Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT_1A antagonist. Finally, we demonstrate that activation of 5-HT_1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT_1A receptors under naturalistic conditions.

中文翻译：

---

5-羟色胺输入到背侧BNST以5-HT1A受体依赖性方式调节焦虑。

5-羟色胺（5-HT）神经元从整个大脑的缝核突出，并在其中起到维持体内稳态的作用。在这里，我们研究5-HT输入到终端纹状体（BNST）的床核中，这是扩展杏仁核的主要细分，已提出调节人体和啮齿类动物对焦虑发生环境的反应。虽然BNST的背侧部分（dBNST）接受密集的5-HT神经支配，但尚不清楚dBNST中的5-HT是否正常调节焦虑以及如何正常调节焦虑。使用光遗传学，我们证明了在dBNST中激活5-HT末端可降低高度焦虑的环境中的焦虑。进一步的分析表明，在不太焦虑的环境中，对进入dBNST的5-HT输入的光遗传学抑制作用增加了焦虑。我们发现5-HT主要使dBNST神经元超极化，_1A拮抗剂。最后，我们证明激活dBNST中的5-HT _1A受体对于对进入dbNST的5-HT输入进行光遗传刺激后观察到的抗焦虑作用是必要的。这些数据表明，在自然条件下，dBNST中的5-HT释放通过5-HT _1A受体调节了焦虑样行为。