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An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice

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 neura...

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Autores principales: Zhang, Ting-Ting, Guo, Su-Shan, Wang, Hui-Ying, Jing, Qi, Yi, Xin, Hu, Zi-Han, Yu, Xin-Ren, Xu, Tian-Le, Liu, Ming-Gang, Zhao, Xuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169993/
https://www.ncbi.nlm.nih.gov/pubmed/36528690
http://dx.doi.org/10.1007/s12264-022-00996-6
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author Zhang, Ting-Ting
Guo, Su-Shan
Wang, Hui-Ying
Jing, Qi
Yi, Xin
Hu, Zi-Han
Yu, Xin-Ren
Xu, Tian-Le
Liu, Ming-Gang
Zhao, Xuan
author_facet Zhang, Ting-Ting
Guo, Su-Shan
Wang, Hui-Ying
Jing, Qi
Yi, Xin
Hu, Zi-Han
Yu, Xin-Ren
Xu, Tian-Le
Liu, Ming-Gang
Zhao, Xuan
author_sort Zhang, Ting-Ting
collection PubMed
description 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.
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spelling pubmed-101699932023-05-11 An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice Zhang, Ting-Ting Guo, Su-Shan Wang, Hui-Ying Jing, Qi Yi, Xin Hu, Zi-Han Yu, Xin-Ren Xu, Tian-Le Liu, Ming-Gang Zhao, Xuan Neurosci Bull Original Article 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. Springer Nature Singapore 2022-12-17 /pmc/articles/PMC10169993/ /pubmed/36528690 http://dx.doi.org/10.1007/s12264-022-00996-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Zhang, Ting-Ting
Guo, Su-Shan
Wang, Hui-Ying
Jing, Qi
Yi, Xin
Hu, Zi-Han
Yu, Xin-Ren
Xu, Tian-Le
Liu, Ming-Gang
Zhao, Xuan
An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title_full An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title_fullStr An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title_full_unstemmed An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title_short An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice
title_sort anterior cingulate cortex-to-midbrain projection controls chronic itch in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169993/
https://www.ncbi.nlm.nih.gov/pubmed/36528690
http://dx.doi.org/10.1007/s12264-022-00996-6
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