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Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo.

Authors
  • Zemmar, Ajmal1
  • Weinmann, Oliver2
  • Kellner, Yves3
  • Yu, Xinzhu4
  • Vicente, Raul5
  • Gullo, Miriam2
  • Kasper, Hansjörg6
  • Lussi, Karin6
  • Ristic, Zorica2
  • Luft, Andreas R7
  • Rioult-Pedotti, Mengia7
  • Zuo, Yi4
  • Zagrebelsky, Marta3
  • Schwab, Martin E2
  • 1 Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, [email protected] , (Switzerland)
  • 2 Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland. , (Switzerland)
  • 3 Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany. , (Germany)
  • 4 Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California 95064.
  • 5 Department of Neurophysiology, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany, and. , (Germany)
  • 6 Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland. , (Switzerland)
  • 7 Clinical Neurorehabilitation, Department of Neurology, University and University Hospital, Zurich, 8008 Zurich, Switzerland. , (Switzerland)
Type
Published Article
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Publication Date
Jun 25, 2014
Volume
34
Issue
26
Pages
8685–8698
Identifiers
DOI: 10.1523/JNEUROSCI.3817-13.2014
PMID: 24966370
Source
Medline
Keywords
License
Unknown

Abstract

The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex.

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