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Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia

Author

Listed:
  • Satvinder Kaur

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Nicole Lynch

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Yaniv Sela

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Janayna D. Lima

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Renner C. Thomas

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Sathyajit S. Bandaru

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Clifford B. Saper

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

Abstract

About half of the neurons in the parabrachial nucleus (PB) that are activated by CO2 are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO2-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBclFoxP2 neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO2 during NREM sleep. Photo-activation of the PBclFoxP2 neurons increases respiration, whereas either photo-inhibition of PBclFoxP2 or genetic deletion of PB/KFFoxP2 neurons reduces the respiratory response to CO2 stimulation without preventing awakening. Thus, augmenting the PBcl/KFFoxP2 response to CO2 in patients with sleep apnea in combination with inhibition of the PBelCGRP neurons may avoid hypoventilation and minimize EEG arousals.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48773-5
    DOI: 10.1038/s41467-024-48773-5
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    References listed on IDEAS

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    1. 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.
    2. Carlos A. Campos & Anna J. Bowen & Carolyn W. Roman & Richard D. Palmiter, 2018. "Encoding of danger by parabrachial CGRP neurons," Nature, Nature, vol. 555(7698), pages 617-622, March.
    3. Dong-Yoon Kim & Gyuryang Heo & Minyoo Kim & Hyunseo Kim & Ju Ae Jin & Hyun-Kyung Kim & Sieun Jung & Myungmo An & Benjamin H. Ahn & Jong Hwi Park & Han-Eol Park & Myungsun Lee & Jung Weon Lee & Gary J., 2020. "A neural circuit mechanism for mechanosensory feedback control of ingestion," Nature, Nature, vol. 580(7803), pages 376-380, April.
    4. Joseph W. Arthurs & Anna J. Bowen & Richard D. Palmiter & Nathan A. Baertsch, 2023. "Parabrachial tachykinin1-expressing neurons involved in state-dependent breathing control," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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