Stress-related Memories Disrupt Sociability and Associated Patterning of Hippocampal Activity: a Role of Hilar Oxytocin Receptor-positive Interneurons

In susceptible individuals, memories of stressful experiences can give rise to debilitating socio-affective symptoms. This occurs even when the ability to retrieve such memories is limited, as seen in patients suffering from traumatic amnesia. We therefore hypothesized that the encoding, rather than retrieval, mechanisms of stress-related memories underlie their impact on social and emotional behavior. To test this hypothesis, we used combinations of stress-enhanced and state-dependent fear conditioning, which engage different encoding mechanisms for the formation of stress-related memories. We found that the encoding of stress-enhanced state-dependent memories robustly and sex specifically impairs sociability in male mice and disrupts the asymmetry of dentate gyrus (DG)/CA3 activity accompanying social interactions. These deficits were restored by chemogenetic inactivation of oxytocin receptor-positive interneurons localized in the hilus (Oxtr-HI), and by inactivation of dorsohippocampal efferents to the caudal lateral septum. Together, our data suggest that disrupted patterning of dorsohippocampal DG/CA3 activity underlies stress-induced sociability deficits, and that Oxtr-HI can be a cellular target for improving these deficits.