Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.

中文翻译：

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mPFC 中的伽玛振荡功能导致 Neuroligin 3 R451C 敲入小鼠的社交缺陷

Neuroligins (NL) 对于突触形成和功能至关重要。NL3 R451C 是一种与自闭症相关的突变。NL3 R451C 敲入 (KI) 小鼠表现出自闭症行为异常，包括社交新奇缺陷。然而，无论是涉及社会新颖性的大脑区域还是潜在的机制都不清楚。在这里，我们发现快速尖峰中间神经元的兴奋性降低和内侧前额叶皮层（mPFC）的伽马振荡功能障碍，这导致了 KI 小鼠的社交新奇感缺陷。KI 小鼠在社交互动过程中也检测到神经元放电率和相位编码异常。有趣的是，以 40 Hz 频率对 mPFC 中的小白蛋白中间神经元进行光遗传学刺激，以 8 Hz 频率嵌套，可以积极调节小鼠的社交行为，并挽救 KI 小鼠的社交新奇缺陷。我们的研究结果表明，mPFC 中的 γ 振荡功能障碍会导致自闭症患者的社交缺陷，而操纵 mPFC PV 中间神经元可能会逆转成年后的缺陷。