浙江大学许均瑜等研究人员合作揭示中内侧前额叶皮层-基底外侧杏仁核回路在Shank3 InsG3680敲入小鼠中的焦虑介导作用。相关论文于2024年8月29日在线发表于国际学术期刊《神经科学通报》。

研究人员发现，Shank3 InsG3680敲入（InsG3680^+/+）小鼠基底外侧杏仁核（BLA）锥体神经元（PN）的过度活跃与焦虑的发展有关。电生理结果也显示，BLA PN的兴奋性输入增加，抑制性输入减少。化学遗传学抑制BLA PN的兴奋性可以缓解InsG3680^+/+小鼠的焦虑表型。

进一步研究发现，内侧前额叶皮层（mPFC）对BLA的控制减弱以及光遗传学激活mPFC-BLA通路也有缓解作用，这增加了BLA的前馈抑制。综上所述，这些结果表明，BLA的过度活跃和mPFC-BLA回路的改变与InsG3680^+/+小鼠中的焦虑相关。

据了解，焦虑障碍是自闭症谱系障碍（ASD）的主要症状之一，其共病率约为40%。然而，ASD中焦虑的神经机制尚不明确。

附：英文原文

Title: The Medial Prefrontal Cortex-Basolateral Amygdala Circuit Mediates Anxiety in Shank3 InsG3680 Knock-in Mice

Author: Feng, Jiabin, Wang, Xiaojun, Pan, Meidie, Li, Chen-Xi, Zhang, Zhe, Sun, Meng, Liao, Tailin, Wang, Ziyi, Luo, Jianhong, Shi, Lei, Chen, Yu-Jing, Li, Hai-Feng, Xu, Junyu

Issue&Volume: 2024-08-29

Abstract: Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+ mice.

DOI: 10.1007/s12264-024-01280-5

Source: https://link.springer.com/article/10.1007/s12264-024-01280-5