Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.
Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.
复制标题
DOI：
10.1016/j.biopsych.2014.11.014
复制
发表时间：
2015-08-01
影响因子：
10.6
通讯作者：
Shansky RM
中科院分区：
文献类型：
--
作者：
Gruene TM;Roberts E;Thomas V;Ronzio A;Shansky RM
从前额叶皮层边缘下区到杏仁核的神经投射对条件恐惧消退的维持具有重要意义。这条通路上的神经元表现出一种独特的结构可塑性模式，这种模式是性别依赖的，但这些神经元的形态特征与雄性和雌性成功灭绝之间的关系尚不清楚。利用经典的线索恐惧条件反射和灭绝模式，我们在大型雄性和雌性大鼠队列中发现了在灭绝恢复测试中表现出高（HF）或低（LF）冻结水平的两性亚群，分别代表灭绝维持失败或成功。然后，我们将逆行示踪与荧光细胞内显微注射相结合，对这些组中投射到基底外侧杏仁核（BLA）的IL神经元进行3D重建。HF/LF男性表现出神经解剖学上的差异，而在HF和LF女性中没有观察到。对恐惧条件反射和消退过程中的行为进行回顾性分析发现，尽管冻结行为没有性别差异，但雄性在消退过程中出现HF/LF表型，而雌性在恐惧条件反射过程中出现HF/LF表型，这与IL-BLA神经元无关。我们的研究结果表明，成功或失败的灭绝维持的神经过程可能是性别特异性的。这些发现不仅与未来关于恐惧调节和消退的性别差异的基础研究有关，而且与基于暴露的临床疗法有关，这种疗法的前提与恐惧消退相似，主要用于治疗女性比男性更常见的疾病。
The neural projections from the infralimbic region of the prefrontal cortex (IL) to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphological characteristics of these neurons and successful extinction in males and females is unknown. Using classic cued fear conditioning and extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We then combined retrograde tracing with fluorescent intracellular microinjections to perform 3D reconstructions of IL neurons that project to the basolateral amygdala (BLA) in these groups. HF/LF males exhibited neuroanatomical distinctions that were not observed in HF vs. LF females. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF/LF phenotypes emerged in males during extinction, but in females during fear conditioning, which does not involve IL-BLA neurons. Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are not only relevant to future basic research on sex differences in fear conditioning and extinction, but also to exposure-based clinical therapies, which are similar in premise to fear extinction, and which are primarily used to treat disorders that are more common in women than in men.
登录
查看更多内容
影响因子：
2.7
作者：
Gruene, Tina M.;Lipps, Jennifer;Shansky, Rebecca M.
通讯作者：
Shansky, Rebecca M.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.3
作者：
Milad, M. R.;Zeidan, M. A.;Goldstein, J. M.
通讯作者：
Goldstein, J. M.
影响因子：
56.9
作者：
Matsuo, Naoki;Reijmers, Leon;Mayford, Mark
通讯作者：
Mayford, Mark
影响因子：
64.8
作者：
Milad, MR;Quirk, GJ
通讯作者：
Quirk, GJ