The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function
The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function
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DOI：
10.1038/srep23757
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发表时间：
2016-04-07
影响因子：
4.6
通讯作者：
Kim, Hyun
中科院分区：
文献类型：
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作者：
Chung, Sooyoung;Kim, Il Hwan;Kim, Hyun
肌醇1，4，5-三磷酸3-激酶A（IP 3 K-A）是一种富含于脑和神经元中的分子，其通过三磷酸肌醇受体的信号传导调节细胞内钙水平。在本研究中，我们发现IP 3 K-A表达高度富集在杏仁核中央核（CeA），这在哺乳动物的情绪表型的加工和表达中起着关键作用。IP 3 K-A基因的废除改变了杏仁核基因的表达，特别是在参与关键细胞内信号通路的基因和介导恐惧和焦虑相关行为的基因中。与杏仁核基因表达谱的变化一致，IP 3 K-A敲除（KO）小鼠对厌恶刺激表现出更强烈的反应，并且在高架十字迷宫的开放臂中花费的时间更少，表明先天恐惧和焦虑水平较高。除了行为表型，减少兴奋性和抑制性突触后电流和减少的c-Fos免疫反应性在CeA的IP 3 K-A基因敲除小鼠表明，IP 3 K-A有一个深刻的影响基础活动的恐惧和焦虑介导的杏仁核电路。总之，我们的研究结果共同表明，IP 3 K-A通过调节杏仁核中的代谢型受体信号通路和神经活动在调节情感状态中起着重要作用。
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a molecule enriched in the brain and neurons that regulates intracellular calcium levels via signaling through the inositol trisphosphate receptor. In the present study, we found that IP3K-A expression is highly enriched in the central nucleus of the amygdala (CeA), which plays a pivotal role in the processing and expression of emotional phenotypes in mammals. Genetic abrogation of IP3K-A altered amygdala gene expression, particularly in genes involved in key intracellular signaling pathways and genes mediating fear-and anxiety-related behaviors. In agreement with the changes in amygdala gene expression profiles, IP3K-A knockout (KO) mice displayed more robust responses to aversive stimuli and spent less time in the open arms of the elevated plus maze, indicating high levels of innate fear and anxiety. In addition to behavioral phenotypes, decreased excitatory and inhibitory postsynaptic current and reduced c-Fos immunoreactivity in the CeA of IP3K-A KO mice suggest that IP3K-A has a profound influence on the basal activities of fear-and anxiety-mediating amygdala circuitry. In conclusion, our findings collectively demonstrate that IP3K-A plays an important role in regulating affective states by modulating metabotropic receptor signaling pathways and neural activity in the amygdala.