Brain Primer

How Is Sleep Regulated?

  • Published1 Apr 2012
  • Reviewed15 Aug 2022
  • Author Melissa Galinato
  • Source BrainFacts/SfN
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Most of our lives, we’re in a state of wakefulness — taking in and responding to the world around us. But how does the brain keep us awake?

Wakefulness is maintained by the brain’s arousal systems, each regulating different aspects of the awake state. Many arousal systems reside in the upper brainstem, where neurons connecting with the forebrain deploy the neurotransmitters acetylcholine, norepinephrine, serotonin, and glutamate to keep us awake. Orexin-producing neurons, located in the hypothalamus, send projections to the brainstem and spinal cord, the thalamus and basal ganglia, as well as to the forebrain, the amygdala, and dopamine-producing neurons. In studies of rats and monkeys, orexin appears to exert excitatory effects on other arousal systems. Orexins (there are two types, both small neuropeptides) increase metabolic rate, and their production can be activated by insulin-induced low blood sugar. Thus, they are involved in energy metabolism. Given these functions, it comes as no surprise that orexin-producing neurons are important for preventing a sudden transition to sleep; their loss causes narcolepsy. Orexin neurons also connect to hypothalamic neurons containing the neurotransmitter histamine, which plays a role in staying awake.

The balance of neurotransmitters in the brain is critically important for maintaining certain brain states. For example, the balance of acetylcholine and norepinephrine can affect whether we are awake — high acetylcholine and norepinephrine — or in slow wave sleep (SWS) — low acetylcholine and norepinephrine. During rapid eye movement (REM) sleep, norepinephrine remains low while acetylcholine is high, activating the thalamus and neocortex enough for dreaming to occur; in this brain state, forebrain excitation without external sensory stimuli produces dreams. The forebrain becomes excited by signals from the REM sleep generator (special brainstem neurons), leading to rapid eye movements and suppression of muscle tone — hallmark signs of REM.

During SWS, the brain systems that keep us awake are actively suppressed. This active suppression of arousal systems is caused by the ventrolateral preoptic (VLPO) nucleus, a group of nerve cells in the hypothalamus. Cells in the VLPO release the inhibitory neurotransmitters galanin and gamma-aminobutyric acid (GABA), which can suppress the arousal systems. Damage to the VLPO nucleus leads to irreversible insomnia.

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