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Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses

Author

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  • Patricia Bonnavion

    (Stanford University, 1201 Welch Road, Stanford, California 94305, USA
    Laboratory of Neurophysiology, Université Libre de Bruxelles (ULB)-UNI)

  • Alexander C. Jackson

    (University of California
    University of Connecticut)

  • Matthew E. Carter

    (Williams College)

  • Luis de Lecea

    (Stanford University, 1201 Welch Road, Stanford, California 94305, USA)

Abstract

The hypothalamic–pituitary–adrenal (HPA) axis functions to coordinate behavioural and physiological responses to stress in a manner that depends on the behavioural state of the organism. However, the mechanisms through which arousal and metabolic states influence the HPA axis are poorly understood. Here using optogenetic approaches in mice, we show that neurons that produce hypocretin (Hcrt)/orexin in the lateral hypothalamic area (LHA) regulate corticosterone release and a variety of behaviours and physiological hallmarks of the stress response. Interestingly, we found that Hcrt neuronal activity and Hcrt-mediated stress responses were inhibited by the satiety hormone leptin, which acts, in part, through a network of leptin-sensitive neurons in the LHA. These data demonstrate how peripheral metabolic signals interact with hypothalamic neurons to coordinate stress and arousal and suggest one mechanism through which hyperarousal or altered metabolic states may be linked with abnormal stress responses.

Suggested Citation

  • Patricia Bonnavion & Alexander C. Jackson & Matthew E. Carter & Luis de Lecea, 2015. "Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7266
    DOI: 10.1038/ncomms7266
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    Cited by:

    1. In-Jee You & Yeeun Bae & Alec R. Beck & Sora Shin, 2023. "Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Yan Zhang & Jiayi Shen & Famin Xie & Zhiwei Liu & Fangfang Yin & Mingxiu Cheng & Liang Wang & Meiting Cai & Herbert Herzog & Ping Wu & Zhi Zhang & Cheng Zhan & Tiemin Liu, 2024. "Feedforward inhibition of stress by brainstem neuropeptide Y neurons," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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