Amygdala hyper-connectivity in a mouse model of unpredictable early life stress.
Amygdala hyper-connectivity in a mouse model of unpredictable early life stress.
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DOI：
10.1038/s41398-018-0092-z
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发表时间：
2018-02-21
影响因子：
6.8
通讯作者：
Kaffman A
中科院分区：
文献类型：
--
作者：
Johnson FK;Delpech JC;Thompson GJ;Wei L;Hao J;Herman P;Hyder F;Kaffman A
儿童虐待与广泛的精神病理有关，包括在儿童时期出现的焦虑，在许多情况下持续到成年。面对威胁时，杏仁核的激活增加，以及杏仁核与大脑额叶边缘区域（如海马体和前额叶皮层）的异常连接，是在童年遭受虐待的个体中看到的一些最一致的发现。导致这些变化的潜在机制很难在人类身上进行研究，但可以通过早期生活压力的动物模型来阐明。这样的研究在老鼠身上尤其有效，在老鼠身上，精确控制遗传背景和压力范式可以与静息状态功能磁共振成像（rsfMRI）相结合，以绘制调节焦虑的神经回路中的异常连接。为了解决这个问题，我们首先比较了两种早期生活压力模型，有限的床上用品（LB）和不可预测的产后压力（UPS）对幼年和成年小鼠焦虑样行为的影响。我们发现UPS，而不是LB，会导致幼年和成年雄性小鼠的焦虑显著增加。接下来，我们使用rsfMRI来比较对照组和UPS成年雄性小鼠的额叶连通性。我们发现UPS患者的杏仁核-前额叶皮层和杏仁核-海马连通性增加。杏仁核-海马和杏仁核-前额叶皮层的连通性强度与开放性测试和高架迷宫中的焦虑样行为高度相关。这些发现首次将额叶边缘回路的超连通性与小鼠早期生活压力模型中的焦虑增加联系起来，从而对人类的类似发现有了更多的机制理解。
Childhood maltreatment is associated with a wide range of psychopathologies including anxiety that emerge in childhood and in many cases persist in adulthood. Increased amygdala activation in response to threat and abnormal amygdala connectivity with frontolimbic brain regions, such as the hippocampus and the prefrontal cortex, are some of the most consistent findings seen in individuals exposed to childhood maltreatment. The underlying mechanisms responsible for these changes are difficult to study in humans but can be elucidated using animal models of early-life stress. Such studies are especially powerful in the mouse where precise control of the genetic background and the stress paradigm can be coupled with resting-state fMRI (rsfMRI) to map abnormal connectivity in circuits that regulate anxiety. To address this issue we first compared the effects of two models of early-life stress, limited bedding (LB) and unpredictable postnatal stress (UPS), on anxiety-like behavior in juvenile and adult mice. We found that UPS, but not LB, causes a robust increase in anxiety in juvenile and adult male mice. Next, we used rsfMRI to compare frontolimbic connectivity in control and UPS adult male mice. We found increased amygdala–prefrontal cortex and amygdala–hippocampus connectivity in UPS. The strength of the amygdala–hippocampal and amygdala–prefrontal cortex connectivity was highly correlated with anxiety-like behavior in the open-field test and elevated plus maze. These findings are the first to link hyperconnectivity in frontolimbic circuits and increased anxiety in a mouse model of early-life stress, allowing for more mechanistic understanding of parallel findings in humans.
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DOI：
10.1002/cne.22359
发表时间：
2010-07-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Cressman VL;Balaban J;Steinfeld S;Shemyakin A;Graham P;Parisot N;Moore H
通讯作者：
Moore H
影响因子：
8.9
作者：
Chen, Laura P.;Murad, M. Hassan;Zirakzadeh, Ali
通讯作者：
Zirakzadeh, Ali
影响因子：
17.7
作者：
Bogdan, Ryan;Williamson, Douglas E.;Hariri, Ahmad R.
通讯作者：
Hariri, Ahmad R.
影响因子：
15.1
作者：
Delpech, Jean-Christophe;Wei, Lan;Hao, Jin;Yu, Xiaoqing;Madore, Charlotte;Butovsky, Oleg;Kaffman, Arie
通讯作者：
Kaffman, Arie
影响因子：
4.8
作者：
Coohey, Carol
通讯作者：
Coohey, Carol