Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors

After a spinal cord injury, the loss of serotonin from the brainstem leads to muscle paralysis. Over time, however, the spinal motoneurons adapt by expressing spontaneously active 5-HT2C receptors. These receptors restore calcium currents in the motoneurons, which allows them to regain their ability to produce muscle contractions, aiding in the recovery of motor functions like locomotion. However, these unregulated contractions can lead to muscle spasms. Blocking these spontaneously active receptors can reduce these spasms, suggesting a new approach for antispastic drug therapy.

• 1
  Changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active without 5-HT.
• 2
  Constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT, which helps motoneurons recover their ability to produce sustained muscle contractions and enables recovery of motor functions such as locomotion.
• 3
  Blocking constitutively active 5-HT2C receptors largely eliminates calcium currents and muscle spasms in both rats and humans, providing a new rationale for antispastic drug therapy.