Inhibition of glutamatergic neurons in the dorsomedial periaqueductal gray alleviates excessive defensive behaviors of mice with post-traumatic stress disorder
10.12122/j.issn.1673-4254.2024.03.02
- VernacularTitle:抑制dmPAG区谷氨酸能神经元可减轻创伤后应激障碍小鼠的过度防御反应
- Author:
Yanxiang LI
1
,
2
;
Yongxin GUO
;
Fuyang CAO
;
Shuting GUO
;
Dinghao XUE
;
Zhikang ZHOU
;
Xinyu HAO
;
Li TONG
;
Qiang FU
Author Information
1. 解放军总医院第一医学中心麻醉科,北京 100853
2. 解放军陆军第七十一集团军医院麻醉科,江苏 徐州 221004
- Keywords:
dorsomedial periaqueductal grey;
post-traumatic stress disorder;
glutamatergic neurons;
defensive behavior;
midbrain neural circuits
- From:
Journal of Southern Medical University
2024;44(3):420-427
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.
