Ventrolateral medullary neurons show age-dependent depolarizations to hypoxia in vitro

Central mechanisms are likely responsible for the larger respiratory activation in response to hypoxia in the adult compared to the neonatal animal. One possible site for this effect is in the ventrolateral medulla, an area known to be involved in the cardiorespiratory responses to hypoxia. Neurons in this area are stimulated by hypoxia both in vivo and in vitro. The purpose of the present study was to determine if changes in the magnitude of this excitatory response occur during early postnatal development. Whole-cell patch recordings were made from neurons in the ventrolateral medulla (VLM) in a 400-micrograms brain slice preparation. The basal properties and responses to a brief (90 s) hypoxic stimulus (5% CO2/95% N2) were compared between neurons from neonatal (P < 16) and juvenile (P16-38) rats. An excitation consisting of a depolarization, increase in spike frequency and decrease in input resistance was observed during hypoxia in eighty-three percent of juvenile but in only 58% of the neonatal VLM neurons. Moreover, the magnitude of this response was greater in the juvenile (8.2 +/- 1.3 mV) than in the neonatal (4.8 +/- 0.5 mV) neurons. A second type of depolarizing response, consisting of a more pronounced depolarization interrupted by a brief hyperpolarization that returned to a depolarized state and not associated with an increased discharge frequency, occurred in only 3% of the neurons from the juvenile animals compared to 18% of those from neonatal rats. The remaining proportion of the VLM neurons studied were hyperpolarized or were unaffected by hypoxia. Measurements of tissue pO2 indicate that none of the above differences are due to variations in the hypoxic stimulus between neonatal and adult slices. The results of this study suggest that the hypoxic-induced depolarizations observed in VLM neurons change during development. These developmental changes may contribute to the changes that occur in cardiorespiratory responses to acute systemic hypoxia during early development.