The ability to detect conspecific’s distress is crucial for animal survival. In rodent models, observational fear (OF) occurs when one animal perceives another fear related negative emotions, which may model certain behaviors caused by witnessing traumatic experiences in humans. Anterior cingulate cortex (ACC) has been showed to play a crucial role in OF. However, cellular and neural circuit basis relating to ACC governing OF is poorly understood. Here, we used Designer Receptor Exclusively Activated by a Designer Drug (DREADD) system to investigate the cell type specific circuit mechanism of ACC in OF. Firstly, inhibitory hM4D (Gi) designer receptor together with clozapine N-oxide (CNO) injection was applied to inactivate ACC neurons in the observer mice. We found that, chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice. Next, combining PV-ires-Cre mice and Cre-dependent DREADD system, we selectively targeted the ACC parvalbumin (PV) interneurons with the excitatory hM3D (Gq) designer receptor. Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice, while had no effect on freezing response in the demonstrator mice. Finally, monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus (MD) and the ventromedial thalamic nucleus (VM), both known for their roles in OF. Taken together, these findings reveal that ACC activation is important for OF, during which PV interneurons in ACC play an important regulatory role. Abnormal function of ACC PV interneurons might contribute to the pathology of empathy- deficits related diseases, such as autism and schizophrenia.

检测同种动物痛苦的能力对于动物的生存至关重要。在啮齿动物模型中，当一只动物感知到另一种与恐惧相关的负面情绪时，就会发生观察性恐惧 (OF)，这可能会模拟因目睹人类创伤经历而导致的某些行为。前扣带皮层 (ACC) 已被证明在 OF 中起着至关重要的作用。然而，与 ACC 管理 OF 相关的细胞和神经回路基础知之甚少。在这里，我们使用由设计药物 (DREADD) 系统独家激活的设计受体来研究 OF 中 ACC 的细胞类型特异性回路机制。首先，抑制性 hM4D (Gi) 设计受体与氯氮平 N-氧化物 (CNO) 注射液一起用于灭活观察小鼠的 ACC 神经元。我们发现，ACC 的化学遗传学抑制导致观察小鼠的冷冻反应降低。接下来，结合 PV-ires-Cre 小鼠和 Cre 依赖性 DREADD 系统，我们选择性地将 ACC 小清蛋白 (PV) 中间神经元与兴奋性 hM3D (Gq) 设计器受体结合起来。CNO 注射后 ACC PV 中间神经元的激活降低了观察小鼠的冻结反应，而对示范小鼠的冻结反应没有影响。最后，单突触狂犬病逆行追踪显示，ACC PV 中间神经元接收来自丘脑背内侧核 (MD) 和丘脑腹内侧核 (VM) 的输入，这两者都以其在 OF 中的作用而闻名。总之，这些发现表明 ACC 激活对 OF 很重要，在此期间 ACC 中的 PV 中间神经元起着重要的调节作用。