Control of the cardiovascular and respiratory systems during sleep.

Sleep and arousal from sleep are associated with profound changes in cardiovascular and respiratory functions. Fluctuations of arterial blood pressure (ABP), heart rate (HR), and respiration occur both during non-rapid eye movement (NREM) and REM sleep and during transitions between sleep and behavioral arousal. These changes reflect complex, state-dependent interactions among several neuronal groups in the hypothalamus and brainstem. These neurons utilize the excitatory amino-acid L-glutamate or the inhibitory amino acid γ-aminobutyric acid (GABA) and are modulated in a state-dependent manner by inputs from cholinergic, monoaminergic, and hypothalamic orexin/hypocretin and melanin-concentrating hormone (MCH) neurons. These different neuronal populations mediate continuous interactions between cortical state and subcortical circuits modulating sympathetic and cardiovagal output, respiratory pattern, and chemosensitivity. Reciprocally, brainstem areas involved in these functions promote behavioral arousal in the setting of hypoxia, hypercapnia, or other stressors. Studies in rodents using optogenetic and other approaches for selective activation or inactivation of specific neuronal groups identified by their unique neurochemical markers, combined with recording of cortical activity, cardiovascular responses, and respiration, have provided new information on the brainstem mechanisms controlling arousal, wake-sleep cycle, cardiovascular and respiratory control (Luppi et al., 2017; Saper and Fuller, 2017; Scammell et al., 2017; Dampney, 2016; Del Negro et al., 2018; Guyenet, 2006; Guyenet and Abbott, 2013; Smith et al., 2013). These findings also provide further insight into the pathophysiology of sleep-related cardiovascular and respiratory disorders including sleep apnea, narcolepsy, congenital central hypoventilation syndrome, sudden infantile death syndrome, and sudden unexpected death in epilepsy.