Peng Xiaoqi, Mao Yunfeng, Liu Yehao, Dai Qian, Tai Yingju, Luo Bin, Liang Yue, Guan Ruirui, Zhou Wenjie, Chen Lin, Zhang Zhi, Shen Guoming, Wang Haitao
Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
CNS Neurosci Ther. 2024 Mar;30(3):e14674. doi: 10.1111/cns.14674.
Long-term non-traumatic noise exposure, such as heavy traffic noise, can elicit emotional disorders in humans. However, the underlying neural substrate is still poorly understood.
We exposed mice to moderate white noise for 28 days to induce anxiety-like behaviors, measured by open-field, elevated plus maze, and light-dark box tests. In vivo multi-electrode recordings in awake mice were used to examine neuronal activity. Chemogenetics were used to silence specific brain regions. Viral tracing, immunofluorescence, and confocal imaging were applied to define the neural circuit and characterize the morphology of microglia.
Exposure to moderate noise for 28 days at an 85-dB sound pressure level resulted in anxiety-like behaviors in open-field, elevated plus maze, and light-dark box tests. Viral tracing revealed that fibers projecting from the auditory cortex and auditory thalamus terminate in the lateral amygdala (LA). A noise-induced increase in spontaneous firing rates of the LA and blockade of noise-evoked anxiety-like behaviors by chemogenetic inhibition of LA glutamatergic neurons together confirmed that the LA plays a critical role in noise-induced anxiety. Noise-exposed animals were more vulnerable to anxiety induced by acute noise stressors than control mice. In addition to these behavioral abnormalities, ionized calcium-binding adaptor molecule 1 (Iba-1)-positive microglia in the LA underwent corresponding morphological modifications, including reduced process length and branching and increased soma size following noise exposure. Treatment with minocycline to suppress microglia inhibited noise-associated changes in microglial morphology, neuronal electrophysiological activity, and behavioral changes. Furthermore, microglia-mediated synaptic phagocytosis favored inhibitory synapses, which can cause an imbalance between excitation and inhibition, leading to anxiety-like behaviors.
Our study identifies LA microglial activation as a critical mediator of noise-induced anxiety-like behaviors, leading to neuronal and behavioral changes through selective synapse phagocytosis. Our results highlight the pivotal but previously unrecognized roles of LA microglia in chronic moderate noise-induced behavioral changes.
长期非创伤性噪声暴露，如交通噪音，可引发人类情绪障碍。然而，其潜在的神经基质仍知之甚少。
我们将小鼠暴露于中度白噪声中28天，以诱导焦虑样行为，通过旷场试验、高架十字迷宫试验和明暗箱试验进行测量。使用清醒小鼠体内多电极记录来检测神经元活动。采用化学遗传学方法使特定脑区沉默。应用病毒示踪、免疫荧光和共聚焦成像来定义神经回路并表征小胶质细胞的形态。
在85分贝声压水平下暴露于中度噪声28天，导致旷场试验、高架十字迷宫试验和明暗箱试验中出现焦虑样行为。病毒示踪显示，从听觉皮层和听觉丘脑投射的纤维终止于外侧杏仁核（LA）。噪声诱导的LA自发放电率增加以及通过化学遗传学抑制LA谷氨酸能神经元对噪声诱发的焦虑样行为的阻断共同证实，LA在噪声诱导的焦虑中起关键作用。与对照小鼠相比，暴露于噪声的动物更容易受到急性噪声应激源诱导的焦虑影响。除了这些行为异常外，LA中离子钙结合衔接分子1（Iba-1）阳性小胶质细胞发生了相应的形态学改变，包括噪声暴露后突起长度和分支减少以及胞体大小增加。用米诺环素治疗以抑制小胶质细胞，可抑制小胶质细胞形态、神经元电生理活动和行为变化中与噪声相关的改变。此外，小胶质细胞介导的突触吞噬作用有利于抑制性突触，这可能导致兴奋与抑制之间的失衡，从而导致焦虑样行为。
我们的研究确定LA小胶质细胞激活是噪声诱导的焦虑样行为的关键介质，通过选择性突触吞噬导致神经元和行为变化。我们的结果突出了LA小胶质细胞在慢性中度噪声诱导的行为变化中关键但以前未被认识的作用。
