부산대학교 도서관

Stress produces differential behavioral responses through select molecular modifications to specific neurocircuitry elements. The orexin (Orx) system targets key components of this neurocircuitry in the basolateral amygdala (BLA). We assessed the contribution of intra-BLA Orx 1 receptors (Orx 1 Rs) in the expression of stress-induced phenotypes of mice. Using the Stress Alternatives Model, a social stress paradigm that produces two behavioral phenotypes, we characterized the role of intra-BLA Orx 1 R using acute pharmacological inhibition (SB-674042) and genetic knockdown (AAV-U6-Orx 1 R-shRNA) strategies. In the BLA, we observed that Orx 1 R (H crtr 1) messenger RNA is predominantly expressed in CamKIIα+ glutamatergic neurons and rarely in GABAergic (gamma-aminobutyric acidergic) cells. While there is a slight overlap in H crtr 1 and Orx 2 receptor (H crtr 2) messenger RNA expression in the BLA, we find that these receptors are most often expressed in separate cells. Antagonism of intra-BLA Orx 1 R after phenotype formation shifted behavioral expression from stress-sensitive (Stay) to stress-resilient (Escape) responses, an effect that was mimicked by genetic knockdown. Acute inhibition of Orx 1 R in the BLA also reduced contextual and cued fear freezing responses in Stay animals. This phenotype-specific behavioral change was accompanied by biased molecular transcription favoring H crtr 2 over H crtr 1 and M apk 3 over P lcb 1 cell signaling cascades and enhanced B dnf messenger RNA. Functional reorganization of intra-BLA gene expression is produced by antagonism of Orx 1 R, which promotes elevated H crtr 2 , greater M apk 3 , and increased B dnf expression. Together, these results provide evidence for a receptor-driven mechanism that balances pro- and antistress responses within the BLA. [ABSTRACT FROM AUTHOR]