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Highlights

• Forced loss lowers social ranks and induces depressive-like behaviors
• Forced loss generates negative reward prediction error
• Forced loss but not natural loss activates LH-LHb circuit and induces LHb bursting
• LHb burst firing inhibits mPFC and reinforces subordination

Summary

Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce depressive-like behaviors. These rank-decline-associated depressive-like behaviors can be reversed by regaining social status. In vivo fiber photometry and single-unit electrophysiological recording show that forced loss, but not natural loss, generates negative reward prediction error (RPE). Through the lateral hypothalamus, the RPE strongly activates the brain’s anti-reward center, the lateral habenula (LHb). LHb activation inhibits the medial prefrontal cortex (mPFC) that controls social competitiveness and reinforces retreats in contests. These results reveal the core neural mechanisms mutually promoting social status loss and depressive behaviors. The intertwined neuronal signaling controlling mPFC and LHb activities provides a mechanistic foundation for the crosstalk between social mobility and psychological disorder, unveiling a promising target for intervention.

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So, if I like power and you take away my power I’ll be depressed? Sounds about right.

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Everybody should be in here for the figure. It’s a ready-made meme.

How did they do this? Forcing mice to play EA sports games?

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I think making any living creature lose something will probably have an effect, kind of obvious really.

Not gonna lie, some of these experiments don’t seem to have any purpose.

Why does the image relate to Ketamine ?

This is absolutely fascinating, thank for you sharing. Very relevant to the fields I work in, and I haven't been familiar as much with Dr. Hu's work as I apparently should be.

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Figuring out chemical factors in the brain, especially pertaining to mental health, is invaluable to helping people with mental illness.

You're only looking at the simplified underlying results of the test, not the scientific goals. They can determine the areas of the brain affected and ways to combat it. Chemicals needed, so more research into drugs could be gleaned from this.

If you can observe it objectively in humans, why do you need to do it to mice? Like just leave the mice alone.

“When you're accustomed to privilege, equality feels like oppression"

The happy little mouse king is so cute

Oh I’m the mouse here.

Sad deposed mouse is sad. If anything sad mouse will become a reddit meme.

Are you a mouse?

You'd have to sack people just before Christmas to get the same effect. There'd be an outcry!

I eat a lot of cheese... so maybe...

I suppose so, but I feel like there are better ways to do this nowadays than animal testing.

Unfortunately, there isn't. Computer modelling just isn't there. Not to mention, getting natural physical reactions is impossible to model in any form other than observing live specimens in real time.

It's unfortunate. However necessary, unless you're willing to expend human lives to advance research.

We literally have countless depressed humans on earth visiting psychiatrists. All it would take is to give them a brain scan and voila, we have a much better result than this.

And if we’re worried about privacy? Just ask their permission or give a monetary reward. There are bound to be some people willing to help science.

That's not quite the process... also, you want to exploit people?

The thing about the testing (especially brain testing) is that it's super invasive, many times involving the death of the subject in order to visually see the brain or take samples. Drug testing results in debilitating conditions or death.

Subjecting humans to this would be horrible. Having "depressed people", or "prisoners", or any other human you suggest would be far more ethically and morally bankrupt than testing on the mice.

I think all life is valuable. However, mice reproduce very quickly, they live short lives, they are small one have traits that make them good for observing because they are close to humans, and they are also well... animals.

Humans have an innate need to discover things. Doing it this way is surprisingly the lesser of two evils. No matter what you think of medical animal testing, you've reaped its benefits at some point in your life.

If it makes you feel any better, the scientists are very nice to them.

If it can’t be done with compassion I still don’t see the point.

There are already medications for depression, torturing mice isn’t going to teach us anything we can’t already fix or don’t already know.

Well, as this article explains, it can and does.

But if you just have someone doing any competition compete vs some pro at that competition. Not sure how well that works on everyone. If failure was inevitable then that can be used to rationalize the loss, making it invalid, thus reducing the depressive state.

Also isn't it the case with for example gangs that they are hyper aggressive when there is no clear social mobility. Some individuals become hostile over depressed. I suppose depression follows after tho when there is 0 gain