Program in Mechanisms of Regulation of Sleep

The Program in the Mechanisms in the Regulation of Sleep represents a collaboration between the Laboratory of Integrative Neurobiology and the Division of Sleep Disorders.

Individual laboratories are run by Drs. Saper, Scammell, Chamberlin, and Lu.

The basic science component of this program uses electrophysiological and neuroanatomical techniques to dissect the circuitry within the brain that regulates wake-sleep cycles. Current work is focused upon a recent finding from this laboratory, that there is a specific group of nerve cells in the ventrolateral preoptic area which is the only cluster of neurons in the brain that demonstrates increased activity (as measured by expression of the Fos protein) during sleep. These neurons have connections with the major arousal systems of the brain and use inhibitory neurotransmitters, and they may serve as a central switching mechanisms for turning off the arousal systems to allow sleep to occur. We are currently investigating the mechanisms that may drive the ventrolateral preoptic area to cause sleep.

The Program in the Mechanisms in the Regulation of Sleep represents a collaboration between the Laboratory of Integrative Neurobiology and the Division of Sleep Disorders.

The basic science component of this program uses electrophysiological and neuroanatomical techniques to dissect the circuitry within the brain that regulates wake-sleep cycles. This work focuses on 4 major topics:

  1. We identified a specific group of nerve cells in the ventrolateral preoptic area that is active during sleep (as measured by expression of the Fos protein). These neurons connect with the major arousal systems of the brain and use inhibitory neurotransmitters, and they may serve as a central switching mechanisms for turning off the arousal systems to allow sleep to occur. We are currently investigating the mechanisms that may drive the ventrolateral preoptic area to cause sleep.
  2. People with narcolepsy have chronic sleepiness, and episodes of muscular weakness or paralysis known as cataplexy. Narcolepsy is due to a loss of neurons in the lateral hypothalamus that produce narcolepsy. To improve our understanding of narcolepsy, we are studying brain pathways that produce narcolepsy in mice and rats. In addition, we are studying the brains of people with narcolepsy and investigating whether people with narcolepsy have abnormalities in appetite or metabolism.
  3. Sleep and wakefulness are strongly influenced by circadian rhythms, 24 hour rhythms that time nearly all biological functions. We have found that the daily rhythms of wakefulness and body temperature are mediated by specific brain regions, and current work is focussed on identifying the connections and signaling molecules used by these regions.
  4. The mechanism through which anesthetics produce unconsciousness is unknown but our group has found that some commonly used anesthetics produce sleep by activating nerve cells in the ventrolateral preoptic area. Continued work in this area should lead to the development of better anesthetics and sleeping pills.

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