Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear
Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear
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DOI：
10.1073/pnas.0909359107
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发表时间：
2010-02-09
影响因子：
11.1
通讯作者：
Ressler, Kerry J.
中科院分区：
文献类型：
--
作者：
Choi, Dennis C.;Maguschak, Kimberly A.;Ressler, Kerry J.
在内侧前额叶皮层中，前边缘区正在成为恐惧行为的主要调节器，但其机制仍不清楚。使用选择性新皮质基因敲除小鼠，病毒介导的前边缘皮质特异性基因缺失，和药理学救援与TrkB激动剂，我们研究了一个主要的候选机制，BDNF，在条件性恐惧的作用。我们发现一贯强大的赤字巩固线索的恐惧，但没有影响收购，表达未习得的恐惧，感觉运动功能和空间学习。在BDNF敲除小鼠中学习恐惧的这种缺陷通过全身施用TrkB受体激动剂7，8-二羟基黄酮来挽救。这些数据表明，前边缘脑源性神经营养因子是巩固习得的恐惧记忆的关键，但它不是天生的恐惧或消除恐惧所必需的。此外，使用位点特异性的，可诱导的BDNF缺失显示了一个强大的机制，可能会进一步加深我们对恐惧相关疾病的病理生理学的理解。
In the medial prefrontal cortex, the prelimbic area is emerging as a major modulator of fear behavior, but the mechanisms remain unclear. Using a selective neocortical knockout mouse, virally mediated prelimbic cortical-specific gene deletion, and pharmacological rescue with a TrkB agonist, we examined the role of a primary candidate mechanism, BDNF, in conditioned fear. We found consistently robust deficits in consolidation of cued fear but no effects on acquisition, expression of unlearned fear, sensorimotor function, and spatial learning. This deficit in learned fear in the BDNF knockout mice was rescued with systemic administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data indicate that prelimbic BDNF is critical for consolidation of learned fear memories, but it is not required for innate fear or extinction of fear. Moreover, use of site-specific, inducible BDNF deletions shows a powerful mechanism that may further our understanding of the pathophysiology of fear-related disorders.