BACKGROUND Both the clinical and preclinical studies have suggested embryonic or infant exposure to ketamine, a general anesthetic, pose a great threat to the developing brain. However, it remains unclear how ketamine may contribute to the brain dysfunctions. METHODS A mouse model of prenatal exposure to ketamine was generated by i.m. injection and continuous i.p. infusion of pregnant mice. Open field test and elevated plus maze test were used to analyze the behavioral alterations induced by ketamine. Immunostaining by c-Fos was used to map the neuron activity. Chemogenetic modulation of the neurons was used to rescue the abnormal neuron activity and behaviors. RESULTS Here we show that mice prenatally exposed to ketamine displayed anxiety-like behaviors during adulthood, but not during puberty. C-Fos immunostaining identified abnormal neuronal activity in Bed Nucleus of the Stria Terminalis, the silencing of which by chemogenetics restores the anxiety-like behaviors. CONCLUSIONS Taken together, these results demonstrate a circuitry mechanism of ketamine-induced anxiety-like behaviors.

中文翻译：

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产前暴露于氯胺酮会导致终端纹状体床核的焦虑样行为和功能障碍。

背景技术临床和临床前研究均表明，胚胎或婴儿接触氯胺酮（全麻）对发育中的大脑构成了巨大威胁。但是，氯胺酮如何导致脑功能障碍仍不清楚。方法通过im注射和腹腔内连续输注妊娠小鼠，建立了产前氯胺酮暴露的小鼠模型。使用开场试验和高架迷宫试验来分析氯胺酮引起的行为改变。使用c-Fos免疫染色来绘制神经元活动图。神经元的化学生成调节被用来挽救异常的神经元活动和行为。结果在这里，我们显示了出生前接触氯胺酮的小鼠在成年期间表现出焦虑样行为，而在青春期则没有。C-Fos免疫染色确定了纹状体床核中异常的神经元活性，通过化学遗传学使之沉默可恢复焦虑样行为。结论综上所述，这些结果证明了氯胺酮诱导的焦虑样行为的电路机制。