Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 206

Figure 8.5 Respiratory stimuli can induce arousal from sleep. (A) Tracing depicting
human arousal from slow-wave sleep in response to an increase in alveolar CO 2 to
7%. After a delay of 60 s after elevation of CO 2 , there is an increase in tidal volume
(V T ) and arousal. Arrow denotes point of arousal. EMG, electromyogram; EEG, electroen-
cephalogram. (B) Bar graph depicting increased waking probability in response to
hypercapnic challenge in lambs. Asterisks denote significant difference compared to
control (p < 0.05). Cross denotes significant difference between vigilance states
(p < 0.001). (C) Four-minute EEG (top), EMG (middle), and P CO ð Þ (bottom) traces from
WT and Lmx1b f/f/p mice showing response to 7% CO 2 . Arousal in the WT mouse is indi-
cated by a decrease in EEG amplitude (and corresponding increase in EEG frequency)
with concomitant increase in EMG amplitude. O 2 level 21% (balance N 2 ) throughout
trace. Scale bars — 30 s and 5 m V. (D) Ninety-second EEG (top), EMG (middle), and P O 2
(bottom) traces from WT and Lmx1b f/f/p mice indicating arousal response to hypoxia
(8% O 2 ). Arousal indicated as in C. Scale bars — 10 s and 5 m V. (A) Redrawn with permis-
sion from Ref. 125 , (B) from Ref. 180 , and (C and D) from Ref. 130 .

arousal from sleep. 130 5-HT neurons, including those in the midbrain which
are involved in sleep-wake regulation, 182-184 are chemosensitive, increasing
their firing rate in response to acidosis in vitro

140

and to increased concentration
of inspired CO 2 in vivo . 145 This likely occurs through a 5-HT 2 receptor-
mediated mechanism. 185 It is thought that CO 2 -induced arousal is mediated
by chemoreceptive neurons in the midbrain since these neurons directly pro-
ject to thalamus and cortex and are thought to be involved in sleep-wake reg-
ulation. 131 A preliminary report suggests that this might be the case. 186
Notably, stimulation of medullary 5-HT neuronal populations can also lead