Control of Sleep and Wakefulness

Abstract

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems

“…Although it was unexpected that the LC and DR did not increase Fos expression in response to SD in VEH-treated animals, the mixed downstream effects of NE and generally inhibitory effects of 5HT on other wakepromoting cell groups (Brown et al, 2012;Li et al, 2002;Li and van den Pol, 2005) contrast with the excitatory effects of Hcrt, HA, and ACh on these groups , suggesting that the LC and DR may be differentially regulated. The elevated Fos expression observed in the LC following forced wakefulness in ZOL but not VEH or ALM treatment groups is also surprising considering the inhibitory effect of ZOL in other regions, but this may be a result of the greatly increased level of stimulation required to keep ZOLtreated rats awake during forced wakefulness coupled with the high sensitivity of Fos expression in the LC to stress (Sved et al, 2002).…”

Sleep deficits but no metabolic deficits in premanifest Huntington's disease

“…This coupled with the unstable sleep phenotype that we describe in this paper suggests a deficit in neural processes regulating vigilance stages. Sleep and wakefulness result from interacting neurotransmitter systems in the brainstem, hypothalamus, and basal forebrain,63 with sleep emerging from the inhibition of wake‐promoting systems by the preoptic area of the hypothalamus 64. Therefore, it may be that one of the earliest sites of pathology in HD is the hypothalamus 21…”

Activation of the motor cortex during phasic rapid eye movement sleep

“…In our dreams, we can move and perform various complex motor behaviors while being completely motionless due to an atonia of postural muscles 3. How the human motor cortex (Mc) behaves during this state from an electrophysiological point of view remains unknown.…”