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Orexin neurons inhibit sleep to promote arousal

Author

Listed:
  • Roberto Luca

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Stefano Nardone

    (Diabetes and Metabolism. Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Kevin P. Grace

    (Beth Israel Deaconess Medical Center and Harvard Medical School
    University of California Davis School of Medicine)

  • Anne Venner

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Michela Cristofolini

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Sathyajit S. Bandaru

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Lauren T. Sohn

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Dong Kong

    (F.M. Kirby Neurobiology Center. Children’s Hospital and Harvard Medical School)

  • Takatoshi Mochizuki

    (Graduate School of Science and Engineering. University of Toyama)

  • Bianca Viberti

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Lin Zhu

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Antonino Zito

    (Massachusetts General Hospital
    Harvard Medical School)

  • Thomas E. Scammell

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Clifford B. Saper

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Bradford B. Lowell

    (Diabetes and Metabolism. Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Patrick M. Fuller

    (Beth Israel Deaconess Medical Center and Harvard Medical School
    University of California Davis School of Medicine)

  • Elda Arrigoni

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

Abstract

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

Suggested Citation

  • Roberto Luca & Stefano Nardone & Kevin P. Grace & Anne Venner & Michela Cristofolini & Sathyajit S. Bandaru & Lauren T. Sohn & Dong Kong & Takatoshi Mochizuki & Bianca Viberti & Lin Zhu & Antonino Zit, 2022. "Orexin neurons inhibit sleep to promote arousal," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31591-y
    DOI: 10.1038/s41467-022-31591-y
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    References listed on IDEAS

    as
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    5. Daniel Kroeger & Gianna Absi & Celia Gagliardi & Sathyajit S. Bandaru & Joseph C. Madara & Loris L. Ferrari & Elda Arrigoni & Heike Münzberg & Thomas E. Scammell & Clifford B. Saper & Ramalingam Vetri, 2018. "Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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