Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 195

pharyngeal muscles, for instance, contributes to increased resistance and air-
way obstruction. Control of upper airway tone comes from the trigeminal
(CN V), facial (CN VII), and hypoglossal (CN XII) motor neurons. Excit-
atory drive to these pathways comes from cortical and aminergic systems
(i.e., serotonergic, histaminergic, adrenergic, cholinergic systems), is most
robust during wakefulness, and progressively decreases through the different
stages of sleep. Appropriate activity within respiratory muscles (i.e., dia-
phragm and intercostals) is required to pump air through the respiratory
tract. The state dependence of airway control, respiratory muscle activity,
and ventilation will be discussed in more detail below.

2.3. Modulation of breathing
2.3.1 Chemical control of breathing
Arguably, chemical stimuli are the most important regulators of breathing.
The partial pressures of oxygen are mon-

itored by chemoreceptors, which function to maintain blood concentrations
of O 2 ,CO 2 , and serum pH within a narrow range to ensure normal body
tissue function. For the most part, peripheral O 2 chemoreceptors sense
changes in P O 2 , 3 while central CO 2 chemoreceptors sense changes in
P CO 2 . 15 Chemical aberrations, most typically hypoxia or hypercapnia, lead
to activation of the respective chemoreceptor subtype and subsequent mod-
ulation of ventilation to correct the aberration. 15

P O ðÞ and carbon dioxide ð P CO 2 Þ

2.3.1.1 Oxygen chemoreception
The majority of O 2 chemoreception occurs peripherally in the carotid
body by the type I glomus cells. 3 Afferent information regarding P O 2 is sent
via the carotid sinus nerve branch of the glossopharyngeal nerve to the
NTS. 16 Under hyperoxic conditions, carotid sinus nerve fibers fire toni-
cally and increase their discharge rate as P O 2 falls below the normal level
of 100 mmHg. 17 Though most O 2 chemoreception occurs peripherally,
animal models indicate that there is a central component to O 2 chemorecep-
tion. Implicated brain loci include the pre-B¨ tC, 18,19 the ventrolateral
medulla, 20 and hypothalamus. 21 Notably, adult human patients with carotid
body resection do not have a hypoxic ventilatory response, 22 suggesting that
in humans, little O 2 chemoreception occurs centrally.

2.3.1.2 Carbon dioxide chemoreception
In contrast to O 2 chemoreception, the majority of CO 2 chemoreception
occurs within the central nervous system. Neurons in a number of brainstem