Brain adaptation to acute stress: effect of time, social buffering, and nicotinic cholinergic system

Both social behavior and stress responses rely on the activity of the prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) and on cholinergic transmission. We previously showed in adult C57BL/6J (B6) mice that social interaction has a buffering effect on stress-related prefrontal activity, depending on the β2-/- cholinergic nicotinic receptors (nAChRs, β2-/- mice). The latency for this buffer to emerge being short, we question here whether the associated brain plasticity, as reflected by regional c-fos protein quantification and PFC-BLA functional connectivity, is modulated by time. Overall, we show that time normalized the stress-induced PFC hyperactivation in B6 mice and PFC hypo-activation in β2-/- mice, with no effect on BLA. It also triggered a multitude of functional links between PFC subareas, and between PFC and BLA in B6 mice but not β2-/- mice, showing a central role of nAChRs in this plasticity. Coupled with social interaction and time, stress led to novel and drastic diminution of functional connectivity within the PFC in both genotypes. Thus, time, emotional state, and social behavior induced dissociated effects on PFC and BLA activity and important cortico-cortical reorganizations. Both activity and plasticity were under the control of the β2-nAChRs.