5-HT Neurons and Central CO₂ Chemoreception

Many neurons within the medullary raphe project to nuclei that control respiratory motor output. Through release of serotonin (5-HT) and the co-localized neuropeptides substance P and thyrotropin-releasing hormone, these neurons provide an essential tonic drive that maintains 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 and returning CO₂ and pH back to normal. Some 5-HT neurons in the midbrain may play a similar role in sensing changes in blood CO₂and may induce arousal when CO₂ levels increase during sleep. Defects in 5-HT neurons occur in a variety of human diseases and may contribute to abnormalities of respiratory control and blood gas homeostasis.