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Recent discoveries about the Arc protein have shown that its function and origin may be even more complicated than scientists originally thought.

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[INTRO ♪].

We've all learned that neurons are one of the main building blocks of your brain. They shuttle along information so you can think and feel and remember and do things.

Neurons communicate with each other using chemicals called neurotransmitters, which get passed through a gap called a synaptic cleft. Now, this way of communication has been the basis for a lot of research into brain chemistry, and it has massively influenced how we design medicines that target the brain. But scientists have observed a new way that neurons can pass information.

It's pretty groundbreaking… and it's pretty weird. All this excitement centers around the Arc gene. Like many genes, it encodes a string of mRNA which encodes a protein.

And Arc has been studied in relation to memory and learning. After a neuron fires, which is when an electrical signal gets sent through the cell, the Arc protein and mRNA build up in the cell's dendrites. These are the branches that connect one neuron to others, usually by receiving neurotransmitters.

Arc's full name is activity-regulated cytoskeleton-associated protein, because it's involved in changing a neuron's cytoskeleton— the network of proteins that gives cells their structure. We think this helps reinforce connections between neurons, which helps us hold on to information. Stronger connections mean stronger memories.

And without the Arc gene, we might not be able to remember new things as easily. In a study from 2000, researchers conducted some experiments involving the Arc gene in rats. They used 42 male rats, half of which were dosed with a compound that messed with Arc mRNA and kept them from making proteins.

The other half got a control dose that didn't affect Arc. After the brain treatment, the rats were trained to find a hidden platform in a tank filled with water. All the rats did fine after a couple practice rounds, Arc protein or not.

But then, 48 hours later, they were all tested on their ability to find the platform again. And rats that had the Arc-inhibiting dose in their brains did worse than the control group, which the researchers took to mean that they had trouble forming memories of the practice. In a separate experiment, they tried dosing rats with the compounds 8 hours after the training session.

And both groups of rats did about the same on the test! So this makes Arc seem especially important while the rats were learning the task and forming those neural pathways. Now, this bit of research in itself is neat.

But Arc is also interesting in human brains, even though we're not entirely sure what it's doing. Abnormal levels of Arc protein have been found in patients with Alzheimer's disease. And studies with genetic analyses have suggested that.

Arc gene variants may play a role in schizophrenia. And then there's the Arc research that's changing how scientists think about brains altogether. In a paper published in January 2018 in the journal Cell, researchers from the University of Utah described their most recent work on the Arc gene— when things took an unexpected turn.

The first big surprise was when they looked at some engineered bacteria that were churning out Arc proteins from a rat gene. They noticed that Arc was clumping up into structures that looked weirdly like capsids— tiny protein capsules that protect the genetic information of viruses. Not only that, but more tests showed that Arc capsids form little packages around Arc mRNA and other RNA that might be hanging out in cells.

Which is also like viruses. Then, the scientists tried sticking the Arc proteins in a bunch of mouse neurons and noticed that capsids were actually shuttling mRNA between cells. And with the extra mRNA, the receiving neurons could probably generate even more Arc.

That's what had researchers floored:. Arc capsids crossed synapses. They carried information between neurons in a way that we thought was exclusive to neurotransmitters!

And after some genetic analyses, they think that the Arc gene doesn't just act like a virus…. Hundreds of millions of years ago, it probably came from a retrovirus ancestor that infected our ancestors and got into our genome. Now, having virus genes stick around in your body might sound a little risky—I mean, that's the huge problem with HIV.

But some estimates suggest that up to 8% of human DNA could've come from retroviruses. Most of this DNA has changed enough that it doesn't do anything. But some researchers have argued that certain viral fragments have been repurposed by our bodies.

And now with Arc, we aren't sure how or why our neurons seem to be using these virus-like capsids. Not to mention, they're not just in the brain. In a separate paper published on the same day in the same journal, researchers from the University of Massachusetts reported on Arc capsids crossing synapses in fruit flies.

But in these experiments they were crossing the neuromuscular junction— where neurons and muscles meet. So it seems like Arc could be involved in connections here, too. Not just between neurons.

All these findings are still really new, so scientists have a lot more questions than answers. We still don't really know how this virus-like communication strategy affects memory, or even what else could be ferried around by Arc capsids. Like, what if they help toxic proteins move around the brain, which is a major problem with Alzheimer's disease.

So first, researchers studying Arc want to try and repeat these observations. And then they'll keep experimenting, looking in mammals instead of isolated cells or flies to try and find these Arc capsids in action. Some scientists think this could open up a new door in treating brain-related illnesses in humans.

Instead of drugs that target neurotransmitters, someday we may be able to use Arc capsids to smuggle helpful stuff directly into neurons—and that would be pretty revolutionary. Thanks for watching this episode of SciShow Psych! And if you want to learn more about memory, you can check out our other videos on this channel, like one where we explain whether photographic memory really exists. [OUTRO ♪].