Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development. (6th March 2017)

• Record Type: Journal Article
• Authors: Cerpa, Veronica J.; Wu, Yuanming; Bravo, Eduardo; Teran, Frida A.; Flynn, Rachel S.; Richerson, George B.
• Is Part Of: Neuroscience. Volume 344(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-03-06
• Subjects: AHP afterhyperpolarization -- CI chemosensitivity index -- DIC differential interference contrast -- EYFP enhanced yellow fluorescent protein -- ƒR respiratory frequency -- HCVR hypercapnic ventilatory response -- RTN retrotrapezoid nucleus -- SIDS sudden infant death syndrome -- VE ventilation -- VO2 oxygen consumption -- VT tidal volume; serotonin -- chemoreception -- Lmx1b -- respiratory; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.09.002
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Early postnatal ages 5-HT neurons provide tonic drive to the respiratory network only. Early postnatal ages 5-HT neurons do not contribute to chemoreception. 5-HT neurons from P21 animals switch their role from tonic drive to chemoreceptors. Our results could be related to the ventilatory abnormalities proposed in SIDS. Abstract: Serotonin (5-HT) neurons contribute to respiratory chemoreception in adult mice, but it is unclear whether they play a similar role in neonatal mice. We studied breathing during development in Lmx1b f/f/p mice, which lack 5-HT neurons. From postnatal days 1–7 (P1–P7), ventilation of Lmx1b f/f/p mice breathing room air was 50% of WT mice ( p < 0.001). By P12, baseline ventilation increased to a level equal to WT mice. In contrast, the hypercapnic ventilatory response (HCVR) of neonatal Lmx1b f/f/p and WT mice was equal to each other, but were both much less than adult WT mice. By P21 the HCVR of WT mice increased to near adult levels, but the HCVR of Lmx1b f/f/p mice had not changed, and was 42% less than WT mice. Primary cell cultures were prepared from the ventromedial medulla of neonatal mice, and patch-clamp recordings were made from neurons identified as serotonergic by expression of a reporter gene. In parallel with developmental changes of the HCVR in vivo, 5-HT neurons had little chemosensitivity to acidosis until 12 days in vitro (DIV), after which their response increased to reach a plateau around 25 DIV. Neonatal Lmx1b f/f/p mice displayed high mortality and decreased growth rate, and this worsened in hypoxia. Mortality was decreased in hyperoxia. These results indicate that maturation of 5-HT neurons contributes to development of respiratory CO2 /pH chemoreception during the first few weeks of life in mice in vivo . A defect in the 5-HT system in early postnatal life decreases survival due in part to hypoxia.