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

Ajmal Zemmar, Oliver Weinmann, Yves Kellner, Xinzhu Yu, Raul Vicente, Miriam Gullo, Hansjörg Kasper, Karin Lussi, Zorica Ristic, Andreas R. Luft, Mengia Rioult-Pedotti, Yi Zuo, Marta Zagrebelsky, Martin E. Schwab

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)8685-8698
Number of pages14
JournalJournal of Neuroscience
Issue number26
StatePublished - 2014
Externally publishedYes


  • In vivo
  • LTP
  • Motor learning
  • Nogo-A
  • Synaptic plasticity
  • Two-photon

ASJC Scopus subject areas

  • Neuroscience(all)


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