Wang Yimeng, Bai Yang, Xiao Xi, Wang Ling, Wei Ganjiang, Guo Mingkun, Song Xizi, Tian Yutao, Ming Dong, Yang Jiajia, Zheng Chenguang
Academy of Medical Engineering and Translational Medicine, Tianjin University, #92 Weijin Road, Tianjin 300072, China.
Tianjin Key Laboratory of Brain Science and Neuroengineering, Tianjin 300072, China.
Cereb Cortex. 2022 Dec 8;32(24):5580-5596. doi: 10.1093/cercor/bhac037.
The excitatory neurons of the medial prefrontal cortex (mPFC) respond to social stimuli. However, little is known about how the neural activity is altered during social avoidance, and whether it could act as a target of low-intensity focused ultrasound stimulation (LIFUS) to rescue social deficits. The present study aimed to investigate the mechanisms of neuronal activities and inflammatory responses underlying the effect of LIFUS on social avoidance. We found that chronic LIFUS stimulation can effectively improve social avoidance in the defeated mice. Calcium imaging recordings by fiber photometry in the defeated mice showed inhibited ensemble activity during social behaviors. LIFUS instantaneously triggered the mPFC neuronal activities, and chronic LIFUS significantly enhanced their neuronal excitation related to social interactions. We further found that the excessive activation of microglial cells and the overexpression of the inflammation signaling, i.e. Toll-like receptors(TLR4)/nuclear factor-kappaB(NF-КB), in mPFC were significantly inhibited by LIFUS. These results suggest that the LIFUS may inhibit social avoidance behavior by reducing activation of the inflammatory response, increasing neuronal excitation, and protecting the integrity of the neuronal structure in the mPFC. Our findings raised the possibility of LIFUS being applied as novel neuromodulation for social avoidance treatment in neuropsychiatric diseases.
内侧前额叶皮质（mPFC）的兴奋性神经元对社会刺激有反应。然而，对于社交回避期间神经活动如何改变，以及它是否可以作为低强度聚焦超声刺激（LIFUS）的靶点以挽救社交缺陷，人们知之甚少。本研究旨在探讨LIFUS对社交回避影响的神经元活动和炎症反应机制。我们发现，慢性LIFUS刺激可有效改善战败小鼠的社交回避行为。通过纤维光度法对战败小鼠进行钙成像记录显示，社交行为期间整体活动受到抑制。LIFUS可瞬间触发mPFC神经元活动，慢性LIFUS可显著增强与社交互动相关的神经元兴奋性。我们进一步发现，LIFUS可显著抑制mPFC中微胶质细胞的过度激活以及炎症信号即Toll样受体（TLR4）/核因子-κB（NF-κB）的过表达。这些结果表明，LIFUS可能通过减少炎症反应激活、增加神经元兴奋性以及保护mPFC中神经元结构的完整性来抑制社交回避行为。我们的研究结果提出了LIFUS作为神经精神疾病社交回避治疗的新型神经调节方法的可能性。
