Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

DIFFERENTIAL OXYTOCIN RECEPTOR SIGNALING DRIVES THE REVERSAL OF SOCIAL TRAUMA-INDUCED AVOIDANCE IN MICE Rohit Menon University of Regensburg, Department of Behavioral and Molecular Neurobiology, Regensburg, Germany Successfully navigating social situations is an essential survival skill for mammals. Oxytocin (OXT) signaling in the lateral septum (LS) is a critical regulator of social behavior, but its underlying neural mechanisms remain poorly understood. In our study, we leverage the operant conditioning-based social fear conditioning paradigm to examine the role of OXT signaling in the LS in regulating recovery from social trauma. First, we show that OXT receptor (OXTR)- expressing neurons are enriched in the caudal LS (LSc) and exhibit pronounced activation during social interaction in the extinction phase following social fear acquisition (i.e., social trauma), indicating that the valence of the social stimulus is critical for activating the OXTR-expressing LS neurons (LS OXTR ). A temporally precise analysis of LS OXTR activity revealed their heightened inhibition at the exact timepoint of social interaction in mice with successful extinction (Responders: Res), while such modulation is absent in mice with unsuccessful extinction (Non responders: Nres). Interestingly, LS OXTR neurons of NRes mice are activated right after social fear extinction in comparison to the Res mice. In all mice, chemogenetic inhibition of LS OXTR disrupts social fear extinction, whereas optogenetic stimulation has no effect, suggesting that the abovementioned temporal modulation is essential for successful extinction. Moreover, pharmacological activation of OXT signaling using synthetic OXT, TGOT (a complete OXTR agonist), or atosiban (a selective OXTR-Gi agonist) facilitates extinction of social fear. These findings indicate that precise temporal inhibition of LS OXTR activity driven by OXTR-coupled Gi signaling is critical for adaptive social behavior, positioning OXT signaling in the LS as a key calibrator of social valence.

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