Magnitude And Mechanism of Phrenic Long-Term Facilitation Shift Between Daily Rest Vs Active Phase

Abstract Plasticity is a fundamental property of the neural system controlling breathing. One key example respiratory motor plasticity phrenic long-term facilitation (pLTF), persistent increase in nerve activity elicited by acute intermittent hypoxia (AIH). pLTF can arise from distinct cell signaling cascades initiated serotonin versus adenosine receptor activation, respectively; these interact via powerful cross-talk inhibition. Here, we demonstrate that daily rest active phase and duration hypoxic episodes within an AIH protocol have profound impact on magnitude even mechanism due to shifts serotonin/adenosine balance. Using historical “standard” (3, 5 min moderate episodes), unaffected exposure mid-active mid-rest phase, yet driving serotonin-dominant during adenosine-dominant phase. This mechanistic “flip” results combined influences hypoxia-evoked release normal cycles basal spinal between Since consisting shorter but same cumulative (15, 1 episodes) elicits less episodes, amplified diminished constraint serotonin-driven plasticity; other hand, this 15 × delivered suppresses elevated background levels low release. These findings importance balance regulating amplitude AIH-induced pLTF. emerging as promising therapeutic modality restore non-respiratory movements people with cord injury or ALS, knowledge how time-of-day episode has biological, experimental translational implications.