Social buffering-mediated fear response modulation: Investigating synaptic activity changes in the prelimbic cortex of the medial prefrontal cortex.

Social buffering is a phenomenon in which stress is ameliorated when the subject is accompanied by a conspecific animal while being exposed to distressing stimuli. Although evidence indicates that the prelimbic cortex of the medial prefrontal cortex (mPFC PL) plays a prominent role in social buffering, its underlying synaptic mechanisms remain unclear. In this study, we observed synaptic activity changes in the mPFC PL using whole-cell patch-clamp recording and investigated the relationship between synaptic activity and social buffering under fear-exposed conditions. In the passive avoidance test, freezing behavior increased and black room preference decreased significantly in single-exposed rats, whereas both behaviors significantly returned to control levels in pair-exposed rats. Whole-cell patch-clamp recording showed a considerable reduction in the excitatory-inhibitory ratio (E/I ratio) in single-exposed rats due to a significant decrease in evoked EPSC (eEPSC), while evoked IPSC (eIPSC) remained unchanged. However, in the pair-exposed rats, the E/I ratio, eEPSC, and eIPSC showed partial recovery toward control levels, with the E/I ratio restored to control-like levels while eEPSC remained reduced. We also observed lower peak amplitude and delayed saturation in the input-output (I-O) curve of single-exposed rats compared to control and pair-exposed rats. These findings, consistently supported by multilevel analyses (cell, animal, and linear mixed-effects models with animal as a random factor), suggest that the E/I ratio of mPFC PL pyramidal neurons is associated with social buffering-mediated fear attenuation.