. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci. 2006 Jun;9(6):735-7. PubMed.

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  1. This paper adds to the growing literature in live human subjects that demonstrates a deficit in activity-dependent plasticity caused by the val66met polymorphism in the BDNF gene. The original in vitro data show that the val66met polymorphism does not affect constitutive secretion but reduces stimulation-dependent BDNF secretion. This paper is consistent with that data in that there was no difference between val/val, val/met, and met/met genotypes with respect to baseline measures including performance of fine motor tasks, but there was a significant effect of even one met allele on motor map changes with training. Whereas short periods of motor training increased the amplitude of motor-evoked potentials and motor map volume in val/val subjects, even one met allele was sufficient to abolish this plasticity. It should be noted that, because the val66met polymorphism is in the prodomain of the BDNF protein, this paper supports the model that it is proBDNF and not mature BDNF that is mobilized at the synapse in response to activity.