Brain-derived neurotrophic factor (BDNF) is critical for establishing activity-related neural plasticity. There is increasing interest in the mechanisms of active avoidance and its extinction, but little is known about the role of BDNF in these processes. Using the platform-mediated avoidance task combined with local infusions of an antibody against BDNF, we show that blocking BDNF in either prelimbic (PL) or infralimbic (IL) medial prefrontal cortex during extinction training impairs subsequent recall of extinction of avoidance, differing from extinction of conditioned freezing. By combining retrograde tracers with BDNF immunohistochemistry, we show that extinction of avoidance increases BDNF expression in ventral hippocampal (vHPC) neurons, but not amygdala neurons, projecting to PL and IL. Using the CRISPR/Cas9 system, we further show that reducing BDNF production in vHPC neurons impairs recall of avoidance extinction. Thus, the vHPC may mediate behavioral flexibility in avoidance by driving extinction-related plasticity via BDNFergic projections to both PL and IL. These findings add to the growing body of knowledge implicating the hippocampal-prefrontal pathway in anxiety-related disorders and extinction-based therapies.

中文翻译：

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内侧前额皮质和腹侧海马 BDNF 的改变会损害回避的消退。

脑源性神经营养因子（BDNF）对于建立与活动相关的神经可塑性至关重要。人们对主动回避及其消退的机制越来越感兴趣，但人们对 BDNF 在这些过程中的作用知之甚少。使用平台介导的回避任务结合局部注射 BDNF 抗体，我们发现在消退训练期间阻断前边缘（PL）或下边缘（IL）内侧前额叶皮层的 BDNF 会损害随后对回避消退的回忆，这与消退不同条件冷冻。通过将逆行示踪剂与 BDNF 免疫组织化学相结合，我们发现回避的消失会增加腹侧海马 (vHPC) 神经元的 BDNF 表达，但不会增加杏仁核神经元的 BDNF 表达，并投射到 PL 和 IL。使用 CRISPR/Cas9 系统，我们进一步表明，减少 vHPC 神经元中 BDNF 的产生会损害对避免灭绝的回忆。因此，vHPC 可能通过 BDNFergic 对 PL 和 IL 的预测来驱动与灭绝相关的可塑性，从而介导回避行为的灵活性。这些发现丰富了关于海马-前额叶通路在焦虑相关疾病和基于灭绝的治疗中的作用的知识体系。