Chapter 7 - Neural Control of Sleep in Mammals

Abstract

Mammalian sleep and wake states are regulated by multiple neuronal systems located in the brainstem, diencephalon, and telencephalon. Arousal and waking are facilitated by chemically distinct neuronal groups localized in the pons, midbrain, posterior and lateral hypothalamus, and basal forebrain. Functionally important arousal systems include glutamatergic, histaminergic, orexinergic, serotoninergic, cholinergic, dopaminergic, and noradrenergic neurons. Arousal systems have widespread projections that regulate global aspects of arousal, including changes in electroencephalographic, motor, sensory, autonomic, and integrative functions. Arousal systems control the excitability of thalamic and cortical neurons. Reduced activity in arousal systems promotes synchronous discharge of intracortical and thalamocortical circuits that underlie NREM sleep patterns on the electroencephalogram. The preoptic anterior hypothalamic area (POA) contains gamma-aminobutyric acid (GABA)-ergic/galaninergic neurons that exhibit increased activity during NREM and REM sleep and respond to physiologic signals that increase sleep, sustained wakefulness, and endogenous sleep factors. POA sleep-active GABAergic neurons project to histaminergic, orexinergic, serotoninergic, and noradrenergic arousal systems and, through coordinated inhibition of these arousal systems, promote transitions from waking to sleep. GABAergic sleep-promoting neurons are also localized in the medullary parafacial zone and exert sleep-related inhibition of wake-promoting glutamatergic neurons in the parabrachial nucleus in the pons. Sleep-promoting molecules are related to the multiple functions of sleep: adenosine to resupply brain energy reserves, cytokines to facilitate immune functions, growth hormone–releasing hormone to promote anabolic processes, unfolding protein response signals to prevent protein misfolding, and oxidative stress signaling molecules to prevent oxidative stress–induced cell damage.