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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling

Alexandria B Marciante1, Arash Tadjalli1,2, Maria Nikodemova1

  • 1Breathing Research and Therapeutics Center, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL, USA.

Nature Communications
|November 28, 2024
PubMed

Insights

Microglia regulate breathing plasticity in motor neurons. Acute intermittent hypoxia (AIH) triggers signaling pathways involving fractalkines and adenosine, influencing phrenic long-term facilitation (pLTF) based on hypoxia severity.

Area of Science:

  • Neuroscience
  • Respiratory Physiology
  • Cellular Biology

Background:

  • Phrenic long-term facilitation (pLTF) is a form of respiratory motor plasticity.
  • pLTF is regulated by serotonin and adenosine signaling.
  • The source of adenosine in pLTF is currently unknown.

Purpose of the Study:

  • Investigate the role of microglia in neuroplasticity of phrenic motor neurons.
  • Determine if acute intermittent hypoxia (AIH) initiates fractalkine signaling between phrenic motor neurons and microglia.
  • Elucidate the mechanism of extracellular adenosine formation and its impact on pLTF.

Main Methods:

  • Utilized a neurophysiology preparation in male rats.
  • Manipulated fractalkine signaling (knockdown and receptor inhibition).
  • Employed microglial ablation and assessed pLTF under varying AIH severities.

Main Results:

  • Moderate AIH: Adenosine 2A receptor activation by phrenic motor neurons inhibits serotonin-dominant pLTF.
  • Severe AIH: Adenosine-dependent mechanisms induce pLTF.
  • Modulating microglial fractalkine signaling altered pLTF in an AIH severity-dependent manner.

Conclusions:

  • Microglia play a significant role in regulating neuroplasticity within phrenic motor neurons.
  • Microglial fractalkine signaling contributes to adenosine production, influencing respiratory motor plasticity.
  • The balance of microglial activity is critical for adapting breathing responses to hypoxia.

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