Datasets-Medial Prefrontal Cortex Neurons Integrate Amygdala and Hypothalamic Oxytocin Signals to Mediate Stress-Induced Social Alterations

The medial prefrontal cortex (mPFC), a critical hub for social regulation, is highly vulnerable to stress. While mPFC dysfunction underlies stress-induced social alterations, the precise circuit mechanisms underlying remain elusive. Given mPFC’s integration of stress signals from key nodes like the basolateral amygdala (BLA) and paraventricular hypothalamus (PVN), we hypothesized that enhanced BLA and PVN inputs disrupts mPFC’s circuit dynamics, mediating social alterations after stress exposure. Here, using longitudinal in vivo Ca²⁺ imaging during repeated restraint stress, we observed post-stress mPFC hypoactivity, impaired pattern decorrelation and disrupted population coding for social discrimination following both acute and chronic stress. Further combining circuit-specific optogenetics, we revealed that the mPFC dysfunction arise from convergent potentiation of dual inhibitory circuits, including the BLA glutamatergic inputs activating GABAergic neurons and the PVN oxytocinergic projections activating OXTR⁺ GABAergic interneurons. Critically, suppressing either circuit rescued mPFC hypoactivity, restored its encoding for social discrimination, and normalized social performance in stressed mice. Together, these findings establish a unified circuit pathology wherein BLA and PVN hyperactivity converts environmental stress into social alterations, by disrupting the downstream mPFC's activity dynamics, coactivity pattern, and population coding essential for social discrimination.

内侧前额叶皮层（medial prefrontal cortex, mPFC）是社会调节的关键枢纽，且极易受应激影响。尽管应激诱导的社会行为改变的核心病理基础为mPFC功能障碍，但其确切的环路机制仍未阐明。鉴于mPFC可整合来自基底外侧杏仁核（basolateral amygdala, BLA）、下丘脑室旁核（paraventricular hypothalamus, PVN）等关键脑区的应激信号，我们提出假设：BLA与PVN的输入增强会破坏mPFC的环路动力学，进而介导应激暴露后的社会行为改变。本研究通过在重复性束缚应激过程中开展纵向在体钙离子成像，观察到急性与慢性应激后均出现mPFC低活性、社会辨别的模式去相关功能受损以及群体编码紊乱。进一步结合环路特异性光遗传学技术，我们揭示mPFC功能障碍源于双重抑制环路的会聚性强化：即BLA的谷氨酸能输入激活γ-氨基丁酸能神经元，以及PVN的催产素能投射激活催产素受体阳性（OXTR⁺）的γ-氨基丁酸能中间神经元。至关重要的是，抑制任一环路均可挽救应激小鼠的mPFC低活性，恢复其社会辨别编码功能，并使应激小鼠的社会行为表现恢复至正常水平。综上，本研究确立了一套统一的环路病理机制：BLA与PVN的过度激活通过破坏下游mPFC的活动动力学、协同活动模式以及社会辨别所必需的群体编码，将环境应激转化为社会行为改变。