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We have a powerful way to study how brains work thanks to a relatively new technology called chemogenetics. With chemogenetics, scientists can give an injection to mice that turns specific parts of their brains on or off!

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This episode of SciShow Psych  is supported by Skillshare.

The first thousand people to  click the link in the description can get a free trial of  Skillshare’s Premium Membership. [♪ INTRO]. What if you could get a shot in the arm  and for the next few hours be able to turn on parts of your brain  that were inactive before?

What would you do with that power? Well, such things are already possible, in mice. All thanks to the relatively new  technology called chemogenetics.

And it’s giving scientists a powerful  way to study how the brain works, from memory to movement. Chemogenetics is a mixture of  chemistry, engineering, and genetics. It allows researchers to essentially  install a lock on certain neurons, and then administer the  metaphorical key whenever they want.

To do that, they add an artificial  receptor to an animal’s brain cells. They can then use that receptor to  activate or inactivate those cells by giving the animal an injection of  chemicals that bind to that receptor. Now you do not need to worry about  anyone controlling your brain with chemogenetics because this tool is only  being used in laboratory animals like mice.

But for now, the rodent experiments  are giving scientists a lot of insight into the inner workings of the brain. So, how does this all work? Well it starts with neurotransmitters,  chemicals that carry signals throughout your brain by  traveling from neuron to neuron.

You can picture it like  tossing a ball to your friend. And different neurons are equipped to  “catch” different neurotransmitters. So rather than playing catch with your friend, it is more like the two of you are standing  on the street surrounded by other people who are also sending other  kinds of balls back and forth.

You might be throwing a baseball to your friend, who’s wearing a catcher’s mitt and accepting  the baseball when it comes to them. But let’s say you accidentally throw  the baseball closer to another person standing in the street who’s holding  a hockey stick because their friend is sending them a hockey puck. They wouldn’t be equipped to catch the baseball.

And your friend with a  catcher’s mitt wouldn’t be ready to stop a hockey puck from soaring past. Ok, so you get it, right? The balls are neurotransmitters, and  the catcher’s mitt and hockey stick are receptors, or molecular tools  that receive specific chemicals.

Researchers can use this system to study what a cell does by turning  it on and off on demand. To do that, they can introduce a receptor that doesn’t have a  neurotransmitter associated with it. Like you put a soccer goal in the  street, but nobody has a soccer ball.

Are we stretching this one too thin? I don’t think so! I think it works!

So then they would be able to install  a lock and key system to turn cells on or off whenever they wanted to. If you control where the soccer goal  goes and when the soccer balls show up, you can make a remote control  system for your brain. And these custom receptors exist, and they have a very intimidating name: DREADDs.

It stands for Designer Receptors  Exclusively Activated by Designer Drugs. They are a form of chemogenetics that places  an artificial receptor, or soccer goal, into the brain so that the researchers can  introduce artificial neurotransmitters, or soccer balls, to attach to them and  change the way those brain cells behave. The receptors won’t be found  anywhere else in the body, and nothing in the body binds to them.

They only take effect when a scientist  also injects the specially designed drug. This is important because these DREADDs  were designed to add brain control. If scientists injected something into  the brain that ran amok binding to all sorts of unintended cells and  activating unwanted behavioral pathways, it would be out of control.

There would be way more side effects, potentially making it less safe for the animal. DREADDs can be introduced to mice either  by surgery or genetic engineering. The soccer ball for your new soccer goal will often be a drug called  clozapine-N-oxide, or CNO.

This technique debuted in a 2007 study. First, researchers conditioned a  mouse to be scared of a specific room. They shocked the mouse’s foot  when it entered the room, and it would respond by freezing in place.

Foot shocks produce a freezing response in mice that researchers can use  to tell if they’re scared. But when they turned off brain cells  in the hippocampus, or memory center, using inhibitory DREADDs, the mouse  didn’t show signs of fear anymore. Its freezing time was significantly decreased.

It was as if the mouse had  forgotten that this room was scary. Now, the point here is not to  create, like, fearless mice. Scientists use chemogenetics in rodents  to learn which areas of the brain are responsible for making memories by switching them off and observing that  they’ve kept memories from forming.

But they can also influence a mouse’s memories. In 2012, the same team of researchers  genetically engineered mice to express DREADDs only on  neurons that were active. Now, these mice were trained  in two different boxes: a relaxing one, and a scary one  where they got a mild foot shock.

The researchers basically set it up  so that the cells expressing DREADDs would be associated with memories  from the peaceful first box. So normally, mice would remember the  foot shock and freeze in box number two. But if they got a dose of  CNO, they wouldn’t freeze… like they were remembering box number one instead.

So the researchers were able  to activate a different memory than the one that would’ve otherwise  been triggered in a mouse’s brain. And these kinds of memory-manipulating experiments produce real behavioral outcomes,  like not freezing in fear. But this is not something we’re going  to be doing on humans any time soon.

There are definitely ethical limits  to the manipulations we will undertake with our own brains, and any  clinical applications down the road will have to be vetted very carefully. But there are some potential  ways chemogenetics could help us. For instance, imagine if we could do  something similar for patients with post-traumatic stress  disorder, helping them manage the fear they experience in  response to specific memories.

The patient could form a memory associated  with something positive or calm. Then, when they are in an environment  likely to trigger negative memories, they could theoretically activate the  cells associated with the peaceful memories to retrain their associations  and replace the old memories. And memory is just one of  its potential applications.

Like the brain does a lot more than that. DREADDs in the prefrontal cortex  could control attention, for example. The two most commonly used forms of chemogenetics are excitatory and inhibitory.

Scientists either excite cells  and make them more active or inhibit cells and make them less active. If they wanted to regulate attention, they  might apply inhibitory chemogenetics to the prefrontal cortex because  that part of the brain is involved in regulating attention behavior. Some people have more activity in  the prefrontal cortex than others, which can make more focused attention difficult.

Using DREADDs, they could theoretically  inhibit some of that prefrontal cortex activity and decrease the competing  signals in their prefrontal cortex to have an easier time focusing. Others might benefit from excitatory DREADDs to achieve their optimal attention state. Now we do have other methods of rewiring  neural circuits, such as optogenetics, which allows us to stimulate neurons with light.

But that’s invasive because  it usually requires hardware to be permanently affixed to the head. After a one-time surgery, rodents  recover fully from chemogenetic infusions and heal as if they’ve never had brain surgery. This technology would penetrate deeper  into the brain than optogenetics, and the effects would last  longer after stimulation.

In other words, chemogenetics might  lend itself to clinical application better than its cousins, although there’s  still a lot to learn before that could happen. Figuring out how scientists  would do that kind of thing using rodents is the first step. And in the meantime, we are learning a whole lot about how the brain works that  we could not learn before.

But for now, if you want to learn  more about how you can use your brain to learn new skills, you might enjoy Skillshare! Skillshare is an online  community full of resources where creative people can grow their skills. If you liked this video, you  might like Dr.

Andre Klapper’s class on How Your Memory Really Works. This class teaches the psychology of how  our brains remember and forget things. You can get access to this  and unlimited other classes with a Premium membership.

It’s curated specifically for  learning, meaning there are no ads, and they’re always launching new premium classes, so you can keep exploring new subjects. And if you’re one of the first 1,000 people  to click the link in the description, you will get a free one-month trial. Thank you for watching! [♪ OUTRO].