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Essential function of sleep clarified / Sleep reduces transmission between nerve cells and thus creates space for new and important things / Publication in Nature Communications

It is still not clear why humans and animals sleep. In a study published in the journal Nature Communications on August 23, 2016, scientists from the Department of Psychiatry and Psychotherapy at the Medical Center - University of Freiburg show that the general activity of the nerve cell connections known as synapses is reduced during sleep. Most connections are weakened, some are even completely broken down. Only important synapses remain or are strengthened. As a result, the brain creates space again to store new information. This adaptability, known as synaptic plasticity, is an important basis for learning and flexible information processing. The degradation should also save space and energy, as both are required to a large extent by the connection points in the brain.

When we absorb information during the day, synapses are strengthened or newly created in the brain. "We have now been able to show for the first time in humans that sleep downregulates the synapses and thus creates space for new information. In other words, the brain cleans up during sleep," says study leader Prof. Dr. Christoph Nissen, Medical Director of the Sleep Laboratory at the Department of Psychiatry and Psychotherapy at the Medical Center - University of Freiburg. "If this process is prevented by a lack of sleep, the brain enters a state of saturation. Synapses can then no longer be sufficiently strengthened or rebuilt. Learning and flexible information processing become correspondingly difficult."

Sleep reduces the increased activity of the synapses during the day

The researchers first examined the general activity of the synapses in the brain, also known as the overall connection strength. Using a magnetic coil above the head of the test subjects, they stimulated an area in the brain that is responsible for controlling a thumb muscle. This procedure is known as transcranial magnetic stimulation (TMS). After sleep deprivation, even a significantly weaker stimulus triggered a contraction of the muscle, which is a sign of a high synaptic connection strength.

The researchers also analyzed the different frequencies of the brain waves using electroencephalography (EEG) measurements. Sleep deprivation led to a significant increase in so-called theta waves. According to previous animal and human studies, this is a further sign of increased overall synaptic strength. "Sleep lowers the overall strength of synapses in the brain that increased during the day. After sleep deprivation, however, the activity remains at a high level," says Prof. Nissen.

Brain defends itself against overload

For the first time in humans, the researchers also found evidence of a principle that ensures permanent stimulus processing, known as homeostatic plasticity. If the synapses are already maximally active due to long periods of wakefulness, new stimuli or information do not lead to a strengthening but to a weakening of the nerve cell connections. New incoming stimuli can then be processed normally again. "It can be assumed that practically all brain functions are influenced by this, such as emotion regulation, concentration or learning," says Prof. Nissen.

In the experiment, the researchers repeatedly combined the stimulation of the motor area of the brain with an electrical stimulus on the arm, which is transmitted to the brain. If the connection between nerve cells is strengthened, the thumb muscle contracts more strongly than before. This effect was seen after a night's sleep. After sleep deprivation, on the other hand, the contraction of the thumb muscle was even weaker. At the behavioral level, the Freiburg researchers also observed poorer relearning of word pairs after sleep deprivation.

Possible reason why people tolerate sleep deprivation differently

They also found evidence that the growth factor BDNF (brain derived neurotrophic factor) plays an important role in the regulation of synaptic activity. It is known that BDNF promotes the reconnection of nerve cells and thus learning after normal sleep. The researchers have now been able to show that a persistently high BDNF concentration in the blood during sleep deprivation tends to lead to a saturation of synapses. "This could explain why some people cope better with sleep deprivation than others," says Prof. Nissen.

Therapeutic approaches for depression and stroke

The findings could contribute to the development of new treatment options, for example after a stroke or for depressive disorders. In these diseases, it is important to change the connections in the brain. Targeted influencing of sleep-wake behavior, but also other methods such as transcranial direct current stimulation or drugs with new mechanisms of action on plasticity could be used for this purpose.

Original title of the paper: Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex

DOI: 10.1038/ncomms12455
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Contact:
Prof. Dr. Christoph Nissen
Medical Director Sleep Laboratory
Department of Psychiatry and Psychotherapy
Medical Center - University of Freiburg
Phone: 0761 270-65010
christoph.nissen@uniklinik-freiburg.de

Further information: Research Group Prof. Nissen