The PrLGlu→avBNSTGABA circuit rapidly modulates depression-like behaviors in male mice
Jie-ying Chen,
Ke Wu,
Miao-miao Guo,
Wei Song,
Si-ting Huang,
Yong-mei Zhang
Affiliations
Jie-ying Chen
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China
Ke Wu
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China
Miao-miao Guo
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China
Wei Song
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China
Si-ting Huang
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China
Yong-mei Zhang
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China; Corresponding author
Summary: 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.
