Sleep induced by stress can help mice cope with later fears

Overview: Research reveals how stress can trigger sleep in mice, and how this stress-induced sleep can help reduce anxiety the next day.

Source: Imperial College London

Stress stimulates a type of sleep in mice that then relieves anxiety, according to new research that also pinpoints the mechanism.

Because sleep is similar in mammals, the same mechanism is likely activated in human brains. Uncovering the mechanism could lead to artificial ways to amplify its effects, thereby treating persistent stress disorders such as PTSD.

We often think of stress that keeps us up at night, but certain types of stress seem to induce sleep. Now, a study led by researchers from Imperial College London and institutions in China has discovered how this happens in the brains of mice.

Not only did they find out how sleep is generated, but they also reported that the sleep the mice experience the next day appears to lower their anxiety levels. The findings are reported today in the journal Science

There are two main types of sleep that we, and all mammals, experience: REM (rapid eye movement, where we tend to dream) and non-REM (NREM; deeper, dreamless sleep). People who suffer from PTSD experience less REM sleep, which contributes to the theory that REM sleep helps us process difficult emotions and stress.

Lead researcher Professor Bill Wisden, of Imperial’s Division of Life Sciences, said: “Our results reinforce the idea that REM sleep helps us cope with stress. However, we previously only knew how REM sleep is reduced, like some drugs that suppress these.

“Now our study has revealed a mechanism by which REM sleep is induced, paving the way for drugs or other interventions that target the right neurons and amplify the stress-reducing power of sleep.”

The researchers induced a type of psychosocial stress in mice called “social defeat,” which is used as an analog for human bullying. Mice were exposed to particularly aggressive mice (without physical damage), after which researchers found that flight or fight hormones rose in their blood, indicating stress.

Then, when the mice slept, researchers monitored the activity of their neurons (brain cells). This revealed a specific set of neurons that detected and responded to the stress hormone levels and that induced high sleep in both NREM and REM.

The activity of these neurons and levels of NREM and REM sleep remained high for about five hours of sleep, also sending signals to other neurons that regulate stress hormones, preventing them from releasing more.

Circuits in the brain can induce restorative sleep that protects against further anxiety. Credit: Imperial College London

So the newly discovered neurons not only detected stress and thereby induce sleep, they also caused the reduction of stress hormones.

When the mice woke up, the researchers tested their fear response to see how sleep affected their stress behavior. They did this by measuring how long the mice spent in the light, rather than seeking out the darkness, because they do more when they’re anxious.

Their responses were compared to stressed mice that were either lacking sleep (stimulated with objects) or whose newly identified neurons were impaired, meaning they were not getting the restorative sleep that normal mice got.

The mice that didn’t get their stress-induced sleep spent much more time in the dark, indicating they were more anxious and their stress hormone levels remained high.

Now that this new mechanism has been found, the team now hopes to find ways to selectively attack the neurons responsible to enhance their positive effects through sleep.

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The team was funded by the Wellcome Trust and the UK Dementia Research Institute. Being diagnosed with dementia can cause significant psychological stress, and the team hopes that if their research can lead to a way to amplify the effects of sleep, it will help people cope with a new diagnosis. People with dementia also have more emotional disturbances, and stimulating REM sleep can also help reduce this distress.

About this sleep and psychology research news

Author: Hayley Dunning
Source: Imperial College London
Contact: Hayley Dunning – Imperial College London
Image: The image is attributed to Imperial College London

Original research: Closed access.
“A specific circuit in the midbrain senses stress and induces restorative sleep” by Bill Wisden et al. Science


Abstract

A specific circuit in the midbrain senses stress and induces restorative sleep

In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep may enable resilience, but how stress promotes sleep is unclear.

Activity-dependent tagging revealed a subset of the ventral tegmental area -aminobutyric acid (GABA)-somatostatin (VTA)Vgat-Sst) cells that detect stress and direct non-rapid eye movements (NREM) and REM sleep through the lateral hypothalamus and also inhibit the release of corticotropin-releasing factor (CRF) in the paraventricular hypothalamus.

Transient stress increases the activity of VTAVgat-Sst cells for several hours, allowing them to sustain their sleep effects. Lesion of VTAVgat-Sst cells abolished SDS-induced sleep; without this, anxiety and corticosterone concentrations remained elevated after stress. For example, a specific circuit allows animals to restore mental and bodily functions through sleep, potentially providing a sophisticated pathway for treating anxiety disorders.

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