The role of brain-derived neurotrophic factor in cortical motor learning.

摘要

The molecular mechanisms that mediate learning have not yet been fully identified. The neurotrophic factor brain-derived neurotrophic factor (BDNF) exhibits properties that make it a candidate molecule for investigations of learning-related plasticity. The experiments described in this dissertation tested the hypothesis that BDNF exerts a role in normal cortical learning and map plasticity in the adult animal. The experimental paradigm used cortical motor learning, in which normal adult rats were trained in a skilled forelimb reaching task. The first set of experiments examined the expression of BDNF and its high-affinity receptor, TrkB, as a function of motor skill learning, to assess whether learning modulates the transcriptional regulation of these molecules. The next set of experiments utilized two methods of attenuating BDNF signaling in the forepaw motor cortex: lentivirus encoding small interfering RNAs (siRNA) directed against BDNF mRNA, and lentivirus encoding a TrkB receptor body which binds BDNF, rendering it unavailable for normal signaling. The combined results lead to the conclusion that, although BDNF expression is modulated by motor learning, reducing the availability of BDNF protein in the motor cortex by 22% using siRNA, or binding extracellular BDNF to an unknown extent using a TrkB receptor body, does not affect motor learning or motor map organization.