Neuroanatomy of Sleep

WRITTEN BY MAYA GOSZTYLA. Estimated reading time 4 min, 21 seconds
Last update, Dec, 2021

Neuroanatomy of Sleep

We spend a third of our entire lives asleep. For us and most other animals to spend so much time in such a vulnerable state, it must serve some important evolutionary purpose. Yet, surprisingly, scientists still do not fully understand what sleep is and why we do it. Sleep remains an enigmatic but crucial component of our daily lives. This article will give a brief overview of what we do know about sleep and the brain regions controlling it.


Sleep can be broken into two major categories: rapid eye movement (REM) sleep and non-REM sleep. Dreaming occurs during REM sleep, which is why the eyes are often moving beneath the eyelids. Your brain waves during REM sleep appear similar to when you are awake. Non-REM sleep is the deeper form of sleep when it is the most difficult to be awakened, characterized by long and slow brain waves. Throughout the night, you cycle between REM and non-REM sleep several times, which each cycle lasting between 1.5 and 2 hours. Most people will undergo between 4 and 6 sleep cycles per night before beginning to approach wakefulness.


Your brain uses distinct mechanisms to regulate the states of wakefulness, REM sleep, and non-REM sleep. Let’s discuss each of them to understand how they work.


Wakefulness is largely controlled by neurons in the brainstem, which send signals to the brain via two different circuits. The upper circuit goes to a brain region called the thalamus, which controls movement and sensation. People with damage to this circuit are awake but in an unresponsive vegetative state. The lower circuit connects to several brain regions, including the hypothalamus, basal forebrain, and cortex. This circuit is believed to control the conscious experience of being awake, as damage can result in narcolepsy, a disease of excessive sleepiness.



How does this neuronal signaling actually work? Neurons communicate via chemicals called neurotransmitters. There are several neurotransmitters with particular importance for maintaining wakefulness. One example is norepinephrine, which is largely produced in a small brainstem region called the locus coeruleus (Latin for “blue dot”, named for the blue norepinephrine that’s highly concentrated there). These signals are important for inducing hyper-wakefulness during a stressful event, such as a life-threatening emergency. Other examples include orexins, which are required for maintaining long periods of wakefulness, and serotonin, which promotes general wakefulness.


Non-REM sleep is regulated by molecules called somnogens, which gradually accumulate in your body the longer you’re awake and decrease as you sleep. The higher your somnogen levels, the more sleepy you will feel, and as a result, longer periods of wakefulness are followed by longer periods of non-REM sleep. The most well-understood somnogen is adenosine. During wakefulness, adenosine builds up in your brain, causing you to feel more and more tired as the day

goes on. This system is actually how caffeine works: caffeine prevents adenosine from binding to its receptors, thus blocking adenosine signaling and allowing you to feel less sleepy.


Non-REM sleep is largely controlled by the preoptic area, a subregion of the hypothalamus. Preoptic neurons inhibit the wakefulness-promoting signals in the brainstem and hypothalamus, increasing the feeling of tiredness. These neurons fire more quickly the longer you stay awake.


A region of the brainstem called the pons is crucial for REM sleep. Neurons in the pons signal to other neurons in the brainstem medulla and spinal cord in order to produce muscle paralysis. This is why being awakened during REM sleep can sometimes cause “sleep paralysis,” where you are awake but temporarily unable to move. It is also why sleepwalking typically occurs during non-REM sleep, since your muscles are not paralyzed during those stages of sleep.


The neurotransmitters controlling REM sleep remain poorly understood by science. A molecule called acetylcholine appears to be important for entering REM sleep from a non-REM stage. However, the maintenance of REM sleep does not seem to involve acetylcholine. More research is being done to understand this mysterious dreaming stage of sleep.


Behind all of the neural circuitry controlling wakefulness, REM sleep, and non-REM sleep, there’s a single master regulator that’s crucial for it all: the suprachiasmatic nucleus (SCN). A subregion of the hypothalamus, the SCN is your body’s pacemaker for circadian rhythms, which are any biological signaling patterns that follow the day-night cycle.


For our ancient hunter-gatherer ancestors, it would have been crucial to be awake during the day and asleep at night, as the darkness offered protection from predators. To ensure our sleep-wake cycles stay in sync with the day-night cycles, the SCN uses external cues (called zeitgebers, a German word for “time giver”) to predict the time of day and sends signals to the rest of the brain based on this information.


The most important zeitgeber is light, since a decrease in light indicates the end of the day. This is why exposure to bright device screens at night can interfere with sleep, as it tricks your SCN into thinking that it’s still daytime. Another zeitgeber is melatonin, a hormone released by the pineal gland during periods of darkness. Melatonin supplements are poor at promoting sleep, but they can be useful for training your body to adopt a new sleeping pattern, such as getting used to an earlier wake-up time for school or work.


  • Brainstem

    • Rostral brainstem: The rostral brainstem promotes wakefulness by signaling to the cortex via an upper and lower circuit.
      • [Note: “rostral” means “front,” ie the side where the face is.]
    • Pons: REM sleep
      • Locus coeruleus: The locus coeruleus promotes hyper-wakefulness during highly stress events.
    • Forebrain
      • Hypothalamus
        • Caudal hypothalamus: The caudal hypothalamus promotes the conscious experience of being awake.
          • [Note: “caudal” means “back,” ie the side where the back of the head is.]
        • Preoptic area: The preoptic area promotes non-REM sleep by inhibiting wakefulness-promoting signals from other brain regions.
        • Suprachiasmatic nucleus: The suprachiasmatic nucleus keeps your circadian rhythms in sync with the day-night cycle.
      • Basal forebrain: The basal forebrain promotes the conscious experience of being awake.
      • Thalamus: The thalamus promotes sensation and movement during wakefulness.