Microrna-137 controls ampa-receptor-mediated transmission and mglur-dependent ltd
| Autor: | Aron Kos, Peter H. Stoerchel, Amanda Jager, Nikkie F.M. Olde Loohuis, Armaz Aschrafi, Gerard J.M. Martens, Hans van Bokhoven, Gerhard Schratt, Wei Ba, Nael Nadif Kasri |
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| Rok vydání: | 2015 |
| Předmět: |
Neuroinformatics
Receptor Metabotropic Glutamate 5 Neurophysiology Other Research Donders Center for Medical Neuroscience [Radboudumc 0] AMPA receptor Biology Receptors Metabotropic Glutamate General Biochemistry Genetics and Molecular Biology Intellectual Disability Metaplasticity Animals Humans RNA Messenger Receptors AMPA lcsh:QH301-705.5 GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Binding Sites Neuronal Plasticity Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] Metabotropic glutamate receptor 5 musculoskeletal neural and ocular physiology Molecular Animal Physiology Rats MicroRNAs Synaptic fatigue lcsh:Biology (General) Gene Expression Regulation nervous system Metabotropic glutamate receptor Synaptic plasticity Silent synapse Immunology Mutation Synapses Schizophrenia Metabotropic glutamate receptor 1 Neuroscience |
| Zdroj: | Cell Reports, 11, 1876-1884 Cell Reports, 11, 12, pp. 1876-84 Cell Reports, 11, 12, pp. 1876-1884 Cell Reports, 11, 1876-84 Cell Reports, Vol 11, Iss 12, Pp 1876-1884 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryMutations 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. |
| Databáze: | OpenAIRE |
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