Commentaries on Viewpoint: Central chemoreception is a complex system function that involves multiple brain stem sites

to the editor: Amniote vertebrates adjust the acid-base status of the blood through ventilatory alterations of PaCO2 and, to some degree, by renal modulation of bicarbonate concentration. Receptor systems for the ventilatory acid-base regulation has been studied mainly in mammals, in which the ventrolateral surface of the medulla oblongata that faces the cerebrospinal fluid of the forth ventricle has been historically taken as the primary receptor site. The earliest evidence for the existence of central chemoreceptor drive to breathing in vertebrates was obtained in 1958 by Loeschcke and colleagues (4) who perfused the fourth ventricle of cats with mock cerebrospinal fluid of different pH values and measured its effect on pulmonary ventilation. Fifty years latter, Nattie and Li (5) bring us to the frontiers of respiratory physiology related to central chemoreception and shows that it involves multiple sites within the hindbrain, and different neuronal types. According to this notion, 1) glutamatergic neurons in the retrotrapezoid nucleus (3), 2) serotoninergic neurons of the medullary raphe (2), and 3) noradrenergic neurons of the locus ceruleus (1) have all been proposed as putative central chemoreceptors. The authors hypothesize that these multiple receptor sites involved in central chemoreception provide stability in a closed-loop control system. The progress related to our knowledge of this area has amazingly increased over the last 50 years but it is even more amazing how little we currently know. Further research remains urgent.