Sleep Neurobiology

Sleep is the state during which an animal restores energy that has been exhausted during daily activity. Numerous recent research results all point to the fact that the sleeping brain is host of numerous and complex activities that are, at the least partially, at odds with the cerebral activity during wakefulness.

Humans spend between 23% (older adults) and 67% (infants) of their time in sleep. This state includes two major and distinct states: the so-called slow-wave sleep, and paradoxical sleep, also known as rapid eye movement (REM) or active sleep. Although most sleep states can produce dreams, REM dreams are associated with more active and fantastic content.

Sleep can be defined by means of behavioral criteria, such as reduced mobility and responsiveness to external stimuli, characteristic posture, closed eyes, reversible unconsciousness, and electrophysiologic parameters. These parameters, including electrical activity, and ocular movements, are demonstrated on polygraphic recordings of electroencephalograms (EEGs), electromyograms (EMGs), and electrooculograms (EOGs), respectively.

It was then discovered that the brainstem structure basically contains two nuclei (pedunculopontine tegmental and laterodorsal tegmental nuclei) with cholinergic neurons. These neurons have projections that extend towards the thalamus and are further spread by wide-range projections axons everywhere to the cortex. These neurons present high levels of activity during wakefulness and drastically diminish their activity in anticipation of sleep onset.

The cholinergic (acetylcholine-related) activating systems of the brainstem has two targets in the thalamus:

  1. It stimulates the activity of the thalamocortical neurons, also called relay neurons, which generally relay sensory information of various modalities toward the cortex. They release glutamate.
  2. It inhabits the reticular neurons of the thalamus, which receive glutamatergic projections from the cortex and project themselves onto the relay neurons of the thalamus. By releasing γ-Aminobutyric Acid (GABA,) they have an inhibitory action on thalamocortical cells.

Sleep Homeostasis and Circadian Regulation

Like many other vital functions of the animal, sleep is highly regulated. At lease two separate mechanisms have been suggested: One depends on sleep pressure (process S) and the other on circadian rhythms (process C). Sleep deprivation is followed by rebounding intensity in achieving sleep. This homeostatic mechanism proposes the existence of a physiologic indicator that would measure the need for sleep. Adenosine, as a metabolite but also as a neurotransmitter closely related to the levels of vigilance, has been proposed to fulfill this role. Of note is that the stimulating effect of caffeine counteracts the natural mechanism of adenosine. Adenosine promotes sleep by a series of specific presynaptic and postsynaptic mechanisms.

The circadian management of sleep critically depends on the oscillatory behavior of suprachiasmatic neurons. This oscillation which has a period of 24 hours, is rest by light cues arising from the retina during the day and by the levels of melatonin secreted by the pineal gland during the night. The activity of the suprachiasmatic nucleus is relayed by the dorsomedial nucleus of the hypothalamus to reach the ventrolateral preoptic nucleus (VLPO) and orexin neurons in the lateral hypothalamus. The VLPO projection is the inhibitory, thus promoting wakefulness when activated, while the hypothalamus is excitatory (mainly glutamatergic), therefore enhancing wakefulness as well, by boosting neurons.

Recent research has shown that contrary to previous beliefs, glial cells assume an active role in the dialogue with neurons during the beginning of oscillatory patterns. Furhtermore, although sleep activity results from complex interactions among various cerebral structures, cortical as well as subcortical, it is generally excepted that the EEG mainly reflects electrical potentials that are expressed by cortical neurons. Subcortical potentials thus make negligible contributions to the EEG.

Functional role of sleep

Despite better understanding of the mechanisms of sleep, the question of why humans sleep remains unanswered. Life without sleep is impossible.

Furthermore, Sleep might be useful in slowing the production of free radicals, thus reducing oxidative stress. Another theory establishes sleep with the property of enhancing synaptic plasticity for the sake of memory and learning process. Alternatively, some scientists have proposed that sleep is meant to save energy and regulate the synaptic overload undergone during the previous waking period.

The fact that neonates sleep significantly longer than adults might suggest that sleep is essential in growth and development. This idea has received support from experiments in which adult neurogenesis was dramatically reduced after sleep deprivation and may explain why human cognitive performance is impaired by lack of sleep. Increased levels of bacteria in blood after sleep deprivation further suggests diminished immune function, emphasizing the role of sleep in helping to fight or prevent illness.


Although the biologic purpose of sleep is still not fully known, research has shown that the sleeping brain is the host of numerous and complex activities. Sleep can be defined by electrophysiologic parameters such as electrical activity of the brain, muscle activity, and ocular movements. Polygraphic and intracellular recordings of these activities have helped to determine some of the structures responsible for genesis of sleep and the fluctuation among various vigilance states.


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