Social Synchronization of Conditioned Fear in Mice Requires Ventral Hippocampus Input to Amygdala

Background: Social organisms synchronize behaviors as an evolutionary-conserved means for thriving. Synchronization under threat, in particular, benefits survival and occurs across species, including humans, but the underlying mechanisms remain unknown, due to the scarcity of the relevant animal models. Here, we developed a rodent paradigm in which mice synchronize classically conditioned fear response and identified an underlying neuronal circuit. Methods: Males and female mice were trained individually in an auditory fear conditioning and then tested 24 h later as dyads allowing unrestricted social interaction during exposure to the conditioned stimulus, under the visible or infrared illumination to eliminate visual cues. The synchronization of the immobility or freezing bouts was quantified by calculating the effect size Cohen’s D for the difference between the actual freezing time overlap and the overlap by chance. The inactivation of the dorsomedial prefrontal cortex, dorsal hippocampus, or ventral hippocampus was achieved by local infusions of muscimol. The chemogenetic disconnection of the hippocampus-amygdala pathway was performed by expressing hM4D(Gi) in the ventral hippocampal neurons and infusing CNO in the amygdala. Results: Mice synchronized cued but not contextual fear. It was higher in males than in females and attenuated in the absence of visible light. Inactivation of the ventral but not dorsal hippocampus or dorsomedial prefrontal cortex abolished fear synchronization. Finally, the disconnection of the hippocampal-amygdala pathway diminished fear synchronization. Conclusions: Mice synchronize expression of conditioned fear relying on the ventral hippocampus-amygdala pathway, suggesting that the hippocampus transmits social information to the amygdala to synchronize threat response.