Chemogenetic stimulation of phrenic motor output and diaphragm activity

This study explores a new method to improve breathing by stimulating the nerves that control the diaphragm, the main muscle for breathing. The researchers used a technique called chemogenetics, which involves using special receptors that can be activated by specific drugs, to stimulate phrenic motor neurons. The study found that activating these receptors in the spinal cord increased the activity of the diaphragm and improved breathing in mice and rats. This approach may have potential for treating conditions where breathing is impaired, such as after a spinal cord injury. The researchers also found that targeting these receptors specifically to the phrenic motor neurons was more effective than non-specific expression in the mid-cervical spinal cord, suggesting that precise targeting is important for this approach.

• 1
  DREADD ligand JHU37160 (J60) caused a bilateral, sustained (>1 hour) increase in inspiratory EMG bursting in both wild-type and ChAT-Cre mice, with a greater relative increase in ChAT-Cre mice.
• 2
  In ChAT-Cre rats, intravenous J60 resulted in a sustained (>30 min) increase in tidal volume (VT) during spontaneous breathing, assessed using whole-body plethysmography without anesthesia.
• 3
  Phrenic nerve recordings in ChAT-Cre rats confirmed that J60 evoked a > 200% increase in inspiratory output under urethane anesthesia.