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<p>Dysfunction in social interactions is a core symptom of autism spectrum disorder (ASD). Nevertheless, the neural mechanisms underlying social deficits in ASD are poorly understood. By integrating electrophysiological, in vivo fiber photometry, viral-mediated tracing, optogenetic and pharmacological stimulation, we show reduced intrinsic excitability and hypoactivity of SOM interneurons in medial prefrontal cortex (mPFC) in <i>Magel2-</i>deficient mice, an established ASD model, were required to social defects. Chemogenetic inhibition of mPFC SOM-containing interneurons resulted in reduced social interaction in wild-type <i>Magel2</i> mice. These sociability deficits can be rescued by optogenetic activation by excitability of SOM in the mPFC and mPFC<sup>SOM</sup>-LS inhibitory pathway in <i>Magel 2</i> knockout mice. These results demonstrate the hypoactivity for SOM action in the mPFC in social impairments, and suggest targeting this mechanism that may prove therapeutically beneficial for mitigating social behavioral disturbances observed in ASD.</p>

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Somatostatin-expressing interneurons of prefrontal cortex modulate social deficits in the Magel2 mouse model of autism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月11日

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  • Xiaona Wang,
  • Mengyuan Chen,
  • Daoqi Mei,
  • Shengli Shi,
  • Jisheng Guo,
  • Chao Gao,
  • Qi Wang,
  • Shuai Zhao,
  • Xingxue Yan,
  • Huichun Zhang,
  • Yanli Wang,
  • Bin Guo,
  • Yaodong Zhang

摘要

Dysfunction in social interactions is a core symptom of autism spectrum disorder (ASD). Nevertheless, the neural mechanisms underlying social deficits in ASD are poorly understood. By integrating electrophysiological, in vivo fiber photometry, viral-mediated tracing, optogenetic and pharmacological stimulation, we show reduced intrinsic excitability and hypoactivity of SOM interneurons in medial prefrontal cortex (mPFC) in Magel2-deficient mice, an established ASD model, were required to social defects. Chemogenetic inhibition of mPFC SOM-containing interneurons resulted in reduced social interaction in wild-type Magel2 mice. These sociability deficits can be rescued by optogenetic activation by excitability of SOM in the mPFC and mPFCSOM-LS inhibitory pathway in Magel 2 knockout mice. These results demonstrate the hypoactivity for SOM action in the mPFC in social impairments, and suggest targeting this mechanism that may prove therapeutically beneficial for mitigating social behavioral disturbances observed in ASD.