Brain‐derived neurotrophic factor Val66Met polymorphism, human memory, and synaptic neuroplasticity

Abstract

Some people have much better memory than others, and there is compelling evidence that a considerable proportion of this variation in memory ability is genetically inherited. A form of synaptic plasticity known as long-term potentiation (LTP) is the principal candidate mechanism underlying memory formation in neural circuits, and it might be expected, therefore, that a genetic influence on the degree of LTP might in turn influence memory abilities. Of the genetic variations thought to significantly influence mnemonic ability in humans, the most likely to have its effect via LTP is a single nucleotide polymorphism affecting brain-derived neurotrophic factor [BDNF (Val66Met)]. However, although it is likely that BDNF influences memory via a modulation of acute plasticity (i.e., LTP), BDNF also has considerable influence on structural development of neural systems. Thus, the influence of BDNF (Val66Met) on mnemonic performance via influences of brain structure as well as function must also be considered. In this brief review, we will describe the phenomenon of LTP and its study in non-human animals. We will discuss the relatively recent attempts to translate this work to studies in humans. We will describe how this has enabled investigation of the effect of the BDNF polymorphism on LTP, on brain structure, and on memory performance.

A single exercise bout and locomotor learning after stroke: physiological, behavioural, and computational outcomes

“…One of those factors can be genetic variation. Such a genetic variation is the presence of a single-nucleotide polymorphism of the BDNF Val66Met gene, which may detrimentally influence the capacity of learning (Lamb et al 2015). In our previous work we found that post stroke subjects who are BDNF Val66Met carriers (MET) require more time to learn split-belt treadmill walking in a single session (i.e.…”

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian Learning mechanisms in the cerebral cortex

“…The BDNF Val66Met polymorphism is understood to impact the efficacy of NMDARdependent plasticity (Chen et al, 2004;Egan et al, 2003;Lamb et al, 2015), which is central to both the generation of the MMN Schmidt et al, would thus be reasonable to predict a comparable genetic group difference across both paradigms. However, genetic differences were only apparent in the modulation of backward connections for the MMN paradigm, with no significant genetic differences observed in the LTP generative network.…”

“…Approximately 25-50% of the population carry the rs6265 single nucleotide polymorphism (SNP) (4-16% homozygous) which substitutes valine to methionine at codon 66 (known as Val66Met) (Goldberg & Weinberger, 2004;Shimizu, Hashimoto, & Iyo, 2004). The Met allele of the SNP is associated with reduced secretion of BDNF, and thus has previously been implicated in the efficacy of NMDAR-dependent neuroplasticity and memory performance (Chen et al, 2004;Egan et al, 2003;Hariri et al, 2003;Lamb et al, 2015). Previous studies conducted in our lab using the LTP paradigm have demonstrated reduced potentiation of the N1b component of the VEP in BDNF Met carriers (Thompson et al, in prep).…”

Cognitive, Experiential and Genetic Contribution to Depressive Symptoms in Male and Female Students with a History of Concussion

“…Brain derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the brain, associated with synaptic plasticity and necessary in the mature brain to maintain dendritic density and structural integrity of neurons (Hofer et al, 1990;Wetmore et al, 1990;Ghosh et al, 1994;Murer et al, 2001;Lamb et al, 2014). The BDNF Val 66 Met polymorphism (rs6265), where adenosine (A) is substituted for guanine (G) at codon 66 leading to the valine (Val) being substituted by methionine (Met), is associated with less BDNF secretion and differences in brain function and structure (Pezawas et al, 2004;Lamb et al, 2014).…”

“…Brain derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the brain, associated with synaptic plasticity and necessary in the mature brain to maintain dendritic density and structural integrity of neurons (Hofer et al, 1990;Wetmore et al, 1990;Ghosh et al, 1994;Murer et al, 2001;Lamb et al, 2014). The BDNF Val 66 Met polymorphism (rs6265), where adenosine (A) is substituted for guanine (G) at codon 66 leading to the valine (Val) being substituted by methionine (Met), is associated with less BDNF secretion and differences in brain function and structure (Pezawas et al, 2004;Lamb et al, 2014). It has been shown that Met allele carriers have a reduced cortical thickness in the frontal lobe and ACC compared to Val allele carriers, and that the difference is more drastic in those diagnosed with MDD (Legge et al, 2015) The presence of a Met allele is associated with an increased risk for developing depression, although this finding is inconsistent (Egan et al, 2003;Verhagen et al, 2010).…”