During the 1920s an obscure disorder that caused encephalitis and attacked the part of the brain that regulates sleep influenced Europe and North America.
He identified the pathways that regulated wakefulness and sleep onset by studying the parts of the brain that were affected by the disease and the consequences it had on the circadian rhythm.
He stated that the pathways that regulated sleep onset are located between the brain stem and the basal forebrain.
His discoveries were not appreciated until the last two decades of the 20th century when the pathways of sleep were found to reside in the exact place that Constantin von Economo stated.
[2] Von Economo, in his studies, noticed that lesions in the connection between the midbrain and the diencephalon caused prolonged sleepiness and therefore proposed the idea of an ascending arousal system.
These neurons are located in the locus coeruleus, dorsal and median raphe nuclei, ventral periaqueductal grey matter, and tuberomammillary nucleus.
[6][7] Further research has shown that the hypothalamic region called ventrolateral preoptic nucleus produces the inhibitory neurotransmitter GABA that inhibits the arousal system during sleep onset.
Levels of acetylcholine, norepinephrine, serotonin, and histamine decrease with the onset of sleep, for they are all wakefulness promoting neurotransmitters.
This had led some to believe that the increase of GABA receptors in the arousal-promoting neurons is another pathway of inducing sleep.
[9] The sleep neurons in the preoptic area receive inhibitory inputs from some of the same regions they inhibit, including the tubermammillary nucleus, raphe nuclei, and locus coeruleus.