CORTICOSTERONE RESTORES CALCIUM DYNAMICS AND PLASTICITY IN THE BASOLATERAL AMYGDALA FOLLOWING STRESS-INDUCED PTSD AND DEPRESSION-LIKE CHANGES

Post-trauma glucocorticoid therapy shows promise for preventing stress-related psychopathology, such as posttraumatic stress disorder (PTSD), yet its underlying circuit and molecular mechanisms remain poorly understood. Here, we tested whether a single dose of corticosterone administered shortly after a 2 hour immobilization traumatic stress prevents delayed behavioral alterations in mice by restoring synaptic and circuit modulations in the basolateral amygdala (BLA). Principal component analysis of multidimensional behavior confirmed that corticosterone rescued stress-induced anxiety-, depressive-like behavior, and social impairments. At the molecular level, corticosterone modulated the expression of Protein Phosphatase Mg2+/Mn2+ Dependent 1F (Ppm1f) shortly after stress, and the modulations were correlated with behavior, supporting its potential as a peripheral biomarker. At the synaptic level, stress induced sex-opposite effects in BLA plasticity: long-term potentiation was stronger in females but weaker in males, both of which were normalized by corticosterone. In vivo calcium imaging revealed that corticosterone treatment attenuated BLA neuronal activity in anxiogenic contexts and dampened novelty-specific responses, with stimulus and sex-specific modulations. Our findings demonstrate in a PTSD and depression-like model that the brain’s representation of a stimulus is flexible rather than fixed, with different neurons taking on this role under changing conditions, while sex and glucocorticoid treatment shape plasticity and calcium signaling in the BLA, guiding new strategies for preventing psychopathology.