Fear Synchrony of Mouse Dyads: Interaction of Sex Composition and Stress

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.