Stress and sleep

TLDR: Neurons in the midbrain respond to social stress by causing sleep and inhibiting stress hormone production.

Big Takeaways

  1. Social stress causes mice to sleep more.

  2. Sleep reduces corticosterone (mouse cortisol) levels.

  3. VTAVgat neurons decrease corticosterone production.

  4. Both sleep and functional VTAVgat neurons are needed for reduced stress.

  5. Stressed out? Ignore it! Sleep!

The Problem

Ever go to sleep stressed, wake up feeling great, and realize what you were stressed about is no big deal? If so, it isn’t a coincidence. According to this study, it’s possible that specific neurons in your brain work to reduce your stress levels while you sleep.

At this point, you’ve probably heard that chronic stress is bad for you. A little stress can be helpful, but if you stay stressed out for long it has some nasty effects. Sleep is one of your body’s ways of returning your stress to normal so it doesn’t become a chronic issue.

But how?

stress → ??? → sleep → ??? → lower stress

The Solution

The authors of this week’s paper tried to figure it out.

To start, they caused mice to feel some social stress by placing a new mouse in their cage. This social stress caused them to promptly fall asleep when it was over, while physical stress (aka running on a treadmill) didn’t.

I agree with the mice, being social is much more tiring.

However, the mice didn’t just sleep more, their stress levels actively went down and they woke up no longer acting anxious. Corticosterone (CORT), the mouse version of cortisol, is a key hormone that dictates stress. Social stress caused the mice’s CORT levels to jump up but sleep brought it back down.

So far:

social stress → ??? → sleep → ??? → lower CORT → lower stress.

But why? That’s the ever-present question about sleep. It works, but why?

Neuroscientifically Challenged

Lucky for us, the authors also wanted to know.

They stressed out the mice and then observed what areas of the brain responded by looking at a neuron activation marker, cFOS.

The ventral tegmental area (VTA) lit up with activity (blue dot in the image). It helps regulate both stress and sleep, so naturally, they decided to focus on it.

In the VTA, 60% of the neurons that responded to stress had the marker Vgat. These VTAVgat neurons also happen to cause sleep. What a coincidence!

social stress → VTAVgat → sleep → ??? → lower CORT → lower stress

To wrap it up, the authors made some of these VTAVgat neurons glow and watched where they went. The neurons expressed a fluorescent protein called mCherry (yes, it’s red) and extended into a region of the brain largely responsible for starting the stress response.

Once there, the neurons prevented cells from making a protein responsible for CORT levels, causing them to go down.

Flow chart solved!

social stress → VTAVgat → sleep + inhibiting PVN → lower CORT → lower stress

You might be wondering, why does any of this require sleep? Couldn’t we just take a pill that lowers CORT and call it a day? The answer: no.

The authors tried. A lot. It didn’t work.

The mice needed both functional VTAVgat  cells and sleep to have their CORT levels and anxiety reduced. One or the other didn’t do them any good.

But why!? What does sleep do!?

Unfortunately, not sure. Sleep is still a mystery, per usual.

See you next week for more science,

Neil

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