BACKGROUND Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. OBJECTIVES We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. METHODS Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. RESULTS Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the MG→LA or ACx→LA circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. DISCUSSION Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532.

中文翻译：

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小鼠慢性中度噪声暴露后焦虑样行为和神经回路的特征。

背景技术 常见的非创伤性中度噪音越来越多地与焦虑有关。然而，这一过程背后的神经基质仍不清楚。目标我们研究了长期暴露于中等强度噪音导致焦虑样行为的神经回路机制。方法 将小鼠暴露于慢性、中度白噪声 [85 分贝 (dB) 声压级 (SPL)]，每天 4 小时，持续 4 周，以诱发焦虑样行为，通过开放场、高架十字迷宫、灯光进行评估- 暗盒和社交互动测试。使用病毒示踪、免疫荧光共焦成像和脑切片膜片钳记录来表征从听觉脑区到外侧杏仁核的投影。通过清醒小鼠体内多电极和纤维光度测定记录来表征神经元活动。光遗传学和化学遗传学被用来操纵特定的神经回路。结果 长期（4 周）暴露于中度噪音（85 dB SPL，4 小时/天）的小鼠表现出外侧杏仁核 (LA) 的神经元活动更强，并且 LA 在这些小鼠中噪音诱发的焦虑样行为中发挥着关键作用。模型小鼠。病毒追踪表明，LA 接收来自内侧膝状体 (MG) 和听觉皮层 (ACx) 的单突触投射。MG→LA 或 ACx→LA 回路的光遗传学激发会强烈诱发焦虑样行为，而它们的化学遗传学失活则消除了噪声引起的焦虑样行为。此外，长期暴露于中度噪音的小鼠更容易受到急性应激的影响，即使在噪音消失后，洛杉矶的神经元放电也会更多。讨论 暴露于中等噪音（85 dB SPL，4 小时/天）4 周的小鼠与对照组相比表现出行为和生理差异。神经回路机制涉及在长期、中度噪音暴露下，MG 和 ACx 的谷氨酸能神经元对 LA 神经元的更大兴奋，最终促进焦虑样行为。我们的研究结果支持这样的假设：非创伤性噪音污染是一个潜在严重但未被认识到的公共卫生问题。https://doi.org/10.1289/EHP12532。