Conditional RAC1 knockout in motor neurons restores H‑reflex rate‑dependent depression after spinal cord injury

Spinal cord injury (SCI) often leads to spasticity, which involves increased excitability in the spinal H-reflex pathway. The study investigates a potential treatment by knocking out Rac1 protein in motor neurons after SCI. The researchers used a viral system to deliver Cre recombinase to motor neurons in mice with SCI, effectively knocking out Rac1. This knockout resulted in restoration of rate-dependent depression (RDD) and reduced H-reflex excitability, indicating a reversal of spasticity. The study also found that Rac1 knockdown reduced abnormal dendritic spine formation on motor neurons. These structural changes are associated with hyperexcitability, and disrupting Rac1 appears to mitigate these changes.

• 1
  Viral-mediated Rac1 knockdown in motor neurons after SCI significantly restored rate-dependent depression (RDD) of the H-reflex, indicating reduced hyperreflexia.
• 2
  Rac1 knockout reduced dendritic spine dysgenesis on motor neurons, specifically decreasing the presence of mature, mushroom-shaped spines and overall spine length and head size.
• 3
  Conditional Rac1 knockout did not impair gross locomotor recovery following mild SCI, suggesting that the treatment specifically targets spasticity without affecting overall motor function.