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

Abstract

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). Although moderate AIH also induces hypoglossal LTF (hLTF), no data are available concerning its sensitivity/insensitivity to the pattern of hypoxia. Since hLTF following moderate hypoxia is serotonin-dependent, we hypothesized that hLTF is pattern-sensitive, similar to serotonin-dependent pLTF. Integrated hypoglossal nerve activity was recorded in urethane-anesthetized, vagotomized, paralyzed, and ventilated rats exposed to isocapnic AIH (3, 5min episodes of 11% O₂) or ASH (a single 25min episode of 11% O₂). Similar to previous studies of pLTF, hypoglossal motor output was elevated for more than 1h following AIH (50±20%, p<0.01), but not ASH (-6±9%, p>0.05). Frequency LTF was not observed following either hypoxic exposure. Thus, in agreement with our hypothesis, hypoglossal LTF following moderate AIH is pattern-sensitive, similar to phrenic LTF.

Keywords: Control of breathing; Hypoxia; Pattern; Plasticity.

Figure 1.. Intermittent, but not sustained, hypoxia, elicits long-term facilitation (LTF) of hypoglossal (XII) motor output.

Representative integrated hypoglossal neurograms before, during, and 60 min following intermittent (top) or sustained (middle) hypoxia or no hypoxia (time control, bottom). Relative to baseline (indicated by dotted line), hypoglossal burst amplitude was increased 60 min following intermittent, but not sustained hypoxia. When hypoxia is not presented, hypoglossal motor output remains stable over time (time control). Short bar = 5 min; long bar = 25 min.

Figure 2.. Hypoglossal (XII) motor output is similar during intermittent or sustained hypoxia.

Short-term response of hypoglossal burst amplitude (A) and frequency (B) during intermittent or sustained hypoxia or without hypoxia. Data are presented as mean ± SEM. * Significantly increased from baseline (p < 0.05)

Figure 3.. Long-term facilitation (LTF) of hypoglossal (XII) burst amplitude, but not burst frequency, is observed following intermittent, but not sustained, hypoxia.

XII burst amplitude (A) but not delta burst frequency (B) is enhanced 60 min following intermittent, but not sustained hypoxia. Data are presented as mean ± SEM. *Significantly increased from baseline (p < 0.05).