Stress induces distinct social behavior states encoded by the ventral hippocampus

Abstract

A single, acute traumatic experience can result in a host of negative impacts on behavior, such as increased violence, reduced sociability, and exaggerated fear responses. Despite the large body of research on the neurobiology of stress, we have a poor understanding of how trauma rewires social circuits in the brain. To identify how social circuits are re-organized by stress, we interrogated the role of the ventral hippocampus (VH), a key node for both the orchestration of emotionally-relevant behavior and the integration of sensory information. Using a footshock-based model of traumatic stress, we established that a single exposure to a series of unpredictable, inescapable footshocks was sufficient to negatively alter social behavior, resulting in increased violence and social hesitancy. Critically, we found that stress-induced changes to social behavior engaged neural ensembles in the VH, a critical node in the regulation of emotion states. Using a virally-mediated, activity-dependent cellular tagging approach to label two neural ensembles activated by temporally distinct experiences, we were surprised to find that stress-induced violence and stress-induced social hesitancy recruited largely non-overlapping populations of cells in the VH, in contrast to higher degrees of ensemble overlap in unstressed control mice, suggesting that stress biases the brain towards stronger differentiation of distinct social states. Additionally, we found that activity of VH neurons was required for stress-induced aggression. Finally, we found that stress-induced changes to social behaviors and VH activity profiles could be reversed by the introduction of social buffering post-stress. Collectively, our findings suggest that stress drives the VH to dissociably encode specific behavioral states, rather than a single state of negative valence, consistent with a role for multiple structures and distributed ensembles in the modulation of traumatic stress.