Flip-Flop Switch – A Binary System Balancing Between Sleep and Wakefulness

Last updated: March 6, 2019

Overview

Being sleepy, heavy eyelids, warm bed – before you know it, you’ve fallen asleep. What is this thing that can ’switch us off’ in the evening and ’switch us back on’ in the morning? We know what it feels like to be awake and what it is like to dream, but what is responsible for the transition between these states? In our brains, we have a special complex system which works to keep us awake, transfer us safely into sleep, and keep us there until it transfers us back into wakefulness again every day.

What is the Flip-flop Switch?

Simply put, it is the system in our brains which balances the states of wakefulness and sleep. This system is by scientists imagined as a circuit with two nerve cell groups (called neural populations) which inhibit each other. One such group ensures arousal whereas the other ensures sleep. As we are normally not in an in-between state, each of these neural populations is active only when the other one is ’switched off’.

How Does the Flip-flop Switch Work?

To better understand how this switch works, we have to understand the major components of the whole system. We’ll start off with explaining cells, chemical substances and move on to larger groups of cells.

Neurons and Neurotransmitters

A neuron is a cell of the nervous system. In order to establish communication with other nervous cells and pass information on, it needs a carrier of information. Here come neurotransmitters – efficient chemical compounds which let other neurons know what to do. As long as a neuron receives a message to do something, it will. As soon as it receives a request to stop, it stops. To relate to the beginning of this article – if a group of ’sleep’ cells receives a request to stop being active, that is, to stop telling your brain you’re asleep, the ’wakefulness’ cells take over. This means ’sleep’ cells were inhibited in favor of ’wakefulness’ cells.

Hypothalamus

Hypothalamus is the part of the brain which has many functions in both nervous system and endocrine system (it controls glands and hormonal release). As we are here mostly interested in the nervous system, the following nervous functions are dictated by hypothalamus:

Hypothalamus (more accurately, suprachiasmatic nucleus) controls the circadian rhythm – inner biological clock connected with sleep-wake cycle.

  1. It controls the temperature of the body.
  2. It controls hunger and thirst.
  3. It controls reproduction and the related behavior.
  4. It mediates emotional responses.

Hypothalamus is also known to harbor connections between the eye and the brain. For example, when the eye sensors detect morning light, this information is sent to hypothalamus, which then begins the process of transition into arousal.

Getting Technical

Now that we have learned some basic processes and components of the flip-flop switch model, it is time to dive more in-depth to these neural circuits.

Neurotransmitters responsible for sending the ‘awake’ message are histamine, produced by tuberomammillary nucleus (TMN), and orexin (or hypocretin), produced by other cells called orexin neurons (or hypocretin neurons), located in lateral hypothalamus. Locus coeruleus (LC) is a group of neural cells producing another neurotransmitter – noradrenaline (or norepinephrine), which works similarly to adrenaline, thus its role in keeping the body awake. Finally, a group of cells called raphe nuclei (RN) is the primary producer of serotonin. All of these neurotransmitters are responsible for the state of being awake – they are our brain’s arousal signals.

A different nucleus in hypothalamus inhibits the activity of these nerve populations, promoting sleep – this nucleus is called the ventrolateral preoptic nucleus (VLPO). VLPO is connected with the rest of the nuclei, influencing them by GABA – VLPO’s sleep-inducing neurotransmitter.

However, not only is VLPO able to inhibit TMN, LC, RN and others, but they can also inhibit VLPO – and together they make the two poles of our flip-flop switch. These poles communicate by neurotransmitters, which means they all have receptors for each other’s messages. Thanks to this ‘mutual inhibition’ and good balance of systems, we manage to stay awake or asleep, depending on which system is currently active.

What Does Mutual Inhibition Accomplish?

When we are awake, we stay awake and don’t just randomly fall asleep against our will. This is because VLPO is inhibited, which means all of our arousal cells and signals are active. On the other hand, once we fall asleep, we are less responsive to our surroundings – and it’s good, because we won’t be easily woken up by low-key sounds or dim light.

How Does the ’Switching’ Happen?

In the prolonged state of arousal, certain chemicals (such as adenosine) build up in the brain and tend to shift the balance to the sleep state. However, it is not solely up to chemicals whether sleep neurons are going to be triggered or not. Many factors surrounding us may delay or speed up the sleep onset – sounds, light, relaxation or stress. Other factors are circadian rhythms and homeostatic sleep drive. Only in extreme situations does it happen that someone falls asleep unwillingly – after an unnaturally long period of sleep deprivation, for example.

’When I am tired, I drink coffee and I’m as good as new.’ Most of us are likely to agree with this statement. However, although caffeine is known to wake us up when we are sleepy, what it actually does is blocking the adenosine influence. This means coffee only masks your exhaustion, giving you a feeling you are fresh and rested, but after a hard day’s work, your neurons and your body will still need plenty of rest, even though caffeine won’t make it seem so.

REM and Non-REM Switch

The same on-off switch is observed during the process of sleeping mutually inhibitory neural signals are passed between REM-on and REM-off neurons. REM-on neurons ensure we are in REM phase, whereas REM-off neurons are active during our non-REM (NREM) sleep.

Once we fall asleep, we don’t begin dreaming straight away. We go through different stages of sleep before our dreams visit us.

If the Flip-flop Switch Doesn’t Work Properly…

Destabilization of the flip-flop switch may be suggested by several disorders that mostly go hand-in-hand with severe inconveniences. Here are disorders associated with the faults in the flip-flop switch balance:

  • Narcolepsy is a condition which is characterized by excessive sleepiness, sometimes followed by intrusions of short REM episodes (vivid hallucinations) just before a person falls asleep. Research today shows narcolepsy is linked to the loss of orexin neurons – wakefulness-promoting neurons.
  • Cataplexy refers to episodes of physical paralysis during wakefulness, caused by strong positive emotions – happiness, laughter. It is still unknown why cataplexy is triggered by positive and not negative emotions.
  • Sleep Paralysis carries some similarities to cataplexy, although it is the type of paralysis (muscle atonia) which doesn’t stop after awakening and sometimes may be followed by hallucinations.
  • Hypnagogic hallucinations are strong dream-like sensations which occur just before sleep. For example, as a person drifts off into sleep, they may have a strong feeling that someone is in the room or that they can hear or smell something.

How to Ensure the Switch Flips at the Right Time

It has been reported that these disorders usually do not occur in individuals who are well-rested and healthy. Not paying attention to sleep hygiene – long-term exhaustion, frequent change of sleep time and its duration, excessive usage of caffeine, alcohol or drugs – all can lead to orexin disorders and disorders of circadian system.

Doing relaxing activities in the evenings, eating healthy and exercising during the day, avoiding caffeine in the evenings can help the flip-flop switch remain well-balanced and keep many sleep disorders away.

Additional Resources

  1. Chawla J. What is the flip-flop switch model of sleep regulation? Medscape. September 11, 2018. https://www.medscape.com/answers/1187829-70502/what-is-the-flip-flop-switch-model-of-sleep-regulation Accessed on November 26, 2018
  2. Mandal A. What is the Hypothalamus? News Medical Life Sciences.  https://www.news-medical.net/health/What-is-the-Hypothalamus.aspx Accessed on November 26, 2018
  3. Circadian rhythm and sleep. Sleep Kid. November 14, 2018 https://www.sleepkid.com/circadian-rhythm-and-sleep/ Accessed on November 26, 2018
  4. Under the Brain’s Control. Healthy Sleep. Harvard. December 18, 2007 http://healthysleep.med.harvard.edu/healthy/science/how/neurophysiology Accessed on November 26, 2018
  5. Homeostasis and Sleep Propensity. Sleep Kid. November 14, 2018 https://www.sleepkid.com/homeostasis-sleep-propensity/ Accessed on November 26, 2018
  6. Sleep Deprivation – How Losing Sleep Can Ruin Your Health. Sleep Kid. November 14, 2018 https://www.sleepkid.com/sleep-deprivation/  Accessed on November 26, 2018
  7. Patrick M. Fuller, Clifford B. Saper and Jun Lu. The pontine REM switch: past and present. September 20, 2007 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276987/ Accessed on November 26, 2018
  8. Clifford B. Saper, Patrick M. Fuller, Nigel P. Pedersen, Jun Lu, and Thomas E. Scammell. Sleep State Switching. December 22, 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026325/ Accessed on November 26, 2018

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