Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Although AIH consisting of moderate versus severe hypoxic episodes both elicit pLTF, they do so via completely distinct cellular mechanisms. In young adult male rats, moderate AIH (mAIH) elicits pLTF via a serotonin-driven, adenosine-constrained mechanism. In aged rats, mAIH-induced pLTF is diminished due to increased basal spinal adenosine levels that further constrain serotonin-driven pLTF. In contrast, in young male rats, severe AIH (sAIH) elicits pLTF via an adenosine-dominant, serotonin-constrained mechanism. Since basal spinal adenosine levels are elevated in aged male rats, we tested the hypothesis that adenosine-dependent, sAIH-induced pLTF is enhanced in aged versus young male rats. Young (~3 month) and aged (~20 month) male Sprague Dawley rats were urethane-anesthetized, ventilated, vagotomized, paralyzed, and exposed to sAIH (3, 5-min episodes, arterial PO2 = 25-30 mmHg; 5-min intervals). Integrated phrenic nerve activity was measured before (baseline), during each hypoxic episode, and for 60 minutes post-sAIH. Neither baseline phrenic burst amplitude, the short-term hypoxic phrenic response nor pLTF (% change from baseline in phrenic burst amplitude) were different in aged vs young male rats (132 ± 19% vs. 99 ± 17%, respectively). Thus, although sAIH-induced pLTF is not significantly elevated in aged versus young male rats as predicted, the capacity for adenosine-driven plasticity is preserved, in contrast with serotonin-dependent, mAIH-induced pLTF.
Burrowes et al. (Mon,) studied this question.