Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo
| Autor: | Yves Kellner, Karin Lussi, Raul Vicente, Ajmal Zemmar, Andreas R. Luft, Oliver Weinmann, Marta Zagrebelsky, Yi Zuo, Miriam Gullo, Mengia Rioult-Pedotti, Martin E. Schwab, Hansjörg Kasper, Zorica Ristic, Xinzhu Yu |
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| Přispěvatelé: | University of Zurich, Zemmar, A |
| Rok vydání: | 2014 |
| Předmět: |
Male
Dendritic spine Nogo Proteins Long-Term Potentiation 610 Medicine & health Biology Basic Behavioral and Social Science Medical and Health Sciences Rats Sprague-Dawley Synaptic augmentation Behavioral and Social Science mental disorders medicine Animals Learning Motor skill two-photon synaptic plasticity Neurology & Neurosurgery General Neuroscience Psychology and Cognitive Sciences Neurosciences Motor Cortex 2800 General Neuroscience Long-term potentiation Articles Rats 10040 Clinic for Neurology in vivo Mental Health Synaptic fatigue medicine.anatomical_structure Motor Skills Neurological Synaptic plasticity Synapses Sprague-Dawley LTP Nogo-A Motor learning motor learning Neuroscience Myelin Proteins psychological phenomena and processes Motor cortex |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 34, iss 26 Journal of Neuroscience |
| DOI: | 10.1523/JNEUROSCI.3817-13.2014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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