The Biology Book: From the Origin of Life to Epigenetics, 250 Milestones in the History of Biology (2015)

Reticular Activating System

Horace W. Magoun (1907–1991), Giuseppe Moruzzi (1910–1986)


The reticular formation (RF) consists of nerve pathways that serve as a bridge running through the central core of the brainstem and connecting to the cerebral cortex. The brainstem is an ancient area in the lower portion of the brain that controls functions that are vital for vertebrate survival, whereas the cerebral cortex is the seat of consciousness and thinking. Until the middle of the twentieth century, a state of wakefulness was believed to result from external and internal stimulation of the cerebral cortex, while inhibitory influences produced sleep. Studies conducted at Northwestern University in Chicago in 1949 by Giuseppe Moruzzi and Horace W. Magoun on the RF disproved this concept and provided new insights into sleep and wakefulness.

When Moruzzi and Magoun electrically stimulated the RF, it produced electroencephalographic (EEG) changes that simulated arousal in cats; these effects were observed even after the ascending sensory pathways leading to the cerebral cortex were destroyed. When they produced lesions to the RF, cats became comatose, even when their sensory pathways were left intact.

Thus, the reticular activating system (RAS)—of which the RF is a major component—regulates the progression from deep sleep and relaxed wakefulness to a state of heightened and selective awareness and attention. The RAS serves as a filter, capturing external stimuli that are relevant or novel, while excluding those stimuli that are familiar and repetitive (a process referred to as habituation). Pain signals arising from the lower body travel through the RF to the cerebral cortex, and the RF also integrates cardiovascular, respiratory, and motor responses to external stimuli.

The RAS has both cholinergic and adrenergic nerve influences. Cholinergic nerves—those having acetylcholine as their neurotransmitter—are believed to be the chemical mediators of arousal and wakefulness as well as rapid eye movement (REM) sleep; glutamate, the principal excitatory neurotransmitter in the brain, is also involved. By contrast, adrenergic nerves—with norepinephrine as their neurotransmitter—are active during deep sleep and inactive during REM sleep. Attention deficit disorder may be caused by a deficiency of norepinephrine in the RAS.

SEE ALSO: Medulla: The Vital Brain (c. 530 Million BCE), Nervous System Communication (1791), Neurotransmitters (1920), REM Sleep (1953).

Among the functions of the reticular activating system, as demonstrated in studies of cats, is mediating the shift from a state of relaxation to a period of high attention and arousal.