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.

/pdf/control-of-sleep-and-wakefulness-51vkuya5ho.pdf

Control of Sleep and Wakefulness

The rostral hypothalamus and adjacent basal forebrain participate in the generation of sleep, but the neuronal circuitry involved in this process remains poorly characterized. Immunocytochemistry was used to identify the FOS protein, an immediate-early gene product, in a group of ventrolateral preoptic neurons that is specifically activated during sleep. The retrograde tracer cholera toxin B, in combination with FOS immunocytochemistry, was used to show that sleep-activated ventrolateral preoptic neurons innervate the tuberomammillary nucleus, a posterior hypothalamic cell group thought to participate in the modulation of arousal. This monosynaptic pathway in the hypothalamus may play a key role in determining sleep-wake states.

https://science.sciencemag.org/content/sci/271/5246/216.full.pdf

Activation of Ventrolateral Preoptic Neurons During Sleep

Restoration of brain energy metabolism as the function of sleep.

Animal sleep: A review of sleep duration across phylogeny

Publisher Summary This chapter presents the genesis of the electrocorticogram to provide a basis for understanding the nature of cortical activation. Cortical activation is attributed to an action of the ascending reticular activating system. The chapter discusses new evidence showing that cortical activation is dependent on both cholinergic and serotonergic inputs to the neocortex. Ascending cholinergic and serotonergic pathways innervate both the thalamus and the neocortex. It may be that the thalamus and the cerebral cortex are activated in parallel and that thalamic activation is not the primary cause of neocortical activation. The only known means of producing a total loss of cortical activation is deep anesthesia or acute transection of the brainstem. A combination of p -chlorophenylalanine and scopolamine that provides a convenient means of abolishing cerebral cortical activation, produces deficits in self-stimulation behavior, which are similar to those produced by a combination of reserpine with atropine or scopolamine plus amphetamine. Blockade of cerebral cortical activation may be the principal (though undoubtedly not the only) mechanism by which centrally acting antimuscarinic and antiserotonergic drugs affect both learned and unlearned behavior. It is argued that the cholinergic projections from the basal forebrain to the cerebral cortex are responsible for an atropine-sensitive component of cortical activation.

M.B. Sterman

Papers

Effect of a forebrain lesion on the polycyclic sleep-wake cycle and sleep-wake patterns in the cat

Effects of brain surgery and EEG operant conditioning on seizure latency following monomethylhydrazine intoxication in the cat.

The polycyclic sleep-wake cycle in the cat: Effects produced by sensorimotor rhythm conditioning

Sleep and kindling: II. Effects of generalized seizure induction

Effects of sensorimotor EEG feedback training on seizure susceptibility in the rhesus monkey.