Intermittent but not sustained moderate hypoxia elicits long-term facilitation of hypoglossal motor output.

Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent respiratory motor plasticity induced by moderate acute intermittent hypoxia (AIH), but not by moderate acute sustained hypoxia (ASH) of similar cumulative duration. Thus, moderate AIH-induced pLTF is sensitive to the pattern of hypoxia. On the other hand, pLTF induced by severe AIH protocols is neither pattern sensitive nor serotonin dependent (it converts to an adenosine-dependent mechanism).

Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury.

Spinal injury disrupts connections between the brain and spinal cord, causing life-long paralysis. Most spinal injuries are incomplete, leaving spared neural pathways to motor neurons that initiate and coordinate movement. One therapeutic strategy to induce functional motor recovery is to harness plasticity in these spared neural pathways.

5-HT3 receptor-dependent modulation of respiratory burst frequency, regularity, and episodicity in isolated adult turtle brainstems.

To determine the role of central serotonin 5-HT(3) receptors in respiratory motor control, respiratory motor bursts were recorded from hypoglossal (XII) nerve rootlets on isolated adult turtle brainstems during bath-application of 5-HT(3) receptor agonists and antagonists. mCPBG and PBG (5-HT(3) receptor agonists) acutely increased XII burst frequency and regularity, and decreased bursts/episode. Tropisetron and MDL72222 (5-HT(3) antagonists) increased bursts/episode, suggesting endogenous 5-HT(3) receptor activation modulates burst timing in vitro.

Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation.

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). We hypothesized that: 1) daily AIH (dAIH) preconditioning enhances phrenic and hypoglossal (XII) LTF in a rat strain with low constitutive LTF expression; 2) dAIH induces brain-derived neurotrophic factor (BDNF), a critical protein for phrenic LTF (pLTF) in the cervical spinal cord; and 3) dAIH increases post-AIH extracellular regulated kinase (ERK) activation. Phrenic and XII motor output were monitored in anesthetized dAIH- or sham-treated Brown Norway rats with and without acute AIH.

Okadaic acid-sensitive protein phosphatases constrain phrenic long-term facilitation after sustained hypoxia.

Phrenic long-term facilitation (pLTF) is a serotonin-dependent form of pattern-sensitive respiratory plasticity induced by intermittent hypoxia (IH), but not sustained hypoxia (SH). The mechanism(s) underlying pLTF pattern sensitivity are unknown. SH and IH may differentially regulate serine/threonine protein phosphatase activity, thereby inhibiting relevant protein phosphatases uniquely during IH and conferring pattern sensitivity to pLTF.

Role of synaptic inhibition in turtle respiratory rhythm generation.

In vitro brainstem and brainstem-spinal cord preparations were used to determine the role of synaptic inhibition in respiratory rhythm generation in adult turtles. Bath application of bicuculline (a GABA(A) receptor antagonist) to brainstems increased hypoglossal burst frequency and amplitude, with peak discharge shifted towards the burst onset. Strychnine (a glycine receptor antagonist) increased amplitude and frequency, and decreased burst duration, but only at relatively high concentrations (10-100 microM).