Chronic upper airway obstruction induces abnormal sleep/wake dynamics in juvenile rats.

OBJECTIVES: Conventional scoring of sleep provides little information about the process of transitioning between vigilance-states. We used the state space technique to explore whether rats with chronic upper airway obstruction (UAO) have abnormal sleep/wake states, faster movements between states, or abnormal transitions between states. DESIGN: The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed to increase upper airway resistance with no evidence for frank obstructed apneas or hypopneas; 24-h electroencephalography of sleep/wake recordings of UAO and sham-control animals was analyzed using state space technique. This non-categorical approach allows quantitative and unbiased examination of vigilance-states and state transitions. Measurements were performed 2 weeks post-surgery at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep. MEASUREMENTS AND RESULTS: UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. State transitions from light SWS to wake and vice versa and microarousals were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake and light SWS, and increasing deep SWS in UAO. CONCLUSIONS: State space technique enables visualization of vigilance-state transitions and velocities that were not evident by traditional scoring methods. This analysis provides new quantitative assessment of abnormal vigilance-state dynamics in UAO in the absence of frank obstructed apneas or hypopneas

Sleep/Wake Dynamics Changes during Maturation in Rats

<div><p>Objectives</p><p>Conventional scoring of sleep provides little information about the process of transitioning between vigilance states. We applied the state space technique (SST) using frequency band ratios to follow normal maturation of different sleep/wake states, velocities of movements, and transitions between states of juvenile (postnatal day 34, P34) and young adult rats (P71).</p><p>Design</p><p>24-h sleep recordings of eight P34 and nine P71 were analyzed using conventional scoring criteria and SST one week following implantation of telemetric transmitter. SST is a non-categorical approach that allows novel quantitative and unbiased examination of vigilance-states dynamics and state transitions. In this approach, behavioral changes are described in a 2-dimensional state space that is derived from spectral characteristics of the electroencephalography.</p><p>Measurements and Results</p><p>With maturation sleep intensity declines, the duration of deep slow wave sleep (DSWS) and light slow wave sleep (LSWS) decreases and increases, respectively. Vigilance state determination, as a function of frequency, is not constant; there is a substantial shift to higher ratio 1 in all vigilance states except DSWS. Deep slow wave sleep decreases in adult relative to juvenile animals at all frequencies. P71 animals have 400% more trajectories from Wake to LSWS (<i>p</i> = 0.005) and vice versa (<i>p</i> = 0.005), and 100% more micro-arousals (<i>p</i> = 0.021), while trajectories from LSWS to DSWS (<i>p</i> = 0.047) and vice versa (<i>p</i> = 0.033) were reduced by 60%. In both juvenile and adult animals, no significant changes were found in sleep velocity at all regions of the 2-dimensional state space plot; suggesting that maturation has a partial effect on sleep stability.</p><p>Conclusions</p><p>Here, we present novel and original evidence that SST enables visualization of vigilance-state intensity, transitions, and velocities that were not evident by traditional scoring methods. These observations provide new perspectives in sleep state dynamics and highlight the usefulness of this technique in exploring the development of sleep-wake activity.</p></div

Median velocity of juvenile and adult animals.

<p>Box plot shows the median velocity following calculation of the sum of the velocities in each animal.</p

Maturation did not alter velocity.

<p>Velocity is defined as the horizontal and vertical distance between two consecutive points in the point density plot divided by the temporal resolution of 1 second. Plots represent velocities calculated by Pythagorean Theorem for four juvenile (A) and adult (B) animals. Values represent average velocities originating at that site. Warm colors show fast velocities (transition regions) and cool colors slow velocities.</p

Spectral ratios of EEG activity define a 2-dimensional state space with distinct clusters.

<p>(A) control and (B) UAO; spectral ratios of EEG activity define a 2D state space with distinct clusters. Each plot shows 24 hours of EEG activity, and each point represents 1 second of EEG activity. (C) and (D) show 2D state space after application of a Hanning window (20 seconds) of one control and one UAO animal, respectively. Panels A–D: Blue–Wake; Green–slow wave sleep (SWS); Black–paradoxical sleep (PS). Panels E and F: light SWS (LSWS)–green; deep SWS (DSWS)–red.</p

Total time duration in each vigilance state.

<p>Time was calculated by integrating the area under the curve of each vigilance state illustrated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125509#pone.0125509.g001" target="_blank">Fig 1E and 1F</a>. LSWS—light slow wave sleep; DSWS—deep SWS. W—Wake, PS—paradoxical sleep. * <i>p</i> < 0.021—comparing LSWS to DSWS in adult rats.</p

Point densities averaged across all control (A) and UAO (B) animals of the 2D state space plots.

<p>Each plot showed 24 hours of EEG activity, and each point represented 1 second of EEG activity, after application of 20-second wide Hanning window. (C), (D)–“average” state space densities for juvenile and adult animals, projected into ratio 1, respectively. This projection yielded two peaks; left peak was associated with Wake and PS, and the right peak was associated with SWS sleep. (E), (F) Each of the vigilance state space point densities (not shown) was projected separately into ratio 1. Blue—Wake; Black—paradoxical sleep (PS); Green—light slow wave sleep (LSWS); Red—deep SWS (DSWS).</p

Mean number of trajectories between vigilance-states.

<p>Data show the number of spontaneous transitions between behavioral states collected from 456 hours of a rat’s life. W–Wake; LSWS–light slow wave sleep; DSWS–deep slow wave sleep; PS–paradoxical sleep. Values are mean±SEM. (%) Percent of total number of trajectories.</p

Effect of ritanserin on microarousal during the first 6 hours of lights on.

<p>UAO group has significantly more microarousals. Treatment with ritanserin reduces the number of microarousals. **<i>p</i><0.001– comparing baseline vehicle to ritanserin. #<i>p</i><0.05– comparing controls to UAO group.</p