Exploring the mysteries of sleep

Mattia Aime from the Department for BioMedical Research has discovered how sleep helps to process emotions. For this he receives a Pfizer Research Prize, one of the most prestigious medical prizes in Switzerland.

Dr. Mattia Aime, Department for BioMedical Research (DBMR), Gruppe Neurologie, Universität Bern, und Universitätsklinik für Neurologie, Inselspital Bern. © zvg
Dr. Mattia Aime, Department for BioMedical Research (DBMR), Neurology, University of Bern, and Department of Neurology, Inselspital, University Hospital Bern © Courtesy of Mattia Aime
Mattia Aime, how are emotions linked to sleep?

Emotions are essential for our survival. For example, in nature, animals have to flee when they receive salient signals, and feel an emotion, in this case fear. So this is a sort of "tag" that allows animals to respond to salient information from the environment. And this information is stored as a memory in the brain. During sleep, the brain triages emotions to consolidate the storage of positive emotions while dampening the consolidation of negative ones. This process occurs preferentially during REM sleep, when there is increased brain activity. That's why we investigated the mechanisms that store information about emotions during REM sleep.

What exactly did you study?

Emotions derive essentially from one center in the brain, the amygdala. When processing information, the amygdala is also helped by the prefrontal cortex. Therefore, we studied this brain region. We discovered that blocking specific neurons in the frontal cortex, selectively during REM sleep, disrupts the processing of information associated with emotions experienced during the day.

What are the consequences of this?

When we blocked these neurons, that is, messed up with the sorting of information related to emotions, we generated a kind of post-traumatic stress disorder in mice. We suspect that this sorting is probably absent in patients who suffer from anxiety disorders, including post-traumatic stress disorder. They are unable to mitigate traumatic emotions during sleep and relive them over and over again. A kind of "emotion stasis" occurs at the level of cell bodies, which manifests itself in a persistent anxiety signal.

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Using a technique called optogenetics, the activity of cells in the brain can be artificially modulated with light pulses © Pascal Gugler / Insel Gruppe
What, then, would be a possible therapeutic approach?

In 10 years, there will probably be new techniques that will make it possible to target specific populations of neurons in a particular brain region. In our work, we identified such targets in mice. Certain techniques, such as deep brain stimulation, are already able today to stimulate subpopulations of neurons in the brain. But with the rapid advances in neuroscience, I think in 10 years we'll be able to selectively target the neurons we've described, pharmacologically or otherwise.

You are working with mice. Is it necessary to do animal studies for this kind of research, or could it be done using modeling?

Modeling is a consequence of what we do with animal research. In order to develop a model, we need basic data from real animal experiments. Unfortunately, we can't do it today without animal experiments. Also, we have to conduct our experiments in vivo, that is, in living animals, because sleep cannot be obtained in a brain slice or in vitro.

What fascinates you about sleep?

We have to sleep at least a third of our day, but we still don't know exactly why. We are discovering more and more new functions of sleep, but why we really need to spend so many hours sleeping remains unclear - and why and how exactly it is coupled with emotions. Such mysteries are always something fascinating for humans!

And why did you specialize in emotions?

I think everyone is interested by emotions. We feel and experience them every day, but we are currently not sure what the function of these emotions is, why we feel a variety of emotions throughout the day. That's what I'm interested in, and in my PhD thesis, I identified a region in the prefrontal cortex that stores and reorganizes information in response to an emotional event. I came to the University of Bern to join the lab of Antoine Adamantidis, who studies brain mechanisms of sleep and wake cycles, because I was convinced that this sorting occurs during sleep. In fact, we were able to show that this sorting, which I had described in my thesis, takes place during the REM phase. So REM sleep seems to be an important window for storing emotional information and helping to discriminate between positive and negative emotions.

The amgygdala (red) - together with other brain regions - controls our mental and physical reactions to stressful and anxiety-provoking situations © Life Science Databases / Wikicommons (CC BY-SA 2.1 JP)
What is your next project?

In the future, I’m looking for a group leader position. On a scientific level, I would like to further investigate the link between emotions and sleep, particularly REM sleep. I would like to find out what the amygdala, as the core of emotional processing, is doing during sleep. Currently, there is very little knowledge about what role the amygdala plays in organizing and storing information during sleep.

Do you actually get enough sleep?

Actually, we sleep researchers live a bit inconsistently because we know about the importance of sleep, yet we spend so many hours in the lab (laughs). But since I've been doing research on this topic, I've become more aware of how important sleep is and try to get at least eight hours a day. I also think that our findings from the lab make people aware of how important sleep is - for example, by showing that disrupted sleep not only leads to emotionally induced anxiety disorders, but also diseases like depression, which not only cause a lot of suffering, but also high healthcare costs. So research in this area can have a big impact on society.

PFIZER RESEARCH AWARD

For over 30 years, the Pfizer Research Prize Foundation has honored outstanding findings in biomedicine. In each of the following disciplines, work from basic and/or clinical research is honored: Pediatrics - Cardiovascular, Urology and Nephrology - Infectiology, Rheumatology and Immunology - Neuroscience and Diseases of the Nervous System - Oncology.

The prize money per paper amounts to 15,000 Swiss francs. In total, the foundation has thus supported biomedical research in Switzerland with more than 6.5 million Swiss francs to date. The award ceremony of the Pfizer Prizes 2023 will take place today. A prize will also be awarded to Dr. Amanda Gisler and team from the University Children's Hospital Basel and Inselspital, University Hospital Bern.

SLEEP RESEARCH AT THE UNIVERSITY OF BERN

Sleep research is a focus of the University of Bern and Inselspital Bern, including the Interfaculty Research Cooperation (IRC) "Decoding Sleep". It is an interdisciplinary project funded by the University of Bern, which started in 2018. It is comprised of 13 research groups from the Faculty of Science, Medicine and Human Sciences and bridges several domains including Medicine, Psychology, Psychiatry and Computer Science. The project aims to gain new and in-depth understanding of the function and regulation of sleep-wake-rhythms and to develop strategies for early and personalized therapies of sleep-wake and neuropsychiatric disorders. Among the numerous research successes from the Bernese consortium, reports which highlighted that people can learn new vocabulary of a foreign language during deep sleep and that in animal models, recovery after a stroke can be promoted by influencing sleep, gained a lot of media attention. 

About Mattia Aime

Mattia Aime is a postdoctoral researcher at the Department for BioMedical Research (DBMR), Neurology Group, University of Bern and University Hospital of Neurology, Inselspital Bern.

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