Dorsal BNST DRD2+ neurons mediate sex-specific anxiety-like behavior induced by chronic social isolation

• Published in: Cell reports (Cambridge) 2023-07, Vol.42 (7), p.112799-112799, Article 112799
• Main Authors: Zheng, Chaowen, Wei, Lei, Liu, Boyi, Wang, Qingxiu, Huang, Yanwang, Wang, Shangyi, Li, Xiangning, Gong, Hui, Wang, Zuoren
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; chronic stress; CP: Neuroscience; dBNST; dopamine receptor; Female; Male; neural plasticity; Neurons; Rats; Receptors, Dopamine D2; Septal Nuclei - physiology; Social Isolation; Stress, Psychological
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112799

The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder. [Display omitted] •PWSI stress induces male-specific emotional and social dysfunction•Excitability of dBNST Drd2+, but not Drd1+, neurons of PWSI rats shows an increase•There is an enhancement of E:I balance of dBNST Drd2+ neurons in PWSI rats•Inhibition of dBNST Drd2+ neurons rescues anxiety-like phenotype caused by PWSI stress Zheng et al. find an important mechanism by which post-weaning social isolation stress induces male-specific anxiety-like behavior by the increase of the excitability of dBNST Drd2+, but not Drd1+, neurons and enhancement of E:I balance of dBNST Drd2+ neurons.