Lonsdorf Tina B, Weike Almut I, Golkar Armita, Schalling Martin, Hamm Alfons O, Öhman Arne
Department of Clinical Neuroscience, Psychology Section, Stockholm Brain Institute, Karolinska Institutet.
Earnst-Moritz-Arndt University of Greifswald.
Behav Neurosci. 2010 Feb;124(1):9-15. doi: 10.1037/a0018261.
The brain-derived neurotrophic factor (BDNF) is critically involved in neuroplasticity, as well as the acquisition, consolidation, and retention of hippocampal- and amygdala-dependent learning. A common functional A-->G single nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is associated with abnormal intracellular trafficking and reduced activity-dependent BDNF release. We studied the effect of BDNFval66met in an aversive differential fear conditioning, and a delayed extinction paradigm in 57 healthy participants. Pictures of male faces were used as stimuli and fear learning was quantified by fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF met-carriers show a deficit in amygdala-dependent fear conditioning as indicated by an absence of FPS responses in the last acquisition block. This deficit was maintained in the first block of extinction. No genotype differences were found in conditioned SCR discrimination. These data provide evidence for the involvement of BDNF signaling in human amygdala-dependent learning. We suggest that the BDNF met-allele may have a protective effect for the development of affective pathologies that may be mediated via reduced synaptic plasticity induced by negative experience.
脑源性神经营养因子（BDNF）在神经可塑性以及海马体和杏仁核依赖性学习的获得、巩固和保持过程中起着关键作用。人类BDNF基因前结构域中常见的功能性A→G单核苷酸多态性（BDNFval66met）与细胞内运输异常以及活性依赖性BDNF释放减少有关。我们在57名健康参与者中研究了BDNFval66met在厌恶性差异恐惧条件反射和延迟消退范式中的作用。使用男性面部图片作为刺激物，通过恐惧增强惊吓反应（FPS）和皮肤电传导反应（SCR）对恐惧学习进行量化。有意识的BDNF met等位基因携带者在杏仁核依赖性恐惧条件反射中表现出缺陷，这在最后一个获得阶段表现为缺乏FPS反应。这种缺陷在消退的第一个阶段仍然存在。在条件性SCR辨别中未发现基因型差异。这些数据为BDNF信号传导参与人类杏仁核依赖性学习提供了证据。我们认为，BDNF met等位基因可能对情感病理学的发展具有保护作用，这可能是通过减少负面经历诱导的突触可塑性来介导的。
