scishow psych
Remote Control Brain Receptors
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Duration: | 08:02 |
Uploaded: | 2021-08-24 |
Last sync: | 2024-10-28 13:00 |
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!
This video was sponsored by Skillshare. The first 1000 people who click the link will get a free trial of Skillshare Premium: https://skl.sh/scishowpsych08211
Hosted by: Hank Green
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Sources:
https://www.pnas.org/content/104/12/5163
https://pubmed.ncbi.nlm.nih.gov/24525710/
https://pubmed.ncbi.nlm.nih.gov/22442487/
https://pubmed.ncbi.nlm.nih.gov/31900153/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759656/
https://pubmed.ncbi.nlm.nih.gov/29673525/
https://www.ncbi.nlm.nih.gov/books/NBK539894/
Images:
https://www.istockphoto.com/photo/active-nerve-cell-synapses-3d-illustration-gm1249958309-364406032
https://commons.wikimedia.org/wiki/File:Neurotransmitters.jpg
https://www.istockphoto.com/photo/catch-it-son-gm1316624887-404306679
https://commons.wikimedia.org/wiki/File:SynapseSchematic_unlabeled.svg
https://www.istockphoto.com/photo/synapse-gm492265695-40137814
https://www.istockphoto.com/vector/manipulative-relationships-young-female-character-being-manipulated-by-a-remote-gm1191993893-338512729
https://www.istockphoto.com/photo/abstract-3d-image-neural-cells-gm1277207386-376490342
https://commons.wikimedia.org/wiki/File:Clozapine_N-oxide.png
https://www.istockphoto.com/photo/cute-laboratory-rat-of-the-dumbo-breed-gm1019889316-274049047
https://www.storyblocks.com/video/stock/brain-neuron-also-known-as-a-neurone-or-nerve-cell-sbqsduq_dkgpo5mqk
https://www.storyblocks.com/video/stock/lab-mouse-albino-walking-off-screen-hwc0thmlxixsje07i
https://www.storyblocks.com/video/stock/calm-landscape-with-orange-sunrise-over-the-sea-slow-motion-rhf_bxe3mmjjqke2vw
https://commons.wikimedia.org/wiki/File:Prefrontal_cortex_(left)_animation.gif
https://www.eurekalert.org/multimedia/680024
This video was sponsored by Skillshare. The first 1000 people who click the link will get a free trial of Skillshare Premium: https://skl.sh/scishowpsych08211
Hosted by: Hank Green
----------
Support SciShow Psych by becoming a patron on Patreon: https://www.patreon.com/SciShowPsych
SciShow has a spinoff podcast! It's called SciShow Tangents. Check it out at https://www.scishowtangents.org
----------
Become a Patron and have your name featured in the description of every SciShow Psych episode! https://www.patreon.com/SciShowPsych
----------
Looking for SciShow elsewhere on the internet?
Facebook: http://www.facebook.com/scishow
Twitter: http://www.twitter.com/scishow
Tumblr: http://scishow.tumblr.com
Instagram: http://instagram.com/thescishow
----------
Sources:
https://www.pnas.org/content/104/12/5163
https://pubmed.ncbi.nlm.nih.gov/24525710/
https://pubmed.ncbi.nlm.nih.gov/22442487/
https://pubmed.ncbi.nlm.nih.gov/31900153/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759656/
https://pubmed.ncbi.nlm.nih.gov/29673525/
https://www.ncbi.nlm.nih.gov/books/NBK539894/
Images:
https://www.istockphoto.com/photo/active-nerve-cell-synapses-3d-illustration-gm1249958309-364406032
https://commons.wikimedia.org/wiki/File:Neurotransmitters.jpg
https://www.istockphoto.com/photo/catch-it-son-gm1316624887-404306679
https://commons.wikimedia.org/wiki/File:SynapseSchematic_unlabeled.svg
https://www.istockphoto.com/photo/synapse-gm492265695-40137814
https://www.istockphoto.com/vector/manipulative-relationships-young-female-character-being-manipulated-by-a-remote-gm1191993893-338512729
https://www.istockphoto.com/photo/abstract-3d-image-neural-cells-gm1277207386-376490342
https://commons.wikimedia.org/wiki/File:Clozapine_N-oxide.png
https://www.istockphoto.com/photo/cute-laboratory-rat-of-the-dumbo-breed-gm1019889316-274049047
https://www.storyblocks.com/video/stock/brain-neuron-also-known-as-a-neurone-or-nerve-cell-sbqsduq_dkgpo5mqk
https://www.storyblocks.com/video/stock/lab-mouse-albino-walking-off-screen-hwc0thmlxixsje07i
https://www.storyblocks.com/video/stock/calm-landscape-with-orange-sunrise-over-the-sea-slow-motion-rhf_bxe3mmjjqke2vw
https://commons.wikimedia.org/wiki/File:Prefrontal_cortex_(left)_animation.gif
https://www.eurekalert.org/multimedia/680024
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].
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].