Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear.
Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear.
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背侧被盖中间神经元亚型相反地调节嗅觉线索引起的先天恐惧。
DOI：
10.1038/nn.4208
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发表时间：
2016
影响因子：
25
通讯作者：
Wang Hao
中科院分区：
文献类型：
--
作者：
Yang Hongbin;Yang Junhua;Xi Wang;Hao Sijia;Luo Benyan;He Xiaobin;Zhu Liya;Lou Huifang;Yu Yan-Qin;Xu Fuqiang;Duan Shumin;Wang Hao
天生的恐惧在动物的生存中起着至关重要的作用。与条件恐惧不同，先天恐惧背后的神经回路在很大程度上是未知的。研究发现，小鼠捕食者气味剂三甲基噻唑啉（TMT）特异性激活了侧背被盖（LDT）和侧缰（LHb）。使用光遗传学选择性刺激下dt中的gaba能神经元立即产生恐惧样反应（冻结，心率加快和血清皮质酮增加），而长时间刺激引起焦虑样行为。值得注意的是，尽管选择性刺激小白蛋白（PV）阳性的中间神经元同样会诱导恐惧样反应，但刺激生长抑素阳性的中间神经元或抑制LDT中的PV神经元会抑制tmt诱导的恐惧样反应，而不会影响条件恐惧。最后，LHb谷氨酸能输入LDT中间神经元的激活足以产生类似恐惧的反应。因此，LHb-LDT通路在调节嗅觉线索诱导的先天恐惧中很重要。我们的结果为焦虑障碍的治疗干预提供了一个潜在的目标。
Innate fear has a critical role in survival of animals. Unlike conditioned fear, the neuronal circuitry underlying innate fear is largely unknown. We found that the laterodorsal tegmentum (LDT) and lateral habenula (LHb) are specifically activated by the mouse predator odorant trimethylthiazoline (TMT). Using optogenetics to selectively stimulate GABAergic neurons in the LDT immediately produced fear-like responses (freezing, accelerated heart rate and increased serum corticosterone), whereas prolonged stimulation caused anxiety-like behaviors. Notably, although selective stimulation of parvalbumin (PV)-positive interneurons similarly induced fear-like responses, stimulation of somatostatin-positive interneurons or inhibition of PV neurons in the LDT suppressed TMT-induced fear-like responses without affecting conditioned fear. Finally, activation of LHb glutamatergic inputs to LDT interneurons was sufficient to generate fear-like responses. Thus, the LHb-LDT pathway is important for regulating olfactory cue–induced innate fear. Our results provide a potential target for therapeutic intervention for anxiety disorder.