Coordinated brainstem slow waves may determine when it's time for REM sleep

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by Ingrid Fadelli, Medical Xpress

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edited by Sadie Harley, reviewed by Robert Egan

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Example recording session, including hypnogram, normalized EEG spectrogram, EMG amplitude and heat map representing the firing rates of 185 simultaneously recorded neurons. Each row shows the activity of one neuron (its firing rate) throughout sleep. The columns are the different time points. The map shows how about ~200 neurons are simultaneously changing their activity throughout sleep. One can see how most, but not all become activated during REM sleep and how their activity fluctuates during NREM sleep on a minute time scale. Credit: Lozano et al. (Nature Neuroscience, 2026).

Sleep is one of the most widely studied states of consciousness, known to play a role in physical recovery, the processing of memories and the regulation of immune functions. During sleep, the brain transitions between light sleep, intermediate sleep, deep sleep and dreaming.

These phases can be divided into two main stages, called non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep. During REM sleep, the phase of sleep associated with dreaming, researchers have recorded both rapid eye movements and an increase in brain activity.

Past neuroscience studies linked the emergence of REM sleep with structures in the brainstem, the stalk-like structure connecting the brain to the spinal cord. However, the neural mechanisms that regulate the transition from NREM to REM sleep have remained poorly understood.

Researchers at the University of Pennsylvania and the Champalimaud Foundation monitored the mouse brain during sleep to better understand how the brainstem coordinates the shift from NREM to REM sleep. The results of their study, published in Nature Neuroscience, suggest that this transition is preceded by distinctive slow fluctuations in the activity of brainstem neurons, which appear to determine when animals enter REM sleep.

"The study came from a long-standing question in the sleep field: How does the brain decide when to enter REM sleep?" Franz Weber, senior author of the paper, told Medical Xpress.

"REM sleep is a very distinct brain state, but it does not occur completely randomly. It is typically preceded by a period of non-REM sleep, and somehow the brain must determine when the time is right to transition into REM sleep. Historically, REM sleep has often been studied by focusing on specific brain areas or specific cell types that can promote or suppress REM sleep.

"While this has been extremely important, we wanted to take a broader view and ask whether REM sleep might also be controlled by coordinated activity across larger brainstem networks."

Tracking brainstem activity during sleep

Weber and his colleagues wanted to better understand how the activity of different populations of neurons in the brainstem changes before the onset of REM sleep. Their hope was to shed light on why REM sleep occurs at specific moments instead of others.

As part of their experiments, they simultaneously recorded the activity of hundreds of neurons in the brainstem of mice while they were asleep. They collected these recordings using high-density Neuropixels probes, tiny devices developed by a large research group at the Howard Hughes Medical Institute, University College London (UCL), the Allen Institute for Brain Science and other institutes.

"These probes allowed us to observe how large populations of neurons change their activity as the brain moves between wakefulness, non-REM sleep and REM sleep," Weber explained.

"We then used computational approaches to identify the dominant patterns in this population activity. In simple terms, instead of looking only at one neuron at a time, we asked whether there are coordinated activity patterns across many neurons that collectively push the brain toward REM sleep."

The researchers observed that while the mice were asleep, activity in their brainstem appeared to be organized in two broad patterns that affected various neuron populations. During NREM sleep, they observed slow waves of population-wide activity gradually building up before REM sleep began.

"Notably, these dynamics could predict when the brain was more likely to enter REM sleep," Weber said. "We also combined these recordings with optogenetic experiments, in which we stimulated specific REM-promoting neurons in the brainstem and cortex. This allowed us to test whether the ongoing network state of the brainstem influences whether such stimulation successfully triggers REM sleep or not."

The researchers identified two different groups of neurons, which were active and inhibited during REM sleep, respectively. These neuron populations also exhibited opposite activity patterns (i.e., increases and decreases in activity) between REM sleep episodes.

Implications for the understanding of dream sleep

The results of this study suggest that REM sleep is not controlled by a single neural "switch." Instead, it appears to emerge from the coordinated activity of large populations of neurons in the brainstem.

"Our data suggest that REM sleep emerges from coordinated activity across a distributed brainstem network," Weber explained. "We identified slow population dynamics that gradually prepare the brain for REM sleep and predict when REM sleep will occur. This changes how we think about REM sleep regulation.

"Rather than asking only which specific area turns REM sleep on, we also need to understand the network state that allows REM sleep to emerge."

In the future, the team's observations could help researchers understand the processes underpinning disruptions in REM sleep associated with various neurological and psychiatric disorders. This may, in turn, pave the way for the development of strategies to modulate sleep states.

Meanwhile, Weber and his colleagues plan to continue exploring the brainstem network dynamics they observed. As part of their next studies, they would like to better understand the processes underpinning their generation.

"We want to know which specific cell types and circuit interactions give rise to the slow population dynamics that prepare the brain for REM sleep," Weber added.

"We are also interested in how these dynamics relate to the function of REM sleep. REM sleep has been linked to dreaming, emotional processing, memory and brain development, but its core functions are still not fully understood. If REM sleep is an emergent network state, rather than the output of a simple switch, this may provide a new way to study what REM sleep is doing for the brain."

Written for you by our author Ingrid Fadelli, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Publication details

David E. Lozano et al, Low-dimensional population dynamics in the brainstem gate REM sleep, Nature Neuroscience (2026). DOI: 10.1038/s41593-026-02314-z.

Journal information: Nature Neuroscience

Key medical concepts

Sleep, REMBrain StemOptogenetics

Clinical categories

Sleep medicineNeurologySleep & Recovery Who's behind this story?

Ingrid Fadelli

Freelance journalist with BSc Psychology and MA International Journalism. Covers AI, robotics, neuroscience, and astrophysics since 2018. Full profile →

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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