Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit

Area of Science:

• Neuroscience
• Respiratory Physiology
• Spinal Cord Injury Research

Background:

• Respiratory failure is a major complication of cervical spinal cord injury (SCI).
• Limited spontaneous respiratory recovery occurs after SCI, but the underlying mechanisms remain unclear.
• Understanding phrenic network neuroplasticity is crucial for improving SCI outcomes.

Purpose of the Study:

• To investigate structural plasticity in the left and right phrenic networks after C2 hemisection (C2Hx) in mice.
• To analyze changes in perineuronal nets (PNNs) and their association with neuroplasticity following unilateral cervical SCI.
• To elucidate the neuroanatomical adaptations of the phrenic motor system to respiratory trauma.

Main Methods:

• Utilized a pseudorabies virus, a trans-synaptic retrograde tracer, applied to the diaphragm muscle to label the entire phrenic motor network.
• Analyzed perineuronal net (PNN) distribution and glutamatergic synapses around phrenic motoneurons (PhMNs) and spinal interneurons in naïve and C2Hx mice.
• Compared structural plasticity between the left and right phrenic networks following right C2 hemisection.

Main Results:

• In naïve mice, PNNs were primarily located around phrenic motoneurons (PhMNs) in the ventral horn, not spinal interneurons.
• Right C2 hemisection led to a significant increase in PNNs and glutamatergic synapses around ipsilateral PhMNs.
• No significant changes in PNNs were observed in the left phrenic network after right C2Hx, revealing functional asymmetries.

Conclusions:

• The study reveals significant structural and functional asymmetries between the left and right phrenic networks.
• Increased PNNs and synapses after right C2Hx suggest greater neuroplasticity is required to compensate for respiratory dysfunction.
• Understanding these adaptive mechanisms is vital for developing targeted therapies to enhance respiratory recovery after SCI.