Respiratory neuroplasticity: Mechanisms and translational implications of phrenic motor plasticity

Mitchell, Gordon S.; Baker, Tracy L.

doi:10.1016/b978-0-323-91534-2.00016-3

Cited by 23 publications

(37 citation statements)

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“…One important model of respiratory motor plasticity, known as phrenic long-term facilitation (pLTF), is elicited by repeated exposure to brief episodes of low oxygen, or acute intermittent hypoxia (AIH). pLTF is expressed as a persistent increase in phrenic nerve activity lasting hours after AIH has ended 2 . AIH also elicits plasticity in other respiratory ( e.g .…”

Section: Introductionmentioning

confidence: 99%

“…inspiratory intercostal, hypoglossal & laryngeal) and non-respiratory motor systems ( e.g . hand/arm and leg/walking function) 2,3 . Beyond it’s physiological relevance, repetitive AIH exposure is emerging as a promising therapeutic modality to improve breathing, walking and arm/hand function in people with chronic spinal cord injury 1,4,5 and ALS 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, when AIH consists of severe hypoxic episodes, pLTF arises from a distinct mechanism that requires cervical spinal adenosine 2A (A 2A ) receptor activation 16,17 . 5-HT 2 (G q -coupled) versus A 2A (G s -coupled) metabotropic receptors initiate completely distinct intra-cellular signaling cascades, known as the Q and the S pathways to phrenic motor facilitation, respectively 2,18,19 ( Figure 1 ). The Q and S pathways interact via powerful crosstalk inhibition: when both are equally activated, plasticity is cancelled 2,20 .…”

Section: Introductionmentioning

confidence: 99%

“…5-HT 2 (G q -coupled) versus A 2A (G s -coupled) metabotropic receptors initiate completely distinct intra-cellular signaling cascades, known as the Q and the S pathways to phrenic motor facilitation, respectively 2,18,19 ( Figure 1 ). The Q and S pathways interact via powerful crosstalk inhibition: when both are equally activated, plasticity is cancelled 2,20 . Thus, AIH-induced pLTF is not observed when the serotonin and adenosine-dependent mechanisms are activated concurrently by: 1) hypoxic episodes of intermediate severity 21 ; or 2) sustained moderate hypoxia 22 .…”

Section: Introductionmentioning

confidence: 99%

“…One factor known to impact basal adenosine levels in the CNS is time-of-day, particularly when comparing active versus resting phases 24–26 . Since studies on spinal respiratory motor plasticity have invariably been performed during the day, which is the rest phase in rodents 2,11 but the active phase in humans 27,28 , it is essential to understand the impact of AIH delivered during the daily rest versus active phase. Further, since distinct AIH protocols routinely used in rodents (3, 5 minute episodes) versus humans (15, 1 minute episodes) may differentially impact hypoxia-evoked adenosine release 2 details of the AIH protocol used may also impact respiratory motor plasticity in the rest versus active phases of the day.…”

Section: Introductionmentioning

confidence: 99%

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Daily fluctuations in spinal adenosine determine mechanisms of respiratory motor plasticity

Marciante

Seven

Kelly

et al. 2022

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Plasticity is a fundamental property of the neural system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a prolonged increase in phrenic nerve activity following intermittent exposure to low oxygen (acute intermittent hypoxia, AIH). pLTF arises from distinct intracellular signaling cascades initiated by serotonin and adenosine, respectively, that interact via powerful crosstalk inhibition. We demonstrate serotonin versus adenosine balance varies dramatically with time-of-day and the specific AIH protocol. The fundamental mechanism driving pLTF shifts from serotonin-dominant, adenosine-constrained during rest, to adenosine-dominant, serotonin-constrained in the active phase using our standard AIH protocol. This mechanistic flip results from both daily changes in basal spinal adenosine levels across time-of-day and hypoxia-evoked adenosine release. Since AIH is emerging as a promising therapeutic modality to restore respiratory and non-respiratory movements in people with spinal injury and ALS, new knowledge that time-of-day and protocol impact pLTF mechanisms has experimental, biological and translational implications.

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Section: Introductionmentioning

confidence: 99%