Single-cell RNA sequencing uncovers the cell type-dependent transcriptomic changes in the retrosplenial cortex after peripheral nerve injury
Jing-Hua Wang,
Cheng Wu,
Yan-Na Lian,
Xiao-Wen Cao,
Zi-Yue Wang,
Jia-Jun Dong,
Qin Wu,
Li Liu,
Li Sun,
Wei Chen,
Wen-Juan Chen,
Zhi Zhang,
Min Zhuo,
Xiang-Yao Li
Affiliations
Jing-Hua Wang
Department of Psychiatry of the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Cheng Wu
Department of Psychiatry of the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China; Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9JU, UK
Yan-Na Lian
Department of Psychiatry of the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Xiao-Wen Cao
Department of Psychiatry of the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Zi-Yue Wang
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Jia-Jun Dong
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China
Qin Wu
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China
Li Liu
Core Facilities of the School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Li Sun
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
Wei Chen
Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China
Wen-Juan Chen
Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China
Zhi Zhang
Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China
Min Zhuo
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Xiang-Yao Li
Department of Psychiatry of the Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain, Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China; Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9JU, UK; Corresponding author
Summary: The retrosplenial cortex (RSC) is a vital area for storing remote memory and has recently been found to undergo broad changes after peripheral nerve injury. However, little is known about the role of RSC in pain regulation. Here, we examine the involvement of RSC in the pain of mice with nerve injury. Notably, reducing the activities of calcium-/calmodulin-dependent protein kinase type II-positive splenial neurons chemogenetically increases paw withdrawal threshold and extends thermal withdrawal latency in mice with nerve injury. The single-cell or single-nucleus RNA-sequencing results predict enhanced excitatory synaptic transmissions in RSC induced by nerve injury. Local infusion of 1-naphthyl acetyl spermine into RSC to decrease the excitatory synaptic transmissions relieves pain and induces conditioned place preference. Our data indicate that RSC is critical for regulating physiological and neuropathic pain. The cell type-dependent transcriptomic information would help understand the molecular basis of neuropathic pain.
