Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning.
Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning.
复制标题
杏仁核Crh表达神经元的全基因组翻译谱揭示了CREB在恐惧消退学习中的作用
DOI：
10.1038/s41467-020-18985-6
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发表时间：
2020-10-14
影响因子：
16.6
通讯作者：
Ressler KJ
中科院分区：
文献类型：
--
作者：
McCullough KM;Chatzinakos C;Hartmann J;Missig G;Neve RL;Fenster RJ;Carlezon WA Jr;Daskalakis NP;Ressler KJ
恐惧和灭绝学习是由特定神经回路中的分子变化引起的适应性过程。中央杏仁核（CeA）中表达促肾上腺皮质激素释放激素基因（Crh）的神经元参与威胁调节，但对介导适应性学习的细胞类型特异性基因通路知之甚少。我们使用翻译核糖体亲和纯化（TRAP）和RNAseq对小鼠恐惧条件反射或消退后CeA Crh表达细胞（Crh神经元）的转录组进行了分析。差异基因表达和共表达网络分析确定了不同的网络激活或抑制恐惧与灭绝。上游调节因子分析表明，灭绝与CREB表达减少，和病毒载体诱导的Crh神经元CREB表达增加恐惧的表达和抑制灭绝。这些研究结果表明，CREB，CeA Crh神经元内，可能作为一个分子开关，调节恐惧的表达和灭绝。细胞类型特异性翻译分析可能会为理解和治疗与压力相关的精神疾病提供有用的靶点。恐惧和恐惧消退学习是动态的。这些动态变化是由转录变化强调。在这里，作者分析了杏仁核中的Crh神经元，并确定了相关的基因网络。
Fear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness. Fear and fear extinction learning are dynamic. These dynamic changes are underlined by transcriptional changes. Here, the authors translationally profiled Crh neurons in the amygdala and and identified relevant gene networks.
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影响因子：
12.8
作者：
Babaev O;Piletti Chatain C;Krueger-Burg D
通讯作者：
Krueger-Burg D
DOI：
10.1038/s41583-018-0039-7
发表时间：
2018-09
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Fenster RJ;Lebois LAM;Ressler KJ;Suh J
通讯作者：
Suh J
影响因子：
16.2
作者：
Gozzi, Alessandro;Jain, Apar;Bifone, Angelo
通讯作者：
Bifone, Angelo
影响因子：
25
作者：
Gelernter, Joel;Sun, Ning;Stein, Murray B.
通讯作者：
Stein, Murray B.
影响因子：
2.7
作者：
Dedic N;Chen A;Deussing JM
通讯作者：
Deussing JM