Abstract
Depression is a global disease with a high prevalence. Here, we examine the role of the circuit from prelimbic mPFC (PrL) to the anterior ventral bed nucleus of the stria terminalis (avBNST) in depression-like mice through behavioral tests, immunofluorescence, chemogenetics, optogenetics, pharmacology, and fiber photometry. Mice exposed to chronic restraint stress with individual housing displayed depression-like behaviors. Optogenetic or chemogenetic activation of the avBNST-projecting glutamatergic neurons in the PrL had an antidepressant effect. Moreover, we found that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptors (AMPARs) play a dominant role in this circuit. Systemic administration of ketamine profoundly alleviated depression-like behaviors in the mice and rapidly rescued the decreased activity in the PrLGlu→avBNSTGABA circuit. Furthermore, the fast-acting effect of ketamine on depressive behaviors was diminished when the circuit was inhibited. To summarize, activating the PrLGlu→avBNSTGABA circuit quickly ameliorated depression-like behaviors. Thus, we propose the PrLGlu→avBNSTGABA circuit as a target for fast regulation of depression.