An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice.
10.1007/s12264-022-00996-6
- Author:
Ting-Ting ZHANG
1
;
Su-Shan GUO
2
;
Hui-Ying WANG
1
;
Qi JING
1
;
Xin YI
2
;
Zi-Han HU
1
;
Xin-Ren YU
1
;
Tian-Le XU
2
;
Ming-Gang LIU
3
;
Xuan ZHAO
4
Author Information
1. Department of Anesthesiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
2. Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
3. Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. lmg11302000@126.com.
4. Department of Anesthesiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. zhaoxuan1026@hotmail.com.
- Publication Type:Journal Article
- Keywords:
Anterior cingulate cortex;
Chemogenetics;
Chronic itch;
Neural circuit;
Ventral tegmental area
- MeSH:
Mice;
Animals;
Gyrus Cinguli/physiology*;
Pruritus/pathology*;
Mesencephalon;
Cerebral Cortex/pathology*;
Neurons/pathology*
- From:
Neuroscience Bulletin
2023;39(5):793-807
- CountryChina
- Language:English
-
Abstract:
Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
