Abstract
Neurons containing orexin (hypocretin), or melanin concentrating hormone (MCH) are intermingled with each other in the perifornical and lateral hypothalamus. Each is a separate and distinct neuronal population, but they project to similar target areas in the brain. Orexin has been implicated in regulating arousal since loss of orexin neurons is associated with the sleep disorder narcolepsy. Microinjections of orexin into the brain or optogenetic stimulation of orexin neurons increase waking. Orexin neurons are active in waking and quiescent in sleep, which is consistent with their role in promoting waking. On the other hand, the MCH neurons are quiet in waking but active in sleep, suggesting that they could initiate sleep. Recently, for the first time the MCH neurons were stimulated optogenetically and it increased sleep. Indeed, optogenetic activation of MCH neurons induced sleep in both mice and rats at a circadian time when they should be awake, indicating the powerful effect that MCH neurons have in suppressing the wake-promoting effect of not only orexin but also of all of the other arousal neurotransmitters. Gamma-Aminobutyric acid (GABA) is coexpressed with MCH in the MCH neurons, although MCH is also inhibitory. The inhibitory tone of the MCH neurons is opposite to the excitatory tone of the orexin neurons. We hypothesize that strength in activity of each determines wake vs. sleep.
Highlights
Neurons containing orexin, or melanin concentrating hormone (MCH) are intermingled with each other in the perifornical and lateral hypothalamus
Von Economo performed autopsies on some of the patients who had succumbed to the disease and from his observations he concluded that there was a region in the rostral part of the hypothalamus that was responsible for sleep and a region in the posterior hypothalamus that was responsible for wake
At that time many distinguished scientists were intrigued by sleep and wake centers in the brain and were actively involved in trying to unravel the mysteries of the sleeping brain. One such investigator was Walle Nauta who was conducting his studies during the height of the Second World War in Holland. He wanted to determine whether rats with lesions in the brain, similar to those found in humans by von Economo, could have changes in sleep and wake
Summary
Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep. At that time many distinguished scientists were intrigued by sleep and wake centers in the brain and were actively involved in trying to unravel the mysteries of the sleeping brain One such investigator was Walle Nauta who was conducting his studies during the height of the Second World War in Holland. He wanted to determine whether rats with lesions in the brain, similar to those found in humans by von Economo, could have changes in sleep and wake. It was a simple paper that described regularly occurring periods of eye movements every 90 min or so, and that these periods occurred with a waking EEG
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