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MicroRNA-128 governs neuronal excitability and motor behavior in mice

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  • Chan Lek Tan, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, United States
  • Joshua L. Plotkin, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
  • Morten Trillingsgaard Venø, Denmark
  • Melanie von Schimmelmann, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
  • Philip Feinberg, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, United States
  • Silas Mann, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
  • Annie Handler, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA, United States
  • Jørgen Kjems
  • D. James Surmeier, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
  • Dónal O’Carroll, European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy and Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, United States
  • Paul Greengard, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, United States
  • Anne Schaefer, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal-regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson's-like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.
Original languageEnglish
JournalScience
Volume342
Issue6163
Pages (from-to)1254-1258
Number of pages5
ISSN0036-8075
DOIs
Publication statusPublished - 6 Dec 2013

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