Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signal-ing to hypothalamus and habenula
10.3867/j.issn.1000-3002.2023.07.168
- Author:
Muran WANG
1
;
Peijun LI
;
Zewen LI
;
SILVA S.da BEATRIZ
;
Wu ZHENG
;
Zhenghua XIANG
;
Yan HE
;
Tao XU
;
CORDEIRO CRISTINA
;
Lu DENG
;
Yuwei DAI
;
Mengqian YE
;
Zhiqing LIN
;
Jianhong ZHOU
;
Xuzhao ZHOU
;
Fenfen YE
;
CUNHA A RODRIGO
;
Jiangfan CHEN
;
Wei GUO
Author Information
1. Wenzhou Medical University,Wenzhou 325000,China
- Keywords:
adenosine A2A receptors;
depression;
lateral septum
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):547-548
- CountryChina
- Language:Chinese
-
Abstract:
Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.
