Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 205

response to hypoxia, with the responses being less robust in NREM and
even lower in REM. 173-176
Direct stimulation of respiratory control regions including RTN, NTS,
lateral hypothalamic orexin neurons, and caudal 5-HT neuronal populations
(RPa, ROb, RMag) with acidosis modulates breathing. 34,37,56,143,177,178
These and other sites within the caudal brainstem have been identified as
putative respiratory chemoreceptors. The reason for the distributed nature
of central respiratory chemoreception has been postulated to revolve around
the state dependence of respiratory chemoreception. 25,80 Indeed, there are
state-dependent differences in the ability of direct stimulation of the differ-
ent sites with acidosis to affect breathing. 179 For example, direct stimulation
of the RTN with acidosis is now thought to increase tidal volume during
wakefulness, whereas stimulation of the rostal medullary raph´ (raph´ mag-
nus) is most effective during sleep. Stimulation of the caudal medullary raph´
(raph´ obscuris) is relatively ineffective in sleep and wakefulness, but
enhances the chemosensitivity of the RTN during wakefulness. 80
4.2. Influence of breathing on sleep
Just as sleep state can influence respiratory control, changes in breathing can
cause alterations in vigilance state. As discussed above, changes in breathing
occur normally as a result of vigilance-state transitions and during dreaming.
Breathing changes can also be induced due to untoward circumstances, such
as cessation of airflow due to central or obstructive sleep apneas (OSAs) and
as a result of noxious stimuli encountered during sleep. The most important
chemical modulators of breathing, hypoxia and hypercapnia, are potent
arousal inducers ( Fig. 8.5 ) . 125-127,129,130,132,133,180
As discussed earlier, the concentration of CO 2 in the blood is regulated
by breathing and is responsible for preserving respiratory drive. While the
CO 2 set point is higher during sleep, additional elevations above this thresh-
old might be encountered during sleep due to sleep apnea and poor air
exchange or excessive rebreathing of expired CO 2 -rich air. The former,
of course, is a significant mechanism in OSA, while the latter is postulated
to be a significant mechanism in the sudden infant death syndrome
(SIDS). 130,181
Mice with a genetic absence of serotonin neurons in the central nervous
system ( Lmx1b f/f/p ) have impaired arousal toCO 2 ( Fig. 8.5 ) , but display normal
arousal to other stimuli, including hypoxia, sounds, and mechanical stimula-
tion, indicating a specific involvement of 5-HT neurons in CO 2 -induced