How Sleep “Reboots” Your Brain

Last updated: March 6, 2019

We all feel great – happy, energetic and optimistic after a good night’s sleep. Having enough deep and REM sleep surely improves mood and attention. But how does sleep make us feel and perform better?

Recent studies have found the key process for understanding how the brain clears out from substances that accumulate during wakefulness. What happens is that nerve cells “shrink”, and when they become smaller, for one, it is easy for them to refresh and two, they leave a lot of space for those substances to get “washed out” from the system.

Brain plasticity theory and sleep

One of several theories on why we sleep is the brain plasticity theory. According to this explanation, sleep is necessary for our brain to restructure and reorganize. Plasticity refers to the brain’s ability to change.

Sleep helps with our memory consolidation – and memory consolidation (transferring from short-term into long-term memory, together with forgetting unnecessary information) has a mental and physical aspect.

The mental aspect is simply remembering certain information or not. But physical changes that lead to this are seen through nerve cell interconnection. Nerve cells, or neurons, are linked with other neurons through short (dendrites) and long (axon) “branches” of the cell. The spots in which they almost touch other neurons are called synapses. Each receiving neuron gets information through its receptor.

Neurotransmitters are the information carrier chemicals and they are discharged from one neuron into the synapse and to the receptor of the next neuron, which transfers information on.  

When we learn new things, our brain cells make new synapses – and this is how the brain structure changes.

After sleep, some synapses are strengthened and some are weakened. By “sieving” through the information and making the corresponding structural changes, our brain makes space for more cognitive tasks, like learning, paying attention and recalling. We feel refreshed and ready for new challenges.


Figure 1. Anatomy of Neurons

Fluids of the brain – glymphatic system

Glymphatic system or paravascular system is a pathway through which neural environment is cleared from waste. It stretches throughout the central nervous system (CNS). Cerebrospinal fluid flows through this space, and it is especially significant for clearing out metabolic nerve cell products while we sleep, that is when the neurons shrink and make more space for clearance.

The glial cells which surround neurons control this system by either shrinking or swelling. A chemical called noradrenaline (wakefulness promoting) makes them swell, while they shrink under sleep-promoting chemicals.

If we don’t sleep well and long enough, we will face the following day dragging the brain waste from the previous day (or days). This physically obstructs the process of thinking.

How the brain changes while we sleep

Three notable studies published in the journal Science look into the matter of brain change during sleep. In one of them, researchers made 3D reconstructions of mouse brains using the latest technology to track neuronal changes during sleep. The second study found biochemical proof for the same thing – the number of synapses shrank for about 20%, increasing the intercellular space and allowing the cerebrospinal fluid to wash away nerve cell products. These two were published in 2017. The third and oldest one, from 2013, focused on how much space between brain cells increases and how it is related to clearance of beta-amyloid (a chemical whose plaque is found in people suffering from Alzheimer’s disease).

Serial scanning 3D electron microscopy study

The particular parts of the mouse brain observed in this study were two areas of the cerebral cortex involved in sensory and motor information intake. They wanted to see how the brain changes by performing a complicated procedure of scanning a large number of thin slices of the brain, which allowed the researchers to use each scan as an image to create an extremely detailed 3D image. It goes into such detail that individual neurons can be observed.

This further allowed scientists to measure synapses. Synapses are the only way for any two neurons to interact, and their size is a sign of their strength. Stronger synapses correspond to stronger memory and their plasticity is low, whether short and weak synapses are very prone to change until they become stabilized.

As mice are nocturnal animals, they are active throughout the night and sleep during the day. In this study, mice were examined on their natural circadian schedule as well as on a changed schedule – they were kept occupied during the day with new objects and left to sleep at night. The same effects of sleep persisted in both cases.

Altogether, about 6,900 synapses were measured. While mice were active and engaged, their synapses grew in size and strength. However, after about 7 hours of sleep (one hour more or less), those very synapses retreated by about 20%.

Not all synapses behaved in the same way. The weakest ones saw the biggest change, whereas the strongest synapses remained quite stable. This could mean that stable synapses correspond to stronger memory so they are not affected by sleep “cleanup”.

The whole process refreshes or “reboots” the brain, leaving it ready for the new day and new synapse growth.

Synapse change is driven by a protein Homer1a, which is encoded in a gene of the same name, HOMER1A.

Protein Homer1a as a driver of synapse change study

This study used a biochemical approach, also in mice, to see how sleep helps with learning and memory. Although completely unrelated to the first study, the researchers came to the same conclusion about synapse strength.

They also embarked into proteomics (the study of proteins contained in one cell at a time) and used imaging to get more accurate results.

The researchers of this study found that during sleep the receptors for proteins decreased by about 20%. They also pointed to a particular protein, Homer1a, keeps rising during a good and long night’s sleep. Homer1a is one of the proteins which play an important role in sleep and wakefulness, but here it was also found that its presence is what “reboots” the brain.

If there was a lack of Homer1a protein, the refreshment in the morning also lacked, which may explain why we feel bad after a short sleep. This protein seems to respond to certain chemicals which indicate tiredness (adenosine), or wakefulness (noradrenaline). It increases when noradrenaline is low, and adenosine high, that is – when the animals are asleep.

The authors suggest that their findings indicate that this downscaling in the brain is an important factor in contextual memory consolidation.

Metabolism product clearance during sleep

The study which perhaps influenced the above mentioned two used in-vivo two-photon imaging, a technique which allows seeing tissues of living subjects. The researchers found an increase of 60% in the space between cells and a clearance rate faster than that in the awake animals.

The cerebrospinal fluid flux caused rapid beta-amyloid clearance during sleep. High accumulation of beta-amyloid and other substances have been linked to serious neural diseases, like Alzheimer’s disease. The glymphatic system is not able to clear the brain during wakefulness as efficiently as it is during sleep.

Proper sleep could prevent accumulation of these substances and likely lessen the chances of developing neurodegenerative diseases.

Another interesting observation in this study is that the fluid moved rapidly regardless of whether mice were sleeping or in anesthesia. Although able to clear out during anesthesia, it doesn’t mean that the state of anesthesia equals sleep.

The clinical significance of this study lies in the possibility of prevention of some diseases through the glymphatic system manipulation. The scientists hope to find a way to help the brain clear out from plaque buildup.

If the brain doesn’t clear properly

In case there is a glymphatic system disorder or simply a person suffers from long-term sleep deprivation, the brain is prevented from the chance to remove all the nerve cell waste that accumulates during the day.

This results in poor attention and thinking skills and low learning capacity. In the long run, it can lead to the accumulation of wasteful substances which are then referred to as neurotoxins, because in large quantities, they are harmful to nerve cells and can even kill them.

Summary

Sleep “reboots” the brain though shrinking nerve cells and their synapses. While Homer1a directs this process, the space between cells increases significantly, which allows the cerebrospinal fluid to flow quickly and freely, flushing away the waste from nerve cell activity.

The brain is refreshed and ready for new challenges. If it doesn’t clear out properly, its functions are slower and less efficient. In cases where this persists for years, a person might be at very high risk of developing neural disorders.

Therefore, we should make sure to have enough sleep and pay special attention to our sleep hygiene, because our success and health depend on it.

Additional resources

  1. De Vivo L, Bellesi M, et al. Ultrastructural evidence for synaptic scaling across the wake/sleep cycle. Science. February 03, 2017.   https://www.ncbi.nlm.nih.gov/pubmed/28154076 Accessed March 4, 2019.
  2. Diering G. H, Nirujogi R. S, et al. Homer1a drives homeostatic scaling-down of excitatory synapses during sleep. Science. February 03, 2017.  https://www.ncbi.nlm.nih.gov/pubmed/28154077 Accessed March 4, 2019.
  3. Xie L, Kang H, et al. Sleep drives metabolite clearance from the adult brain. Science. October 18, 2013. https://www.ncbi.nlm.nih.gov/pubmed/24136970 Accessed March 4, 2019.

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