A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression
Xia Zhu,
Wenjie Zhou,
Yan Jin,
Haodi Tang,
Peng Cao,
Yu Mao,
Wen Xie,
Xulai Zhang,
Fei Zhao,
Min-Hua Luo,
Haitao Wang,
Jie Li,
Wenjuan Tao,
Zahra Farzinpour,
Likui Wang,
Xiangyao Li,
Juan Li,
Zheng-Quan Tang,
Chenghua Zhou,
Zhizhong Z. Pan,
Zhi Zhang
Affiliations
Xia Zhu
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Wenjie Zhou
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Yan Jin
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Haodi Tang
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Peng Cao
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Yu Mao
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China; Department of Anesthesiology and Department of Pain Management, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
Wen Xie
Department of Psychology, Anhui Mental Health Center, Hefei 230026, PR China
Xulai Zhang
Department of Psychology, Anhui Mental Health Center, Hefei 230026, PR China
Fei Zhao
State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China
Min-Hua Luo
State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China
Haitao Wang
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Jie Li
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Wenjuan Tao
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China; Department of Anesthesiology and Department of Pain Management, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
Zahra Farzinpour
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Likui Wang
Department of Anesthesiology and Department of Pain Management, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
Xiangyao Li
Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Key Laboratory of Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China
Juan Li
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China
Zheng-Quan Tang
Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Chenghua Zhou
Department of Anesthesiology and Pain Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Zhizhong Z. Pan
Department of Anesthesiology and Pain Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Zhi Zhang
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China; Corresponding author
Summary: While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamatergic neurons in the parafascicular nucleus (GluPF). These GluPF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABACeA→GluPF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABACeA→GluPF→S2 pathway in controlling at least some aspects of CP. : Zhu et al. identify that GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamate neurons in the parafascicular nucleus (GluPF) and uncover the role of this pathway in regulation of pain symptoms in depression via connecting with the second somatosensory cortex. Keywords: comorbid pain, central nucleus of the amygdala, parafascicular nucleus, second somatosensory cortex, neural circuits, optogenetics, chemogenetics, retrograde trans-monosynaptic tracing, GABA neurons, glutamate neurons
