Ito Wataru, Holmes Andrew, Morozov Alexei
Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia.
Fralin Biomedical Research Institute at VTC Center for Neurobiology Research, Roanoke, Virginia.
Biol Psychiatry Glob Open Sci. 2025 Mar 18;5(4):100484. doi: 10.1016/j.bpsgos.2025.100484. eCollection 2025 Jul.
Socially coordinated threat responses support a group's survival. Given the distinct social roles of each sex, social coordination can differ between males and females and mixed-sex groups. We investigated how the sex composition of mouse dyads affected one form of social coordination, the synchronization of conditioned freezing, and assessed how emotional state and social context influenced synchronization by exposure to stress and altering the partner's familiarity, respectively.
Mice were fear conditioned individually to an auditory stimulus and tested in same- or opposite-sex dyads with familiar or unfamiliar partners. Independent cohorts were tested after 5 minutes of restraint stress or with prefrontal inactivation by muscimol. Time-series data on freezing bouts were used to compute the synchrony index, freezing properties, and state transitions based on a Markov model.
In same-sex dyads, males exhibited higher synchrony than females. State transition analysis revealed sex-specific synchronization strategies: Males maintained a congruent freezing state primarily by following their partners' state transitions, whereas females did so by reversing their own. Stress disrupted synchrony in males, which was prevented by prefrontal inactivation, while stress enhanced synchrony in females. Partner's unfamiliarity reduced synchrony in males but had no effect on females. Conversely, opposite-sex dyads exhibited high levels of synchrony and a unique resilience to stress and unfamiliarity without preferred synchronization strategies.
Mice display sex composition-specific synchronization of threat response and its modulation by stress and social context, providing insights into neuropsychiatric disorders characterized by abnormal threat responses in social contexts with same- and opposite-sex groups.
社会协调的威胁反应有助于群体生存。鉴于两性各自不同的社会角色，社会协调在雄性、雌性以及混合性别的群体中可能存在差异。我们研究了小鼠二元组的性别构成如何影响一种社会协调形式，即条件性僵立反应的同步性，并分别通过施加压力和改变伙伴的熟悉程度来评估情绪状态和社会背景如何影响同步性。
小鼠分别对听觉刺激进行恐惧条件反射训练，并与熟悉或不熟悉的伙伴以同性或异性二元组形式进行测试。独立的实验组在受到5分钟的束缚应激后或用蝇蕈醇使前额叶失活后进行测试。基于马尔可夫模型，使用关于僵立发作的时间序列数据来计算同步指数、僵立特性和状态转换。
在同性二元组中，雄性表现出比雌性更高的同步性。状态转换分析揭示了性别特异性的同步策略：雄性主要通过跟随伙伴的状态转换来维持一致的僵立状态，而雌性则通过逆转自己的状态来实现。应激破坏了雄性的同步性，而前额叶失活可防止这种情况发生，而应激则增强了雌性的同步性。伙伴的不熟悉会降低雄性的同步性，但对雌性没有影响。相反，异性二元组表现出高水平的同步性以及对压力和不熟悉的独特恢复力，且没有偏好的同步策略。
小鼠表现出威胁反应的性别构成特异性同步性及其受压力和社会背景的调节，这为以在同性和异性群体的社会背景中异常威胁反应为特征的神经精神疾病提供了见解。
