REM Sleep Rebound Following Acute Intermittent Hypoxia in Freely Behaving Rats

Abstract

Core components of the circadian clock and molecules involved in neuroplasticity elicited by acute intermittent hypoxia (AIH) exhibit 24‐hour rhythms in gene expression in the phrenic/diaphragm motor system. Ongoing investigations of time‐of‐day effects on AIH‐induced motor plasticity must account for changes in time spent across vigilance states since sleep architecture profoundly influences other biological rhythms across the rest‐active cycle. Previous investigations from our group reported a marginal increase in wakefulness during the AIH exposure in unanesthetized rats (10, 5‐min hypoxic episodes; 5 min intervals). Following AIH, we also observed a prolonged increase in slow‐wave sleep lasting hours, but changes in REM were not assessed (Terada et al., J. Appl. Physiol., 2011). Given the significant effects disruptions of the sleep‐wake cycle can have on daily biological rhythms, further characterization of sleep architecture following AIH is needed. In this preliminary analysis, from an extensive study of diaphragm long‐term facilitation (LTF) in rats at opposite stages of the diurnal cycle (mid‐active vs. mid‐rest), we added second set of intracortical EEG leads (ECoG) not used by Terada et al. (2011) to enhance detection of hippocampal theta bursts and sleep spindling. In 8 unanesthetized, instrumented rats exposed to AIH, ECoG, and nuchal EMG signals acquired via radiotelemetry were analyzed in 10‐second epochs using Fast Fourier transformation spectral analysis. Power spectra were averaged in frequency bands: delta (1.5‐4.0Hz), theta (4.0‐10.0Hz), beta (10.0‐30.0 Hz), and sigma (10.0‐14.0Hz). We assessed vigilance state at baseline, during AIH, and 90 minutes post‐AIH; there were significant effects of AIH protocol period (p < 0.05) and sleep state (p<0.001). There were marginal, non‐significant trends towards increased active wakefulness during AIH, with decreased quiet wakefulness, slow‐wave sleep, and REM. Time spent in REM sleep rebounded to levels nearly two‐fold above baseline at 60 and 90 min post‐AIH; there were non‐significant trends towards reduced quiet wakefulness without apparent change in NREM sleep post‐AIH. In this preliminary analysis, we report an acute AIH protocol (3, 5 min hypoxic episodes, 13% O2; 5‐min normoxic intervals) has minimal impact on NREM sleep during or following AIH but increases REM post‐AIH. Additional analyses will be performed during and following AIH during the mid‐active and mid‐rest phases, using the 5‐min AIH protocol and a modified protocol with similar cumulative duration of hypoxia (15, 1 min hypoxic episodes; 1 min intervals) often used in human studies of repetitive AIH as a neurotherapeutic modality to improve breathing and non‐respiratory motor function in humans living with chronic spinal cord injury and ALS. REM sleep is essential for mechanisms of neuroplasticity in neural networks controlling diverse physiological systems. These results warrant future research to delineate the influence REM may play in initiating and maintaining memory in the respiratory system.