Htr2a-Expressing Cells in the Central Amygdala Control the Hierarchy between Innate and Learned Fear
Htr2a-Expressing Cells in the Central Amygdala Control the Hierarchy between Innate and Learned Fear
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DOI：
10.1016/j.cell.2015.10.047
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发表时间：
2015-11-19
期刊：
影响因子：
64.5
通讯作者：
Kobayakawa, Ko
中科院分区：
文献类型：
--
作者：
Isosaka, Tomoko;Matsuo, Tomohiko;Kobayakawa, Ko
恐惧是由涉及不同途径的先天机制和后天机制引起的。在这里，我们使用嗅觉介导的先天恐惧与后天恐惧范例来研究这些途径是如何整合的。值得注意的是，先天恐惧刺激的先呈现会抑制习得性冻结反应，但反之则不然。全脑图谱和药理学筛选表明，中央杏仁核 (CeA) 中表达 5-羟色胺 2A 受体 (Htr2a) 的细胞控制先天性冻结和后天性冻结，但方向相反。自由活动小鼠的体内纤维光度分析表明，先天而非后天的恐惧刺激抑制了表达 Htr2a 的 CeA 细胞的活性。这些细胞的人工失活上调了先天性冻结反应并下调了习得性冻结反应。因此，表达 Htr2a 的 CeA 细胞充当等级生成器，优先考虑先天恐惧而不是后天恐惧。
Fear is induced by innate and learned mechanisms involving separate pathways. Here, we used an olfactory- mediated innate-fear versus learned-fear paradigm to investigate how these pathways are integrated. Notably, prior presentation of innatefear stimuli inhibited learned-freezing response, but not vice versa. Whole-brain mapping and pharmacological screening indicated that serotonin-2A receptor (Htr2a)-expressing cells in the central amygdala (CeA) control both innate and learned freezing, but in opposing directions. In vivo fiber photometry analyses in freely moving mice indicated that innate but not learned-fear stimuli suppressed the activity of Htr2a-expressing CeA cells. Artificial inactivation of these cells upregulated innate-freezing response and downregulated learned-freezing response. Thus, Htr2a-expressing CeA cells serve as a hierarchy generator, prioritizing innate fear over learned fear.