The RTN/pFRG neurons are severely depleted in transgenic mouse model of the Central Congenital Hypoventilation Syndrome, a rare disease defined by the lack of CO2/pH responsiveness and RRG automaticity NVP-BEZ235 915019-65-7 during sleep. Although the RTN/pFRG neurons have a crucial role in ventilatory responses to CO2/pH changes in neonates, the serotonin neurons also contribute to the maintenance of blood gas homeostasis. As recently reviewed, the 5-HT neurons are involved in respiratory function and dysfunction, they synaptically contact the RRG, modulate the activity of the maturing RRG, are intrinsically chemosensitive in vitro, are stimulated by hypercapnia in vivo, and their disruption alters the ventilatory response to CO2/pH changes. In a transgenic mouse model of Prader-Willi syndrome, a rare disease with complex symptoms including frequent apnoeas during sleep and blunted ventilatory responses to CO2/pH, the medullary 5-HT levels are abnormally increased at birth and the ventilatory responses to CO2/ pH reduced. In addition, an altered 5HT system and insufficient ventilatoryresponses to CO2/pH and/or hypoxia during sleep might contribute to sudden infant death syndrome, the main cause of death in infants in industrialized countries. In medullary preparations of neonatal mice, acidosis increases the PBf by about 40% without affecting the phrenic burst amplitude, in agreement with previous reports in neonatal rats and foetal mice. Compelling evidence exist that the neonatal RTN/pFRG plays a main role in the PBf response to acidosis. However, the one min latency of the PBf response appears to be long since the RTN/pFRG chemoreceptors are close to the ventral surface and rapidly detect CO2/pH changes. The RRG responds in a few seconds when the RTN/pFRG neurons are stimulated by direct photo-activation in vivo or direct CO2/pH stimulation in vitro. The kinetics of the PBf responses to acidified aCSF applications have not been previously documented in details but latencies in a min range are commonly illustrated. Aside the superficial RTN/ pFRG chemoreceptors, several groups of chemoreceptors are described in discrete brainstem areas, such as the pontine catecholaminergic A5 and A6 areas, the ventrolateral medulla and the raphe areas. Indeed, the 5-HT neurons play a crucial role in respiratory function and dysfunction : they are intrinsically chemosensitive, synaptically contact the respiratory neurons and exert a facilitatory modulation on the RRG via a release of endogenous 5HT and activation of 5-HT1A receptors. Although some 5-HT neurons are very close to the ventral surface of the medulla, most are located deeper in the brainstem than the superficial RTN/pFRG chemoreceptors and may require a longer latency to detect acidosis.