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Role of serotonergic dorsal raphe neurons in hypercapnia-induced arousals

Author

Listed:
  • Satvinder Kaur

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Roberto Luca

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Mudasir A. Khanday

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Sathyajit S. Bandaru

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Renner C. Thomas

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Rebecca Y. Broadhurst

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Anne Venner

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • William D. Todd

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Patrick M. Fuller

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Elda Arrigoni

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Clifford B. Saper

    (Beth Israel Deaconess Medical Center and Harvard Medical School)

Abstract

During obstructive sleep apnea, elevation of CO2 during apneas contributes to awakening and restoring airway patency. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) containing calcitonin gene related peptide (PBelCGRP neurons) are critical for causing arousal during hypercapnia. However, others found that genetic deletion of serotonin (5HT) neurons in the brainstem also prevented arousal from hypercapnia. To examine interactions between the two systems, we showed that dorsal raphe (DR) 5HT neurons selectively targeted the PBel. Either genetically directed deletion or acute optogenetic silencing of DRSert neurons dramatically increased the latency of mice to arouse during hypercapnia, as did silencing DRSert terminals in the PBel. This effect was mediated by 5HT2a receptors which are expressed by PBelCGRP neurons. Our results indicate that the serotonergic input from the DR to the PBel via 5HT2a receptors is critical for modulating the sensitivity of the PBelCGRP neurons that cause arousal to rising levels of blood CO2.

Suggested Citation

  • Satvinder Kaur & Roberto Luca & Mudasir A. Khanday & Sathyajit S. Bandaru & Renner C. Thomas & Rebecca Y. Broadhurst & Anne Venner & William D. Todd & Patrick M. Fuller & Elda Arrigoni & Clifford B. S, 2020. "Role of serotonergic dorsal raphe neurons in hypercapnia-induced arousals," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16518-9
    DOI: 10.1038/s41467-020-16518-9
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    Cited by:

    1. Stefano Nardone & Roberto Luca & Antonino Zito & Nataliya Klymko & Dimitris Nicoloutsopoulos & Oren Amsalem & Cory Brannigan & Jon M. Resch & Christopher L. Jacobs & Deepti Pant & Molly Veregge & Hari, 2024. "A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Satvinder Kaur & Nicole Lynch & Yaniv Sela & Janayna D. Lima & Renner C. Thomas & Sathyajit S. Bandaru & Clifford B. Saper, 2024. "Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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