Intermittent hypoxia-induced respiratory long-term facilitation is dominated by enhanced burst frequency, not amplitude, in spontaneously breathing urethane-anesthetized neonatal rats

Acute intermittent hypoxia (AIH) triggers a form of respiratory plasticity known as long-term facilitation (LTF), which is manifested as a progressive increase in respiratory motor activity that lasts for minutes to hours after the hypoxic stimulus is removed. Respiratory LTF has been reported in numerous animal models, but it appears to be influenced by a variety of factors (e.g., species, age, and gender). While most studies focusing on respiratory LTF have been conducted in adult (including young adult) rat preparations, little is known about the influence of postnatal maturation on AIH-induced respiratory LTF. To begin to address this issue, we examined diaphragm EMG activity in response to and at 5-min intervals for 60 min following three 5-min episodes of hypoxia (8% O-2) in urethane-anesthetized spontaneously breathing P14-P15 neonatal rats (n = 15). For these experiments, the hypoxic episodes were separated by hyperoxia (40% O-2), and all rats were continuously supplied with similar to 4% CO2. During the AIH trials, burst frequency was increased by similar to 20-90% above baseline in each of the rats examined while changes in burst amplitude were highly variable. Following the AIH episodes, respiratory LTF was characterized by predominantly an increase in burst frequency (f(LTF)) ranging from similar to 10% to 55%, with most rats exhibiting a 20-40% increase. In seven rats, however, an increase in amplitude (amp(LTF)) (similar to 10%, n = 3; similar to 20%, n = 3; similar to 30%, n = 1) was also noted. These data suggest that in contrast to observations in anesthetized ventilated adult rats, in anesthetized spontaneously breathing P14-P15 neonatal rats, respiratory LTF is dominated by f(LTF), not amp(LTF).