Dopaminergic neuromodulation in the motor cortex and its role for motor learning

• Applicant: Professor Dr. Andreas R. Luft
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2006 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 23937886

Learning of a complex novel movement is mediated by neuroplasticity mechanisms that are thought to resemble those that enable recovery of motor function after brain injury. Understanding these mechanisms is therefore of critical basic science and clinical relevance. Our preliminary work shows that motor learning depends on protein synthesis in motor cortex. Specifically, genes of dopaminergic signaling pathways are expressed in motor cortex during learning but not during motor activity: D2 receptor, regulator of g-protein signaling (RGS) 2 and 9. In several types of learning, the cortical dopaminergic system is induces cortical remodeling. We therefore hypothesize that cortical dopaminergic signaling is critically important for cortical plasticity mediating successful motor learning. We propose to investigate this hypothesis, first, by characterizing the time course and regional expression of target genes and proteins using quantitative PCR, Western blotting, and immunohistochemistry. Second, we will use the results of this characterization to specifically target the time phase of dopaminergic build-up with drugs (dopamine D1 and D2 agonists and antagonists) and RNA interference against RGS proteins that may disturb or improve motor learning efficacy. The latter experiments will prove or disprove a role of cortical dopaminergic neuromodulation for motor learning. If proven these findings may open new therapeutic alleys for promoting recovery of brain function using dopamine-modulating drugs ¿ initial evidence for a beneficial effect of levodopa for stroke recovery has been reported.

• DFG Programme: Research Grants