Department of Psychology, University of Montreal, Montréal, Quebec, Canada.
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Verdun, Quebec, Canada.
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.
人们可以使用依赖于不同记忆系统的多种策略在新环境中导航。一系列研究已经将海马体依赖的“空间”导航和由尾状核介导的基于习惯的“反应”学习区分开来。脑源性神经营养因子 (BDNF) 基因的 val66met 多态性导致大脑中包括海马体在内的 BDNF 分泌减少。在这里，我们旨在研究 BDNF val66met 多态性对健康老年人虚拟导航行为和大脑活动的作用。本研究共纳入 139 名健康老年人（平均年龄=65.8±4.4 岁）。采集血样并进行 BDNF val66met 基因分型。参与者被分为两种基因型组：val 纯合子和 met 携带者。参与者在虚拟双解导航任务中接受测试，他们可以使用海马体依赖的空间策略或尾状核依赖的反应策略来解决任务。然后，参与者的一部分（n=66）在 3T 功能磁共振成像（fMRI）扫描仪中进行扫描，同时进行另一项双解导航任务。BDNF val/val 个体和 met 携带者在学习表现上没有差异。然而，这两个 BDNF 组在学习策略上有所不同。BDNF val/val 个体更多地依赖地标来记住目标位置（即，增加灵活的空间学习），而 met 携带者更多地依赖序列和模式来记住目标位置（即，增加不灵活的反应学习）。此外，BDNF val/val 个体在执行导航任务时，海马体的 fMRI 活性高于 BDNF met 携带者。这是第一项在老年人中表明 BDNF met 携带者使用与 val/val 个体不同的替代学习策略的研究，并确定了这两组之间这种行为差异的大脑激活差异。
