Hyperexcitation of ovBNST CRF neurons during stress contributes to female-biased expression of anxiety-like avoidance behaviors

• DOI: 10.1126/sciadv.adk7636
• Publication Date: 2024-05-10T17:58:45Z
• Authors: Na Zhang; Sha Zhao; Yanqiao Ma; Zhixin Xiao; Bao Xue; Yuan Dong; Qingyu Wang; Huamin Xu; Xia Zhang; Ying Wang
• Keywords: Male; Neurons; 0301 basic medicine; Behavior, Animal; Corticotropin-Releasing Hormone; Anxiety; Receptors, Corticotropin-Releasing Hormone; Mice; 03 medical and health sciences; Avoidance Learning; Animals; Female; Septal Nuclei; Stress, Psychological; Neuroscience

Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies. Moreover, optogenetic modulation to exchange the activation pattern of ovBNST CRF neurons during stress between female and male mice could reverse their susceptibility to anxiety. Last, CRF receptor type 1 (CRFR1) mediated the CRF-induced excitation of ovBNST CRF neurons and showed female-biased expression. Specific knockdown of the CRFR1 level in ovBNST CRF neurons in female or overexpression that in male could reverse their susceptibility to anxiety. Therefore, we identify that CRFR1-mediated hyperexcitation of ovBNST CRF neurons in female mice encode the female-biased susceptibility to anxiety.