The study shows that the brainstem region is involved in the organization of sleep

Scientists from the University of Lausanne have identified a new role for the brain’s “locus coeruleus” during sleep and sleep disruption. This area of ​​the brain facilitates the transition between NREM and REM sleep states while maintaining unconscious alertness to the outside world. Stress disrupts its functions and negatively affects the quality of sleep.

Sleep disorders affect more and more people, which can have serious consequences for their health. Mammalian sleep consists of cycles between two states: non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. However, the principles governing these cycles remain poorly understood.

Research led by Professor Anita Lüthi, a researcher at the Department of Fundamental Neurosciences at the Faculty of Biology and Medicine of the University of Lausanne (UNIL), shows for the first time that the locus coeruleus (LC), an area of ​​the brainstem, is involved in the organization of sleep.

Until now, LC has been known to be the primary regulator of the ability to respond to challenging situations while awake rather than asleep. Study conducted by Anita Lüthi and published in: Life neuroscience now shows that the LC determines when a transition between two sleep states is possible, showing that this brain region is crucial for the normal cycling of sleep states.

Moreover, the team found that daytime experiences, especially stress, disrupt LC activity during sleep and result in disorganized sleep cycles and frequent awakenings. These findings provide key insights for improved understanding sleep disorders and may lead to improved treatments.

A new definition of sleep structure

The LC, long recognized as the center of noradrenaline production – the primary hormone that regulates our ability to respond to environmental challenges by mobilizing the brain and body – is essential for cognitive wakefulness.

During sleep, its activity fluctuates, alternating between peaks and troughs at intervals of about 50 seconds. The role of this activity has so far been poorly understood. Thanks to the implementation of advanced technologies, neurobiologists from UNIL were able to select neuronal pathways in this area of ​​the mouse brain.

“We found that both the peaks and troughs of variable LC activity play a key role in the organization of sleep. This is a new structural element of sleep that works a bit like a clock,” explains Georgios Foustoukos, one of the three main authors of the study.

Their results show that sleep consists of previously unknown structural units during which two functions are sequentially coordinated. During peaks in LC activity, part of the subcortical brain enters a more wake-like state thanks to norepinephrine, enabling unconscious alertness to the environment and potential threats. Conversely, during valleys it is possible to transition into REM sleep.

Two key functions of restorative sleep

Under normal conditions, human NREM sleep consists of four distinct stages that comprise the deepest stages of sleep. REM sleep, on the other hand, is characterized by high brain activity associated with dreams and takes up about a quarter of an hour of the night.

On a typical night, NREM and REM states alternate in a coordinated manner, allowing the body and mind to rest and recuperate. UNIL neuroscientists have identified the LC as the gatekeeper of these transitions, precisely controlling when the transition from NREM to REM sleep can occur, especially at times when its activity is low.

Conversely, scientists have found that when LC activity is elevated, more norepinephrine is released into the brain, making certain areas of the brain more susceptible to stimulation without waking the body. This state represents a previously unknown type of arousal that generates alertness to the surroundings and body during sleep, facilitating complete and rapid awakening in an emergency situation.

“In other words, the brain is partially awake at the subcortical level, while it is asleep at the cortical level,” says Anita Lüthi.

Hope for sleep disorders

Another important finding from this study is the observation that stressful experiences during wakefulness in mice can disrupt sleep by increasing LC activity, which delays the onset of REM sleep and fragments NREM sleep, causing too many awakenings. They concern both subcortical and cortical parts of the brain.

For Anita Lüthi, the results pave the way for new clinical applications for people suffering from sleep disorders. “Our findings may help better understand sleep disorders associated with mental health disorders such as anxiety or other sleep disorders.

“Moreover, they offer opportunities for new therapies, such as using LC as a biomarker to monitor and potentially correct sleep cycles. The power of our work is that we use the neural activity of the sleeping person brain This is a big step towards measuring human sleep as we know it from hospitals,” says Lüthi.

A clinical collaboration was initiated with the University Hospital of Lausanne (CHUV) to assess whether the mechanisms identified in mice could be applied to human sleep.

Finally, the study also provides clues to better understand sleep through species evolution. Unlike mammals with two clearly distinct sleep states, some archaic species, such as reptiles, do not exhibit such a well-defined duality. However, several reptiles have two types of sleep that alternate for about 50 seconds. This suggests that precursors of LC activity already existed to structure their ancient sleep.