Intense training overcomes effects of the val66met BDNF polymorphism on short-term plasticity

Stephanie A Mchughen,Steven C Cramer,Kristin Pearson-Fuhrhop,Vivian K Ngo

doi:10.1007/s00221-011-2791-z

Abstract

The val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene impacts activity-dependent secretion of BDNF and modifies short-term cortical plasticity. The current study examined whether sustained training overcomes polymorphism effects on short-term plasticity and also examined polymorphism effects on long-term plasticity. Twenty-four subjects completed a 12-day protocol of daily training on a marble navigation task that required intense use of the first dorsal interosseus (FDI) muscle. In parallel, transcranial magnetic stimulation (TMS) mapping was used to assess serial measures of short-term cortical motor map plasticity, plus long-term cortical motor map plasticity, of the cortical FDI map. On Day 1, subjects with the polymorphism did not show significant short-term cortical motor map plasticity over 30min of FDI activity, but subjects without the polymorphism did. After 5days of intense training, a genotype-based difference in short-term cortical motor map plasticity was no longer found, as both groups showed short-term plasticity across the 30min of FDI activity. Also, across 12days of training, map area decreased significantly, in a manner that did not vary in relation to genotype. Training of sufficient intensity and duration overcomes effects that the val(66)met polymorphism has on short-term cortical motor map plasticity. The polymorphism-related differences seen with short-term plasticity are not found with long-term cortical motor map plasticity.

Highlights

IntroductionAn opportunity to study changes in the human brainderived neurotrophic factor (BDNF) system arises in the context of a single nucleotide polymorphism at codon 66 of the BDNF gene (val66met), which is common (Shimizu et al 2004) and associated with reduced activity-dependent BDNF release (Egan et al 2003)
The current study examined whether sustained training overcomes polymorphism effects on short-term plasticity and examined polymorphism effects on long-term plasticity
A secondary aim of this study was to understand the effects of the val66met brainderived neurotrophic factor (BDNF) polymorphism on longerterm forms of plasticity, i.e., over time periods measured in days rather than minutes, a consideration that arises given that short-term and long-term forms of cortical plasticity arise on the basis of different neuronal mechanisms (Karni et al 1995; Costa et al 2004; Floyer-Lea and Matthews 2005)

Summary

Introduction

An opportunity to study changes in the human BDNF system arises in the context of a single nucleotide polymorphism at codon 66 of the BDNF gene (val66met), which is common (Shimizu et al 2004) and associated with reduced activity-dependent BDNF release (Egan et al 2003) Presence of this val66met polymorphism has been associated with numerous effects on the brain, including differences in cortical morphology (Pezawas et al 2004), hippocampal function and synaptic plasticity (Egan et al 2003), and episodic memory (Egan et al 2003; Ho et al 2006). An observation important to this investigation is that this polymorphism has been associated with reduced short-term plasticity in motor cortex (Kleim et al 2006; Exp Brain Res (2011) 213:415–422 These findings raise the question as to whether experience, such as with sustained training, can overcome these polymorphism effects on short-term plasticity. An improved understanding of polymorphism effects on long-term forms of brain plasticity is of considerable clinical relevance

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