Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice

Ya-Wei Ji, Zi-Lin Shen, Xue Zhang, Kairan Zhang, Tao Jia, Xiangying Xu, Huizhen Geng, Yu Han, Cui Yin, Jian-Jun Yang, Jun-Li Cao (), Chunyi Zhou () and Cheng Xiao ()
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Ya-Wei Ji: Xuzhou Medical University
Zi-Lin Shen: Xuzhou Medical University
Xue Zhang: Xuzhou Medical University
Kairan Zhang: Xuzhou Medical University
Tao Jia: Xuzhou Medical University
Xiangying Xu: Xuzhou Medical University
Huizhen Geng: Xuzhou Medical University
Yu Han: Xuzhou Medical University
Cui Yin: Xuzhou Medical University
Jian-Jun Yang: The First Affiliated Hospital of Zhengzhou University
Jun-Li Cao: Xuzhou Medical University
Chunyi Zhou: Xuzhou Medical University
Cheng Xiao: Xuzhou Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: Abstract Nucleus- and cell-specific interrogation of individual basal forebrain (BF) cholinergic circuits is crucial for refining targets to treat comorbid chronic pain-like and depression-like behaviour. As the ventral pallidum (VP) in the BF regulates pain perception and emotions, we aim to address the role of VP-derived cholinergic circuits in hyperalgesia and depression-like behaviour in chronic pain mouse model. In male mice, VP cholinergic neurons innervate local non-cholinergic neurons and modulate downstream basolateral amygdala (BLA) neurons through nicotinic acetylcholine receptors. These cholinergic circuits are mobilized by pain-like stimuli and become hyperactive during persistent pain. Acute stimulation of VP cholinergic neurons and the VP-BLA cholinergic projection reduces pain threshold in naïve mice whereas inhibition of the circuits elevated pain threshold in pain-like states. Multi-day repetitive modulation of the VP-BLA cholinergic pathway regulates depression-like behaviour in persistent pain. Therefore, VP-derived cholinergic circuits are implicated in comorbid hyperalgesia and depression-like behaviour in chronic pain mouse model.

Date: 2023
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DOI: 10.1038/s41467-023-37968-x

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