Rosas-Vidal Luis E, Do-Monte Fabricio H, Sotres-Bayon Francisco, Quirk Gregory J
Departments of Psychiatry and Anatomy and Neurobiology, University of Puerto Rico, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.
Neuropsychopharmacology. 2014 Aug;39(9):2161-9. doi: 10.1038/npp.2014.64. Epub 2014 Mar 14.
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.
将脑源性神经营养因子（BDNF）注入边缘下（IL）前额叶皮层能够诱导消退。然而，关于介导BDNF对消退作用的神经回路，或者IL中消退对BDNF的依赖程度，我们所知甚少。通过局部药理学注入BDNF蛋白或抗BDNF抗体，我们发现IL中的BDNF，而非前额叶边缘前区（PL）中的BDNF，对恐惧消退而言既必要又充分。此外，我们报告称，IL中的BDNF能够诱导消退较旧的恐惧记忆（14天）以及近期的恐惧记忆（1天）。通过免疫细胞化学方法，我们发现消退训练后腹侧海马体（vHPC）中BDNF增加，但IL或PL中未增加。最后，我们观察到，在恐惧条件化大鼠中，将BDNF注入vHPC会增加IL而非PL神经元的放电频率。这些发现表明，vHPC内由消退诱导的BDNF增加增强了IL靶点的兴奋性，从而支持消退记忆。
