Medullary serotonin neurons and their roles in central respiratory chemoreception

Much progress has been made in our understanding of central chemoreception since the seminal experiments of Fencl, Loeschcke, Mitchell and others, including identification of new brainstem regions and specific neuron types that may serve as central “sensors” of CO2/pH. In this review, we discuss key attributes, or minimal requirements a neuron/cell must possess to be defined as a central respiratory chemoreceptor, and summarize how well each of the various candidates fulfill these minimal criteria—especially the presence of intrinsic chemosensitivity. We then discuss some of the in vitro and in vivo evidence in support of the conclusion that medullary serotonin (5-HT) neurons are central chemoreceptors. We also provide an additional hypothesis that chemosensitive medullary 5-HT neurons are poised to integrate multiple synaptic inputs from various other sources thought to influence ventilation. Finally, we discuss open questions and future studies that may aid in continuing our advances in understanding central chemoreception.