Perinatal maturation of the mouse respiratory rhythm-generator: in vivo and in vitro studies.
In vivo (plethysmography) and in vitro (en bloc preparations) experiments were performed from embryonic day 16 (E16) to postnatal day 9 (P9) in order to analyse the perinatal maturation of the respiratory rhythm-generator in mice. At E16, delivered foetuses did not ventilate and survive but at E18 they breathed at about 110 cycles/min with respiratory cycles of variable individual duration. From E18 to P0-P2, the respiratory cycles stabilised without changes in the breathing parameters. However, these increased several-fold during the next days. Hypoxia increased breathing frequency from E18-P5 and only significantly affected ventilation from P3 onwards. At E16, in vitro medullary preparations (pons resection) produced rhythmic phrenic bursts at a low frequency (about 5 cycles/min) with variable cycle duration. At E18, their frequency doubled but cycle duration remained variable. After birth, the frequency did not change although cycle duration stabilised. At E18 and P0-P2, the in vitro frequency decreased by around 50% under hypoxia, increased by 40-50% under noradrenaline or substance P and was permanently depressed by the pontine A5 areas. At E16 however, hypoxia had no effects, both noradrenaline and substance P drastically increased the frequency and area A5 inhibition was not expressed at this time. At E18 and P0-P2, electrical stimulation and electrolytic lesion of the rostral ventrolateral medulla affected the in vitro rhythm but failed to induce convincing effects at E16. Thus, a major maturational step in respiratory rhythmogenesis occurs between E16-E18, in agreement with the concept of multiple rhythmogenic mechanisms.
Viemari
Jean-Charles
JC
Biology of Rhythm and Development, Groupe d'Etude des Réseaux Moteurs, FRE CNRS 2102, 280 Boulevard Sainte Marguerite, 13009 Marseille, France.
Burnet
Henri
H
Bévengut
Michelle
M
Hilaire
Gérard
G
D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation; D000860:Hypoxia; D008526:Medulla Oblongata / Q000254:growth & development* / Q000502:physiology*; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D010507:Periodicity; D010991:Plethysmography; D012119:Respiration; D013373:Substance P / Q000494:pharmacology / Q000502:physiology
D013373:Substance P; D009638:Norepinephrine