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

doi:10.1016/j.isci.2023.107878

The PrL^Glu→avBNST^GABA circuit rapidly modulates depression-like behaviors in male mice

iScience. 2023 Sep 12;26(10):107878. doi: 10.1016/j.isci.2023.107878. eCollection 2023 Oct 20.

Authors

Jie-Ying Chen^{1

2

3}, Ke Wu^{1

2

3}, Miao-Miao Guo^{1

2

3}, Wei Song^{1

2

3}, Si-Ting Huang^{1

2

3}, Yong-Mei Zhang^{1

2

3}

Affiliations

¹ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
² Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
³ NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221002, China.

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 PrL^Glu→avBNST^GABA circuit. Furthermore, the fast-acting effect of ketamine on depressive behaviors was diminished when the circuit was inhibited. To summarize, activating the PrL^Glu→avBNST^GABA circuit quickly ameliorated depression-like behaviors. Thus, we propose the PrL^Glu→avBNST^GABA circuit as a target for fast regulation of depression.

Keywords: Anesthesiology; Neuroscience.