Rapid eye movement (REM) sleep was first identified by its most obvious behavior: rapid eye movements during sleep. In most adult mammals, the electroencephalogram (EEG) of the neocortex is low in voltage during REM sleep. The hip- pocampus has regular high-voltage theta waves throughout REM sleep.
The key brain structure for generating REM sleep is the brainstem, particularly the pons and adjacent portions of the midbrain. These areas and the hypothalamus contain cells that are maximally active in REM sleep, called REM-on cells, and cells that are minimally active in REM sleep, called REM- off cells. Subgroups of REM-on cells use the transmitters gamma-aminobutyric acid (GABA), acetylcholine, glutamate, or glycine. Subgroups of REM-off cells use the transmitters norepinephrine, epinephrine, serotonin, and histamine. It is likely that interactions between REM-on and REM-off cells control the key phenomena of REM sleep.
Destruction of the entire area of midbrain and pons responsible for REM sleep generation can prevent the occur- rence of this state. Damage to portions of the brainstem can cause abnormalities in certain aspects of REM sleep. Of par- ticular interest are manipulations that affect the regulation of muscle tone in REM sleep. Lesions in the pons and medulla cause REM sleep to occur without the normal loss of muscle tone. In REM sleep without atonia, animals exhibit locomotor activity, appear to attack imaginary objects, and execute other motor programs during a state that otherwise resembles REM sleep. This syndrome may have some commonalties with the REM sleep behavior disorder seen in humans. Stimulation of portions of the REM sleep–controlling area of the pons can produce a loss of muscle tone in antigravity and respiratory musculature.
Hypocretin neurons, located in the hypothalamus, con- tribute to the regulation of the activity of norepinephrine, serotonin, histamine, and acetylcholine cell groups and have potent effects on arousal and motor control. Most cases of narcolepsy are caused by a loss of hypocretin neurons.