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Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling

Author

Listed:
  • Alexandria B. Marciante

    (University of Florida)

  • Arash Tadjalli

    (University of Florida
    3200 South University Drive)

  • Maria Nikodemova

    (University of Florida)

  • Kayla A. Burrowes

    (University of Florida)

  • Jose Oberto

    (University of Florida)

  • Edward K. Luca

    (University of Florida)

  • Yasin B. Seven

    (University of Florida)

  • Jyoti J. Watters

    (University of Florida
    2015 Linden Drive)

  • Tracy L. Baker

    (University of Florida
    2015 Linden Drive)

  • Gordon S. Mitchell

    (University of Florida)

Abstract

We report an important role for microglia in regulating neuroplasticity within phrenic motor neurons. Brief episodes of low oxygen (acute intermittent hypoxia; AIH) elicit a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF) that is regulated by the balance of competing serotonin vs adenosine-initiated cellular mechanisms. Serotonin arises from brainstem raphe neurons, but the source of adenosine is unknown. We tested if hypoxic episodes initiate phrenic motor neuron to microglia fractalkine signaling that evokes extracellular adenosine formation using a well-defined neurophysiology preparation in male rats. With moderate AIH, phrenic motor neuron adenosine 2A receptor activation undermines serotonin-dominant pLTF whereas severe AIH induces pLTF by the adenosine-dependent mechanism. Consequently, phrenic motor neuron fractalkine knockdown, microglial fractalkine receptor inhibition, and microglial ablation enhance moderate AIH, but suppress severe AIH-induced pLTF. We conclude, microglia play important roles in healthy spinal cords, regulating plasticity in motor neurons responsible for breathing.

Suggested Citation

  • Alexandria B. Marciante & Arash Tadjalli & Maria Nikodemova & Kayla A. Burrowes & Jose Oberto & Edward K. Luca & Yasin B. Seven & Jyoti J. Watters & Tracy L. Baker & Gordon S. Mitchell, 2024. "Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54619-x
    DOI: 10.1038/s41467-024-54619-x
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    References listed on IDEAS

    as
    1. Danyang Chen & Qianqian Lou & Xiang-Jie Song & Fang Kang & An Liu & Changjian Zheng & Yanhua Li & Di Wang & Sen Qun & Zhi Zhang & Peng Cao & Yan Jin, 2024. "Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Aarti Jagannath & Norbert Varga & Robert Dallmann & Gianpaolo Rando & Pauline Gosselin & Farid Ebrahimjee & Lewis Taylor & Dragos Mosneagu & Jakub Stefaniak & Steven Walsh & Teele Palumaa & Simona Pre, 2021. "Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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