Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains

Abstract

The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain interactions. Frequency showed strain (P < 0.0001) and state-by-strain interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13 breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P < 0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.

Automated determination of wakefulness and sleep in rats based on non-invasively acquired measures of movement and respiratory activity

“…Breathing rates also vary among rat strains (Strohl et al, 1997). Mouse strains also differ in sleep amounts (Tang and Sanford, 2002; Veasey et al, 2000), activity levels (Tang et al, 2002), respiration (Friedman et al, 2004; Tankersley et al, 1994; Tankersley et al, 1997), and heart rates (Blizard and Welty, 1971). Being able to non-invasively measure some or all of these variables in rats and mice would provide a tremendous savings in labor.…”

Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse

“…Briefly, we measured breathing data via pressure change across a pressure transducer (Validyne DP45, Validyne Engineering, Northridge, CA, 91324 USA) attached to a reference chamber of 600 ml. For ICV catheter and measurements of sleep, we modified this method by adding a small tube (a “chimney” of 100 ml volume) on the top of the conventional chamber (Friedman et al, 2004). The bottom of this tube is open to the main testing chamber, and the top of this tube is closed with a commutator mounted on the inside ceiling.…”

“…For this analysis, the focus was on spontaneous apneas, defined as a pause for ≥ 2 respiratory cycles (Dias et al, 2009; Yamauchi et al, 2010). For studies of state, the EEG and EMG signals were recorded and analyzed using Somnologica (Embla Systems, Amsterdam, Netherlands), and scored separately (Friedman et al, 2004) into wake, NREM and REM sleep. The files of sleep and breathing were merged using common time signals and results compiled for pauses according to state.…”

Loop Gain and Sleep Disordered Breathing

“…It turns out that inheritance influences a significant proportion of ventilatory rate and rhythm and the response to hypoxia and hypercapnia [64,65], a concept directly supported by studies in knock-out animals [66,67]. In the study of naturally occurring variations, an interplay of a few major genes appear to influence the level of ventilation on hypoxia [31], and the finding of differences in the pattern of breathing among strains in wakefulness, slow wave sleep, and active sleep [68] implies that genetic background strongly affects features of breathing rate and ventilatory behavior despite broad changes in state.…”