Learning to breathe: Habituation of Hering–Breuer inflation reflex emerges with postnatal brainstem maturation

•Postnatal maturation of the Hering–Breuer lung inflation reflex (HBR) was investigated in perfused brainstem preparations of rat.•Repetitive vagal stimulation triggered stereotyped prolongations of expiration throughout the experimental protocol in neonatal rats.•Contrary, juvenile rats showed progressive decrease in vagal or lung inflation evoked expiratory lengthening to a constant stimulus.•We conclude that HBR habituation emerges at late stages of respiratory network maturation.

The Hering–Breuer (HBR) reflex is considered a major regulatory feedback for the generation and patterning of respiratory activity. While HBR is important in neonates, its significance in adults is controversial. Previous experiments that investigated the plasticity of entrainment of the respiratory rhythm by vagal input demonstrated postnatal changes in HBR plasticity. Here we analyzed postnatal changes in the plasticity of HBR by mimicking the classic lung inflation tests with repetitive tonic vagal stimulation across different postnatal stages in an in situ perfused brainstem preparation of rat. The study shows that neonates stereotypically exhibit HBR stimulus-dependent prolongation of expiration while juvenile preparations (>postnatal day 16) showed significant habituation of HBR following repetitive stimulation. Subsequent experiments employing physiological lung inflation tests in situ confirmed HBR habituation in juveniles. We conclude that postnatal emergence of HBR habituation explains the weak contribution and high activation threshold of HBR in the regulation of eupnea.