Serotonin neurons and central respiratory chemoreception: where are we now?

Serotonin (5-hydroxytryptamine, 5-HT) neurons are widely considered to play an important role in central respiratory chemoreception. Although many studies in the past decades have supported this hypothesis, there had been concerns about its validity until recently. One recurring claim had been that 5-HT neurons are not consistently sensitive to hypercapnia in vivo. Another belief was that 5-HT neurons do not stimulate breathing; instead, they inhibit or modulate respiratory output. It was also believed by some that 5-HT neuron chemosensitivity is dependent on TASK channels, but mice with genetic deletion of TASK-1 and TASK-3 have a normal hypercapnic ventilatory response. This review explains why these principal arguments against the hypothesis are not supported by existing data. Despite repeated challenges, a large body of evidence now supports the conclusion that at least a subset of 5-HT neurons are central chemoreceptors.