2. Academic Validation
  3. Central amygdala-substantia nigra pars compacta circuit mediates anxiety- and depression-like behaviors in MPTP-treated mice

Central amygdala-substantia nigra pars compacta circuit mediates anxiety- and depression-like behaviors in MPTP-treated mice

  • Exp Neurol. 2025 Oct 1:395:115489. doi: 10.1016/j.expneurol.2025.115489.
Haixia Tang 1,  Yiheng Li 2,  Pengcheng Huang 3,  Haijie Xiang 4,  Xinyu Long 1,  Menghua Li 1,  Doudou Zhao 1,  Ziye Jia 1,  Kaiyan Jiang 1,  Qing Li 1,  Yuting He 1,  Li Ying 5,  Yuanjian Yang 2,  Wenquan Zou 6,  Ying Xiong 7,  Daojun Hong 8
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 2 Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330029, Jiangxi, China; Nanchang City Key Laboratory of Biological Psychiatry, Health Commission of Jiangxi Province Key Laboratory of Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang 330029, Jiangxi, China.
  • 3 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Rare Disease Center, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 4 Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang University, Nanchang, China.
  • 5 Institute of Neurosurgery, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China.
  • 6 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Departments of Pathology and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • 7 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Institute of Neurology, Jiangxi Academy of Clinical Medical Science, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.; Rare Disease Center, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Key Laboratory of Rare Neurological Diseases of Jiangxi Provincial Health Commission, Jiangxi Medical College, Nanchang University, Nanchang, China; Postdoctoral Research Station, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address: ndyfy10015@ncu.edu.cn.
  • 8 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Institute of Neurology, Jiangxi Academy of Clinical Medical Science, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.; Rare Disease Center, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Key Laboratory of Rare Neurological Diseases of Jiangxi Provincial Health Commission, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address: hdj@ncu.edu.cn.
PMID: 41043680 DOI: 10.1016/j.expneurol.2025.115489
Abstract

Parkinson's disease (PD) is characterized by progressive degeneration of substantia nigra pars compacta (SNc) dopamine (DA) neurons, leading to motor dysfunction. Non-motor symptoms of PD, such as neuropsychiatric symptoms (anxiety and depression), often precede motor symptoms and seriously affect quality of life, but the mediating mechanism has not been well understood. The SNc receives input from somatostatin (SOM) neurons in the central amygdala (CeA), which convey reward related information. This study demonstrated that optogenetic activation of CeASOM-SNc circuit induced real-time place preference (RTPP) and alleviated anxiety-like behaviors caused by acute stress. SOM neurons in the CeA preferentially targeted GABAergic neurons in the SNc, optogenetic activation of CeASOM-SNc may activate TH neurons in the SNc through disinhibition. The response of CeA neurons to reward was blunted in MPTP-treated mice, and chronic chemogenetic silencing of CeA-SNc induced anxiety- and depression-like behaviors in mice. Furthermore, chronically chemogenetic activation of CeASOM-SNc or DA neurons in SNc alleviated anxiety- and depression-like behaviors in MPTP-treated mice. Reward-based chocolate intervention alleviated depression-like behaviors of MPTP-treated mice. In summary, our results indicate that the CeASOM-SNc circuit may mediate anxiety- and depression-like behaviors by regulating the activity of SNc DA neurons.

Keywords

Central amygdala; Neuropsychiatric symptoms; Parkinsons disease; Somatostatin neurons; Substantia nigra pars compacta.

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