title: Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo.
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.
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland, zemmar@hifo.uzh.ch.
authors: Ajmal
authors: http://orcid.org/0000-0003-1463-3338
authors: A
authors: Zemmar
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland.
authors: Oliver
authors: O
authors: Weinmann
authors: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
authors: Yves
authors: Y
authors: Kellner
authors: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California 95064.
authors: Xinzhu
authors: X
authors: Yu
authors: Department of Neurophysiology, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany, and.
authors: Raul
authors: R
authors: Vicente
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland.
authors: Miriam
authors: M
authors: Gullo
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
authors: Hansjörg
authors: H
authors: Kasper
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
authors: Karin
authors: K
authors: Lussi
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland.
authors: Zorica
authors: Z
authors: Ristic
authors: Clinical Neurorehabilitation, Department of Neurology, University and University Hospital, Zurich, 8008 Zurich, Switzerland.
authors: Andreas R
authors: AR
authors: Luft
authors: Clinical Neurorehabilitation, Department of Neurology, University and University Hospital, Zurich, 8008 Zurich, Switzerland.
authors: Mengia
authors: M
authors: Rioult-Pedotti
authors: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California 95064.
authors: Yi
authors: Y
authors: Zuo
authors: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
authors: Marta
authors: M
authors: Zagrebelsky
authors: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland, Department of Health Sciences and Technology, ETH Zurich, 8057 Zurich, Switzerland.
authors: Martin E
authors: ME
authors: Schwab
mesh_terms: D000818:Animals; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000502:physiology*; D009048:Motor Skills / Q000502:physiology*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat
keywords: LTP; Nogo-A; in vivo; motor learning; synaptic plasticity; two-photon