Hippocampal-Prefrontal BDNF and Memory for Fear Extinction
Hippocampal-Prefrontal BDNF and Memory for Fear Extinction
复制标题
DOI：
10.1038/npp.2014.64
复制
发表时间：
2014-08-01
影响因子：
7.6
通讯作者：
Quirk, Gregory J.
中科院分区：
文献类型：
--
作者：
Rosas-Vidal, Luis E.;Do-Monte, Fabricio H.;Quirk, Gregory J.
将脑源性神经营养因子（BDNF）注入下边缘（IL）前额皮质能够诱导灭绝。然而，关于介导BDNF对灭绝的影响的电路或灭绝需要IL中的BDNF的程度知之甚少。使用局部药物输注BDNF蛋白或BDNF抗体，我们发现IL中的BDNF，而不是前边缘（PL）前额叶皮层，是恐惧消退的必要和充分条件。此外，我们报告白细胞介素中的脑源性神经营养因子可以诱导较旧的恐惧记忆（14天）以及最近的恐惧记忆（1天）的消失。使用免疫细胞化学，我们表明，BDNF增加腹侧海马（vHPC），但不是IL或PL，以下灭绝训练。最后，我们观察到，注入BDNF到vHPC增加了IL的放电率，但不是恐惧条件大鼠PL神经元。这些发现表明，vHPC中BDNF的抑制诱导的增加增强了IL靶点的兴奋性，从而支持消退记忆。
Infusing brain-derived neurotrophic factor (BDNF) into the infralimbic (IL) prefrontal cortex is capable of inducing extinction. Little is known, however, about the circuits mediating BDNF effects on extinction or the extent to which extinction requires BDNF in IL. Using local pharmacological infusion of BDNF protein, or an antibody against BDNF, we found that BDNF in the IL, but not prelimbic (PL) prefrontal cortex, is both necessary and sufficient for fear extinction. Furthermore, we report that BDNF in IL can induce extinction of older fear memories (14 days) as well as recent fear memories (1 day). Using immunocytochemistry, we show that BDNF is increased in the ventral hippocampus (vHPC), but not IL or PL, following extinction training. Finally, we observed that infusing BDNF into the vHPC increased the firing rate of IL, but not PL neurons in fear conditioned rats. These findings indicate that an extinction-induced increase in BDNF within the vHPC enhances excitability in IL targets, thereby supporting extinction memories.