Brain-derived neurotrophic factor plays a critical role in contextual fear conditioning
Brain-derived neurotrophic factor plays a critical role in contextual fear conditioning
复制标题
DOI：
10.1523/jneurosci.1948-04.2004
复制
发表时间：
2004-09-08
影响因子：
5.3
通讯作者：
Thompson, RF
中科院分区：
文献类型：
--
作者：
Liu, IYC;Lyons, WE;Thompson, RF
在这项研究中，脑源性神经营养因子（BDNF）杂合敲除进行了测试的恐惧条件反射，其野生型同窝仔作为对照。结果表明，BDNF+/-小鼠在上下文学习中受损，而音调学习保持完整。由于BDNF参与突触传递，而情境学习是海马依赖性的，我们假设这种缺陷是由于海马中BDNF调节的突触可塑性异常。接下来通过将重组BDNF蛋白注入海马结构进行“功能获得”实验，以研究是否可以挽救这种缺陷。将BDNF蛋白输注到海马中似乎部分恢复了BDNF+/-小鼠的情境恐惧学习。总之，本研究表明，BDNF在恐惧条件反射中起着关键作用。BDNF基因的一个拷贝的丢失导致BDNF+/-的情境恐惧学习受损。这种缺陷可以通过将BDNF蛋白注入海马体来部分挽救。在情境条件刺激通路中与海马体相互作用的其他脑区，例如杏仁核，也可能需要正常的BDNF表达水平来完全挽救这种损伤。
In this study, brain-derived neurotrophic factor (BDNF) heterozygous knock-outs were tested on fear conditioning, and their wild-type littermates were used as controls. Results showed that BDNF+/- mice are impaired in contextual learning, whereas tone learning remains intact. Because BDNF is involved in synaptic transmission and contextual learning is hippocampal dependent, we hypothesized that this deficit is attributable to abnormal BDNF-modulated synaptic plasticity in the hippocampus. A "gain-of-function" experiment was performed next by infusing recombinant BDNF protein into the hippocampal formation to investigate whether this deficit can be rescued. Infusion of BDNF protein into the hippocampus appeared to partially restore contextual fear learning of BDNF+/- mice. In conclusion, the present study suggests that BDNF plays a critical role in fear conditioning. Loss of one copy of the BDNF gene leads to impairment of contextual fear learning in BDNF+/-. This deficit can be partially rescued by infusing BDNF protein into the hippocampus. Other brain regions interacting with the hippocampus in the context conditioned stimulus pathway, for example, the amygdala, may also require normal BDNF expression levels to fully rescue this impairment.