The BDNF val66met polymorphism is associated with decreased use of landmarks and decreased fMRI activity in the hippocampus during virtual navigation

Eur J Neurosci. 2021 Oct;54(7):6406-6421. doi: 10.1111/ejn.15431. Epub 2021 Sep 14.


People can navigate in a new environment using multiple strategies dependent on different memory systems. A series of studies have dissociated between hippocampus-dependent 'spatial' navigation and habit-based 'response' learning mediated by the caudate nucleus. The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene leads to decreased secretion of BDNF in the brain, including the hippocampus. Here, we aim to investigate the role of the BDNF val66met polymorphism on virtual navigation behaviour and brain activity in healthy older adults. A total of 139 healthy older adult participants (mean age = 65.8 ± 4.4 years) were tested in this study. Blood samples were collected, and BDNF val66met genotyping was performed. Participants were divided into two genotype groups: val homozygotes and met carriers. Participants were tested on virtual dual-solution navigation tasks in which they could use either a hippocampus-dependent spatial strategy or a caudate nucleus-dependent response strategy to solve the task. A subset of the participants (n = 66) were then scanned in a 3T functional magnetic resonance imaging (fMRI) scanner while engaging in another dual-solution navigation task. BDNF val/val individuals and met carriers did not differ in learning performance. However, the two BDNF groups differed in learning strategy. BDNF val/val individuals relied more on landmarks to remember target locations (i.e., increased use of flexible spatial learning), while met carriers relied more on sequences and patterns to remember target locations (i.e., increased use of inflexible response learning). Additionally, BDNF val/val individuals had more fMRI activity in the hippocampus compared with BDNF met carriers during performance on the navigation task. This is the first study to show in older adults that BDNF met carriers use alternate learning strategies from val/val individuals and to identify differential brain activation of this behavioural difference between the two groups.

Keywords: BDNF; ageing; caudate nucleus; hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain-Derived Neurotrophic Factor* / genetics
  • Genotype
  • Hippocampus* / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Spatial Navigation*


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human

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