluA1 is a direct target of miR-137. Postsynaptic downregulation of miR-137 at the CA3-CA1 hippocampal synapse selectively enhances AMPAR-mediated synaptic transmission and converts silent synapses to active synapses. Conversely, miR-137 overexpression selectively reduces AMPAR-mediated synaptic transmission and silences active synapses. In addition, we find that miR-137 is transiently upregulated in response to metabotropic glutamate receptor 5 (mGluR5), but not mGluR1 activation. Consequently, acute interference with miR-137 function impedes mGluR-LTD expression. Our findings suggest that miR-137 is a key factor in the control of synaptic efficacy and mGluR-dependent synaptic plasticity, supporting the notion that glutamatergic dysfunction contributes to the pathogenesis of miR-137-linked cognitive impairments.
authors.affiliation: Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Nikkie F M
authors.initials: NF
authors.lastname: Olde Loohuis
authors.affiliation: Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Wei
authors.initials: W
authors.lastname: Ba
authors.affiliation: Institute of Physiological Chemistry, Biochemical-Pharmacological Center Marburg, Philipps University Marburg, 35032 Marburg, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Stoerchel
authors.affiliation: Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Aron
authors.initials: A
authors.lastname: Kos
authors.affiliation: Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jager
authors.affiliation: Institute of Physiological Chemistry, Biochemical-Pharmacological Center Marburg, Philipps University Marburg, 35032 Marburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schratt
authors.affiliation: Department of Molecular Animal Physiology, Radboud University Nijmegen, 6525 HP Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Gerard J M
authors.initials: GJ
authors.lastname: Martens
authors.affiliation: Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.affiliation: Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands. Electronic address: n.nadif@donders.ru.nl.
authors.forename: Nael
authors.initials: N
authors.lastname: Nadif Kasri
authors.affiliation: Department of Neuroinformatics, Radboud University Nijmegen, 6525 HP Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ Nijmegen, the Netherlands. Electronic address: a.aschrafi@donders.ru.nl.
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
mesh_terms: D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000096:biosynthesis* / Q000235:genetics; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: C000595679:MIRN137 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1