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6d ago

Spinal Cholinergic Neurons Boost Breathing and Move Toward Therapeutic Testing

A Cell Reports study confirms that V0C cholinergic interneurons amplify phrenic motor output during CO2 challenges, leading researchers to initiate preclinical trials of targeted therapies in spinal cord injury plus neurodegenerative disease models

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The study showed that blocking signals from these spinal cord cells made it harder for the body to breathe properly when there was too much carbon dioxide (CO2) in the blood, a condition known as hypercapnia. Credit: Neuroscience News
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Overview

  • Researchers used monosynaptic mapping to identify genetically defined V0C cholinergic interneurons as the predominant spinal input to phrenic motor neurons that drive diaphragm contractions.
  • Electrophysiology, behavioral assays and microscopy in genetically modified mice showed these interneurons receive phasic excitation from brainstem centers and augment respiratory output via M2 muscarinic receptors under hypercapnia.
  • Selective silencing of V0C interneuron neurotransmission significantly impaired the adaptive breathing response to elevated CO₂, underscoring their critical role in respiratory control.
  • Published in August 2025 in Cell Reports, the findings build on over 30 years of motor-circuit research at Case Western Reserve and involve collaborators from St. Andrews, Calgary and the Biomedical Research Foundation Academy of Athens.
  • The research team has initiated next-stage preclinical testing to assess therapies targeting these interneurons for breathing restoration in spinal cord injury plus models of ALS and Alzheimer’s disease.