Stress-Responsive Neuronal Ensembles and β-Adrenergic Signaling in the Basolateral Amygdala Modulate the Infralimbic Cortical Activity and Govern the Delayed Stress-Induced Fear Extinction Deficit.

Stress is a critical risk factor for the development of psychological disorders, including anxiety and post-traumatic stress disorder. Key brain regions, including the basolateral amygdala (BLA) and the infralimbic medial prefrontal cortex (IL-mPFC), play crucial roles in fear regulation. Our previous research demonstrated that neuronal genomic activity of glucocorticoid receptors in the BLA during a 2†h acute restraint stress (ARS) is essential for inducing anxiety-like behavior 10†d later. Additionally, blocking BLA β-adrenergic signaling during the elevated plus maze is crucial for preventing this stress-induced delayed anxiety-like behavior. Here, we utilized adult male Wistar rats to expand on these findings, revealing that a single ARS session increases the activity of BLA neurons and their projections to the IL-mPFC while decreasing the activity of IL-mPFC neurons and their projections to the BLA during fear extinction. This finding highlights the key role of the BLA↔IL-mPFC circuitry in fear extinction and its susceptibility to acute stress-induced changes. Notably, the delayed stress-induced fear extinction deficit and decreased IL-mPFC activity during fear extinction depend on the stress-responsive BLA neuronal ensemble and BLA β-adrenergic signaling during contextual fear conditioning (CFC) 10†d poststress. Our findings demonstrate the significance of BLA β-adrenergic signaling during CFC, as it induces delayed stress-induced impairments in extinction and regulates IL-mPFC activity during fear extinction. Furthermore, this study indicates that the BLA is a pivotal regulator of delayed stress effects at both the circuitry and behavioral levels, thus shedding new light on the mechanisms underlying stress-related psychiatric conditions.