5-HT neurons and central CO2 chemoreception

Abstract Many neurons within the medullary raphe project to nuclei that control respiratory motor output. Through release of serotonin (5-HT) and the colocalized neuropeptides substance P (SP) and thyrotropin-releasing hormone these neurons provide tonic drive that helps maintain ventilation. Many 5-HT neurons are closely associated with large arteries of the brainstem, where they respond to changes in arterial CO2 levels by increasing their firing rate. These properties allow them to play an important role as central respiratory chemoreceptors, causing an increase in ventilation in response to increased CO2 levels so that CO2 and pH return back to normal. Some 5-HT neurons in the midbrain play a similar role in sensing changes in blood CO2, and induce arousal when CO2 levels increase during sleep. Defects in 5-HT neurons occur in a variety of human diseases and may play a critical role in the pathophysiology of sudden infant death syndrome (SIDS), sudden unexpected death in epilepsy (SUDEP) and panic disorder, each of which may involve abnormalities of respiratory control and blood gas homeostasis.