Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development.
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 Lmx1bf/f/p mice, which lack 5-HT neurons. From postnatal days 1-7 (P1-P7), ventilation of Lmx1bf/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 Lmx1bf/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 Lmx1bf/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 12days in vitro (DIV), after which their response increased to reach a plateau around 25 DIV. Neonatal Lmx1bf/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.
['Cerpa|Veronica J|VJ|', 'Wu|Yuanming|Y|', 'Bravo|Eduardo|E|', 'Teran|Frida A|FA|', 'Flynn|Rachel S|RS|', 'Richerson|George B|GB|']
D000138:Acidosis D000200:Action Potentials D000818:Animals D000831:Animals, Newborn D002245:Carbon Dioxide D002478:Cells, Cultured D002628:Chemoreceptor Cells D000860:Hypoxia D060850:LIM-Homeodomain Proteins D008526:Medulla Oblongata D008822:Mice, Transgenic D018408:Patch-Clamp Techniques D010993:Plethysmography, Whole Body D012119:Respiration D059326:Serotonergic Neurons D012701:Serotonin D014157:Transcription Factors
respiratory chemoreception serotonin Lmx1b