Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early-Life Anxious Temperament.
Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early-Life Anxious Temperament.
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灵长类动物杏仁核中央核的转录谱分析，以了解早期生活焦虑气质的分子基础。
DOI：
10.1016/j.biopsych.2020.05.009
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发表时间：
2020-10-15
影响因子：
10.6
通讯作者：
Kalin NH
中科院分区：
文献类型：
--
作者：
Kovner R;Souaiaia T;Fox AS;French DA;Goss CE;Roseboom PH;Oler JA;Riedel MK;Fekete EM;Fudge JL;Knowles JA;Kalin NH
表现出极端焦虑气质（AT）的儿童患焦虑和抑郁的风险增加。我们先前在年轻恒河猴中的机制和神经成像工作将杏仁核（Ce）的中央核与AT及其潜在的神经回路联系起来。在这里，我们使用激光捕获显微镜和RNA测序在47个年轻的恒河猴研究AT的分子基础，专注于外侧Ce（CeL）神经元。RNA测序鉴定了许多AT相关的CeL转录本，我们在不同的猴子样本中使用免疫荧光（n=3）和追踪（n=2）方法来检查表达这些转录本之一的神经元的表达、分布和投射模式。我们发现了555个AT相关的转录本，其中14个被证实具有高统计学置信度（FDR<0.1），包括蛋白激酶C型δ（PKCδ），这是一种涉及啮齿动物威胁处理的CeL微电路细胞标记物。我们对恒河猴细胞中的PKCδ神经元进行了表征，将其分布与小鼠的分布进行了比较，并证明了这些神经元的一个子集投射到终纹的侧背床核（BSTLd）。这些发现表明CeL PKCδ与灵长类动物焦虑相关，提供了CeL至BSTLd回路的证据，该回路可能与理解人类焦虑相关，并指出该回路中的特定分子可作为焦虑症的潜在治疗靶点。
Children exhibiting extreme anxious temperament (AT) are at an increased risk to develop anxiety and depression. Our previous mechanistic and neuroimaging work in young rhesus monkeys links the central nucleus of the amygdala (Ce) to AT and its underlying neural circuit. Here, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys to investigate AT’s molecular underpinnings by focusing on lateral Ce (CeL) neurons. RNA sequencing identified numerous AT-related CeL transcripts and we used immunofluorescence (n=3) and tract-tracing (n=2) methods in a different sample of monkeys to examine the expression, distribution, and projection pattern of neurons expressing one of these transcripts. We found 555 AT-related transcripts, of which 14 were confirmed with high statistical confidence (FDR<0.1), including protein kinase C type-delta (PKCδ), a CeL microcircuit cell marker implicated in rodent threat processing. We characterized PKCδ neurons in the rhesus CeL, compared its distribution to that of the mouse, and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus of the stria terminalis (BSTLd). These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to BSTLd circuit that may be relevant to understanding human anxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.
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DOI：
10.1097/chi.0b013e3181ae09df
发表时间：
2009-09
影响因子：
13.3
作者：
Chronis-Tuscano A;Degnan KA;Pine DS;Perez-Edgar K;Henderson HA;Diaz Y;Raggi VL;Fox NA
通讯作者：
Fox NA
影响因子：
64.8
作者：
Ciocchi, Stephane;Herry, Cyril;Luethi, Andreas
通讯作者：
Luethi, Andreas
影响因子：
3.7
作者：
Berbari NF;Malarkey EB;Yazdi SM;McNair AD;Kippe JM;Croyle MJ;Kraft TW;Yoder BK
通讯作者：
Yoder BK
影响因子：
25
作者：
Cai, Haijiang;Haubensak, Wulf;Anthony, Todd E.;Anderson, David J.
通讯作者：
Anderson, David J.
影响因子：
2.5
作者：
CASSELL, MD;GRAY, TS
通讯作者：
GRAY, TS