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Disruptions in sleep quality or quantity, including REM sleep, are often associated with and precede the onset of nearly all affective psychiatric and mood disorders. Antoine Adamantidis is professor of neurophysiology systems at the University of Bern and director of the Center for Experimental Neurology (ZEN) at the University Hospital, Bern. At the 38th ECNP Congress in Amsterdam this year, he will give a plenary lecture summarising his group’s investigations into the cellular and circuit mechanisms underlying sleep architecture, sleep oscillations, and local brain dynamics across sleep-wake states. He recently spoke to Tom Parkhill, ECNP Press Officer, about his research.
Tom Parkill: I’ve been looking at your biography – you have moved around quite a bit. Are you French originally?
Antoine Adamantidis: I'm Belgian. I was born in France, but I grew up in Belgium and I have Belgian citizenship. I did my degree and PhD in Belgium and then I moved to California to Stanford University for my postdoc.
What did you do at Stanford?
I was amongst the very first to implement in vivo optogenetics in mice – amongst the very first to use this new technology, dissecting neural circuits controlling sleep and wakefulness in the mouse brain.
What led you to this?
It was pure serendipity. I joined the lab of my mentor Luis de Lecea when he was moving to Stanford. This was at the time when Karl’s group – Karl Diesseroth – had just published the first paper on in vitro optogenetics and I thought that that was the perfect tool I needed to try to understand how cells in the hypothalamus induce REM sleep, dream states. So, I wrote to Karl and he said, well, let's meet when you get here. And they were enthusiastic about it. So we started work and expanded it in many directions, working alongside various colleagues.
It must have been a very exciting time.
Yes, it was. It was really exceptional. A fantastic time, made even better by being in California.
So how long were you there?
Almost five years between 2006 and 2010. And then I joined McGill University in Montreal as a tenure-track assistant professor where I started my first lab. We focused our research on understanding the brain mechanism of sleep using optogenetics combined with electrophysiology. I stayed there for four years and then I was recruited by the University of Bern in Switzerland in 2014.
Was it a difficult change, moving back from North America back into Europe?
It was a gradual change. It was a bigger change moving from Belgium to California, that was quite a jump, but I enjoyed every bit of it. And then the move to Montreal was nice because culturally Canada is really in between America and Europe. And now I’m in Switzerland, so almost in Europe.
What’s your research in Bern?
We're still running some projects on the brain mechanism of sleep. But we got more and more interested in the mechanism of sleep oscillations and what they do in terms of brain function associated with sleep and in particular synaptic plasticity and memory consolidation, for example. And lately we’ve gone one step further and longitudinally tracked the activity of single cells, or even subcellular compartments such as dendrites or axons, across sleep-wake states using calcium imaging in sleeping mice. So we’re trying to make sense of brain activity at single cell resolution during sleep, to understand what’s happening in the brain during light sleep, deep sleep, dream states. The most significant discovery we’ve made recently is that sleep basically provides an update of information acquired during the day. Our model suggests that this updating is key to optimise brain and body physiology and ultimately behaviour in preparation for future challenges. That’s how we see it.
So if you don't sleep, then you don't have the resilience.
Exactly. We can survive a night without sleep, that’s no problem. We can survive quite long periods of time with chronic sleep perturbation, with sleep restriction, sleep fragmentation or poor sleep quality. But eventually this limits our ability to function in an optimal way, meaning that our response to our environment, our ability to learn, to adapt, to remember, to learn from past mistakes is strongly impacted by a change in quality, or quantity, of sleep. This is, of course, true for humans and animals in general. Imagine in the wild if an animal were unable to precisely locate where food was, or to understand which predator was dangerous. This becomes quite dangerous for the survival of the organism and eventually of the species. So I think overall sleep helps us to adapt to our niche.
Is sleep only mammalian?
Well, that's what we used to think, right? Because we used electroencephalography to record brain activity and classify different states of sleep or wakefulness. But with new techniques and studies in different animal species, it turns out that there are sleep states in almost all organisms, they just may not look like sleep states as we know them in humans. But they share very interesting similarities. For instance, octopuses, spiders, lizards, fish, worms all show sleep-like activity. And some of those species even show different states of sleep. Whether these are similar to light sleep, non-rapid eye movement sleep, or rapid eye movement sleep as we know them in human and mammals in general is still something under debate.
So my take on this is that there are different sleep states, we are just not able to characterise them fully, to understand how they manifest themselves in those species in comparison to what we know about humans.
So it seems to be a very basic evolutionary development?
Yes it is.
About possible evolutionary advantages to sleep, in the past some said that being inactive meant that you were less vulnerable to predators, but you are saying that sleep is really a processing development.
That’s one aspect, but I think there are also many other brain and body functions that are associated with sleep that include, for instance, brain clearance. There has been a lot of ongoing debate recently on how sleep might support brain clearance of metabolites which have been produced during wakefulness. There is obviously an energy conservation aspect; energy allocation differs between sleep and wakefulness. And then there are very specific states of sleep either during development or as a result of lifestyle that may involve different functions. So, for example, human babies or animal pups show very different sleep cycles to those found in adults. So, one of the models is that this deep sleep provides a window for brain maturation during development. Environmental conditions represent another constraint on sleep, such as an abundance of sleep – hibernation, for example – or a real scarcity of sleep, such as during migration, which can result in an adaptation to sleep over land instead of at sea or in the air, although marine mammals have uni-hemispheric sleep and some birds may have developed the ability to adapt their sleep to long migration times. How does that work? It's not yet completely understood, but it shows one interesting thing: that sleep is extremely plastic and can be adapted not only to the needs of the body, but also those of the environment.
How did you get involved with the ECNP?
That’s a good question! I think one reason is we recently published a paper that showed that REM sleep is involved in emotion regulation, and that very subtle imbalances in the function of single cell activity in part of the prefrontal cortex during REM sleep, during dreaming, have profound consequences on discrimination between danger and safety.
That study built on decades of work implicating emotional memory with REM sleep and sleep in general. The mechanism we discovered could explain links between altered brain activity during REM sleep and psychiatric disorders, such as PTSD or stress disorder. Our model provides an experimental framework to test this new hypothesis. Such translational concept that bridge fundamental neuroscience to psychiatry are unique and I’m excited to share this at the upcoming ECNP Congress.
It's interesting that you're talking about sleep mechanisms being directly involved in certain mental health issues. I remember a few years ago when at one of the ECNP Congresses I did a press release on ADHD and sleep and it got very good press coverage. But, of course, some of the media didn’t really understand what the researcher was trying to say. This is, I suppose, one of the problems about actually dealing with a subject that everyone has an opinion on.
Well, it’s sometimes also difficult because the state of knowledge is simply not as advanced as in other fields. I think now there are many more links between sleep and ADHD, for instance, at least in humans, but not many in mice. New technologies such as calcium imaging give us a direct access to brain functioning – such technologies offer literally a window on the inner working of the brain – which means that scientists can see which cells are active, or not, when the mouse is sleeping, performing a task, or developing fear or aversion. Combine this with molecular profiling and optogenetic manipulation and it opens unprecedented translational research possibilities!
In this context, and in the media, there is increasing consciousness about the importance of sleep and how it can impact brain and body health.
If you had one thing that you would like to communicate to the ECNP audience, one message in the talk you’re giving, what would it be?
It’s probably the fact that, beside the importance of sleep in brain and body health, sleep is a window on how the brain works, and how it relates to mental health and brain disorders.
The centrality of sleep to mental health.
Yes, exactly. What the brain reveals during sleep not only offers insights into its functioning while awake but also underscores the vital role of sleep in maintaining mental health.
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