Respiratory control by ventral surface chemoreceptor neurons in rats

A long-standing theory posits that central chemoreception, the CNS mechanism for CO2 detection and regulation of breathing, involves neurons located at the ventral surface of the medulla oblongata (VMS). Using in vivo and in vitro electrophysiological recordings, we identify VMS neurons within the rat retrotrapezoid nucleus (RTN) that have characteristics befitting these elusive chemoreceptors. These glutamatergic neurons are vigorously activated by CO2 in vivo, whereas serotonergic neurons are not. Their CO2 sensitivity is unaffected by pharmacological blockade of the respiratory pattern generator and persists without carotid body input. RTN CO2-sensitive neurons have extensive dendrites along the VMS and they innervate key pontomedullary respiratory centers. In brainstem slices, a subset of RTN neurons with markedly similar morphology is robustly activated by acidification and CO2. Their pH sensitivity is intrinsic and involves a background K+ current. In short, the CO2-sensitive neurons of the RTN are good candidates for the long sought-after VMS chemoreceptors.