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A ventral pallidum-locus coeruleus-lateral hypothalamus pathway modulates brain arousal in freely behaving and isoflurane-anesthetized male mice

Author

Listed:
  • Xiang-Ying Xu

    (School of Anesthesiology, Xuzhou Medical University
    Xuzhou Medical University
    School of Anesthesiology, Xuzhou Medical University)

  • Yue Xiao

    (School of Anesthesiology, Xuzhou Medical University
    Affiliated Hospital of Nantong University)

  • Xu Liu

    (School of Anesthesiology, Xuzhou Medical University)

  • Yue Huang

    (School of Anesthesiology, Xuzhou Medical University)

  • Ying Ji

    (School of Anesthesiology, Xuzhou Medical University)

  • Yawei Ji

    (School of Anesthesiology, Xuzhou Medical University)

  • Yuan Gao

    (School of Anesthesiology, Xuzhou Medical University)

  • Su Liu

    (Xuzhou Medical University
    School of Anesthesiology, Xuzhou Medical University
    Affiliated Hospital of Xuzhou Medical University)

  • Jian-Jun Yang

    (The First Affiliated Hospital of Nanjing Medical University)

  • Jun-Li Cao

    (School of Anesthesiology, Xuzhou Medical University
    Xuzhou Medical University
    School of Anesthesiology, Xuzhou Medical University
    Affiliated Hospital of Xuzhou Medical University)

  • Chunyi Zhou

    (School of Anesthesiology, Xuzhou Medical University
    Xuzhou Medical University
    School of Anesthesiology, Xuzhou Medical University)

  • Cheng Xiao

    (School of Anesthesiology, Xuzhou Medical University
    Xuzhou Medical University
    School of Anesthesiology, Xuzhou Medical University)

Abstract

Much progress has been made in the understanding of the neural circuits associated with sleep and anesthesia. As an important component among these circuits, the forebrain nuclei have been frequently interrogated. This study demonstrates that glutamatergic (Glu) neurons in the ventral pallidum (VP) enhance activity upon salient stimuli and state-dependently modulate brain arousal and motor activity in freely behaving male mice, and bidirectionally regulate the induction of and emergence from isoflurane general anesthesia. We delineate a neural pathway, consisting of VP Glu neurons→ noradrenergic (NA) neurons in the locus coeruleus (LC)→the lateral hypothalamus (LH) in male mice, controlling the release of noradrenaline in the LH and state-dependently modulated brain arousal, motor activity, and isoflurane general anesthesia through α2a receptors in the LH. Therefore, the VPGlu-LCNA-LH pathway and α2a receptors in the LH may be promising state-dependent regulators of brain arousal in both freely behaving and anesthetized states.

Suggested Citation

  • Xiang-Ying Xu & Yue Xiao & Xu Liu & Yue Huang & Ying Ji & Yawei Ji & Yuan Gao & Su Liu & Jian-Jun Yang & Jun-Li Cao & Chunyi Zhou & Cheng Xiao, 2025. "A ventral pallidum-locus coeruleus-lateral hypothalamus pathway modulates brain arousal in freely behaving and isoflurane-anesthetized male mice," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59857-1
    DOI: 10.1038/s41467-025-59857-1
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    References listed on IDEAS

    as
    1. Haiyan Sun & Zhilin Li & Zhentong Qiu & Yu Shen & Qingchen Guo & Su-Wan Hu & Hai-Lei Ding & Shuming An & Jun-Li Cao, 2023. "A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Tao Jia & Ying-Di Wang & Jing Chen & Xue Zhang & Jun-Li Cao & Cheng Xiao & Chunyi Zhou, 2022. "A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Lauren Faget & Vivien Zell & Elizabeth Souter & Adam McPherson & Reed Ressler & Navarre Gutierrez-Reed & Ji Hoon Yoo & Davide Dulcis & Thomas S. Hnasko, 2018. "Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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