Furthermore, in this model, stress-related fear memories seem to be inhibited by cortical mechanisms and preferentially processed by hippocampal–lateral septal (LS) circuits 14. Although such memories are normally not accessible to retrieval, their presence can be demonstrated when mice are tested in the presence of the drug 14, 15. State-dependent memory is readily induced in mice trained on gaboxadol (GBX), an agonist of extrasynaptic GABA AR 16 that enhances tonic inhibition in the DG 17. Whereas increasing stress exposure strengthens the encoding of fear-inducing memory 9, 10, 11, 12, 13, state-dependent encoding restricts memory access to specific brain states 14, 15. Rodent models of stress-enhanced state-dependent fear conditioning (S-SDFC) and state-dependent fear conditioning (SDFC) allow studying the impact of stress-related memories on social behavior. ![]() Accordingly, abnormal functioning of episodic memory circuits, especially the hippocampus, has been found in both patient populations 7, 8, and additionally includes cortico-hippocampal inhibition in patients suffering from traumatic amnesia 8. Interestingly, these symptoms are found both in patients suffering from post-traumatic stress disorder, who persistently retrieve such memories 4, and in patients suffering from dissociative amnesia, whose access to such memories is partially or completely blocked 5, 6. In susceptible individuals, autobiographical (episodic) memories of intensely stressful experiences can have debilitating consequences on social and emotional behavior and thus lead to social dysfunction, anxiety, or depression 1, 2, 3. 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. 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. 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. 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 therefore hypothesized that the encoding, rather than retrieval, mechanisms of stress-related memories underlie their impact on social and emotional behavior. This occurs even when the ability to retrieve such memories is limited, as seen in patients suffering from traumatic amnesia. In susceptible individuals, memories of stressful experiences can give rise to debilitating socio-affective symptoms.
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