Department of Psychiatry, University of Puerto Rico School of Medicine, San Juan, PR 00936.
Science. 2010 Jun 4;328(5983):1288-90. doi: 10.1126/science.1186909.
The extinction of conditioned fear memories requires plasticity in the infralimbic medial prefrontal cortex (IL mPFC), but little is known about the molecular mechanisms involved. Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity in multiple brain areas. In rats subjected to auditory fear conditioning, BDNF infused into the IL mPFC reduced conditioned fear for up to 48 hours, even in the absence of extinction training, which suggests that BDNF substituted for extinction. Similar to extinction, BDNF-induced reduction in fear required N-methyl-D-aspartate receptors and did not erase the original fear memory. Rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC, and augmenting BDNF in this pathway prevented extinction failure. Hence, boosting BDNF activity in hippocampal-infralimbic circuits may ameliorate disorders of learned fear.
条件性恐惧记忆的消除需要下边缘脑区的内侧前额叶皮质（IL mPFC）的可塑性，但关于涉及的分子机制知之甚少。脑源性神经营养因子（BDNF）是多个脑区突触可塑性的关键介质。在接受听觉恐惧条件反射的大鼠中，将 BDNF 注入 IL mPFC 可使条件性恐惧减少长达 48 小时，即使没有进行消退训练，这表明 BDNF 可以替代消退。与消退类似，BDNF 诱导的恐惧减少需要 N-甲基-D-天冬氨酸受体，并且不会抹去原始的恐惧记忆。未能学习消退的大鼠显示出海马传入到 IL mPFC 的 BDNF 减少，而增强该途径中的 BDNF 可防止消退失败。因此，增强海马-下边缘回路中的 BDNF 活性可能会改善习得性恐惧障碍。
