Abstract

Brain-derived neurotrophic factor (BDNF) has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language). A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT) to determine implicit motor learning and a recently established associative vocabulary learning task (AVL) for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22) and met carriers (val/met: n = 15 and met/met: n = 1). There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.

Highlights

  • Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophic factors in the adult brain, associated with development, synaptic plasticity and learning [1,2,3]

  • A single nucleotide polymorphism (SNP) at codon 66 leads to an exchange of valin to methionin resulting in three genotypes with varying distribution worldwide [6]

  • Previous studies addressing the effects of BDNF on either motor learning or non-invasive brain stimulation were based on comparatively small group sizes (total group size: median = 24 persons; met-carrier group size: median 7.5 [8,15,16,17,18,19,20,21,22])

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Summary

Introduction

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophic factors in the adult brain, associated with development, synaptic plasticity and learning [1,2,3]. While the polymorphism does not alter the mature BDNF structure, it impairs its trafficking resulting in: 1) decreased variant BDNF distribution into neuronal dendrites; 2) decreased targeting to secretory granules and 3) subsequent impairment of regulated, activity-dependent secretion [2,5]. These defects have been associated with neuroanatomical and behavioural differences between young healthy subjects, e.g., hippocampal volume [11] and function (i.e. episodic memory [2,12]) is decreased in metcarriers.

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