Lesion studies and experimental ablation

- [Voiceover] Ablation studies, or experimental ablation, describes the method of deliberately destroying brain tissue or making brain lesions, so a wound or an injury, in order to observe the changes that this might have on an animal's behavior. So for lesion studies, we're studying brain function by purposefully destroying parts of the brain and then studying the resulting change in behavior. And the main idea here is that the functions that can no longer be performed after the damage are the ones that were controlled by those damaged regions. And I know I've used a human brain to illustrate this, but I want to state right up front that this type of research is not done with humans. It is only done with lab animals, like rats or mice. There are number of different ways that experimental ablation can be performed. The first is surgical removal with a surgical scalpal, or similar instrument. So I have an image of a rat brain here, and scientists might remove this area in order to see what effect it will have on the animal's behavior. And while this can be done with a scalpal, it can also be done through surgical aspiration. And this involves literally sucking out brain tissue. But tissue removal is a little bit limited. Because you can really only use it for removing structures on the surface of the brain. Also, scientists aren't always interested in actually removing brain tissue. Instead, they're usually more interested in destroying the brain tissue in place, because usually this winds up being a lot less invasive. And that could involve simply severing the nerve with a scalpal. And when you do this, the signals that are being sent down that nerve can no longer reach their target area. And since that area can't receive any signals, it can no longer do the job that it was once doing. Another way is through radio frequency lesions. And this method, along with many of the other methods that we will mention, can be used to destroy tissue both on the surface of the brain as well as tissue that's deep inside of the brain. And to do this, a wire that is insulated except at the very tip is inserted into the brain to a pre-determined area. And I have an illustration of that here. So let's say that this wire has been inserted into a tumor that's right below the skin. Scientists will then pass a high-frequency current through the wire, which heats up and destroys the tissue near the wire tip. And I've tried to illustrate that with these little heat waves here. And this method is really great, because with this technique, scientists can actually vary the intensity and duration of the current in order to control the size of the resulting lesion. However, it destroys everything in that area. And while that's great if you're inserting it into a tumor and want to destroy those tumor cells, It winds up being kind of problematic when it comes to making brain lesions, because it winds up destroying the cell bodies of neurons as well as the axons of the neurons that are just passing through. And so it can be hard to determine whether or not a behavior is stopped because you've killed the cells responsible for it, or if maybe it's controlled by a completely separate brain area, and you just happen to have severed the route by which it carries messages to the body. Neurochemical lesions allow scientists to be much more precise. And there are a number of different ways that neurochemical lesions can be created. One type is referred to as excitotoxic lesions. Excitotoxins are chemicals that bind to glutoamate receptors and cause an influx of calcium into the neuron to such an extent that it kills the neuron. It essentially excites it to death. And one example of an excitotoxin that's usually used in this manner is kainic acid. And this method is really effective, because it destroys the cell bodies of the neurons but it does not influence the neurons whose axons are just passing by. And so you don't need to worry about severing connections in the way that you do with radio frequency lesions, or with simple knife cuts. Another type of neurochemical lesion is created by a chemical called oxidopamine, or 6-hydroxydopamine. And this is a really useful chemical that selectively destroys dopaminergic neurons as well noradrenergic neurons, or neurons that release domamine and norepinephrine or adrenaline. So imagine you have a presynaptic cell, and that cell is releasing dopamine into the synaptic cleft between the cells. But after that dopamine binds with the postsynaptic cell, the body wants to be able to get rid of it or recycle it. And one of the ways it does this is through a process called reuptake. Which is kind of like a little vacuum on the presynaptic cell that sucks all the neurotransmitter back in. Oxidopamine looks a lot like dopamine. In fact, the only difference is the addition of this extra hydroxyl group. And because they're so similar, the presynaptic cell can't really tell them apart. And so oxidopamine is also taken up by the reuptake channels. And then it kills those cells. And this is extremely useful, because it gives us a lot of control. It allows us to be sure not only that we're destroying cell bodies, and not just the axons of cells that are passing by, but it also allows us to kill very specific populations of neurons within specific areas of the brain. So for example, researchers can use this to model Parkinson's disease in lab animals, because it allows them to target and destroy the dopaminergic neurons in the substantia nigra. The same neurons that are affected and destroyed in Parkinson's disease. The last technique I'm gonna talk about is called cortical cooling, or cryogenic blockade. And this involves cooling down neurons until they stop functioning, until they stop firing. And there are a number of different ways that scientists can do this. One way is with the use of a cryoloop, which you can see pictured here. And let me take a minute to write that down. And the idea is that this device, in particular this loop area right here, is surgically implanted between the skull and the brain. And then a chilled liquid is circulated through the loop. But the most important part of this technique is that it is temporary, it is reversible. So while all of the other ablation techniques involve permanently altering brain structures, this one allows us to knock out some nerves, see the effect that it has, and then bring the animal back to normal functioning. Temporary lesions can also be created through neurochemical means. For example, a drug called muscimol temporarily binds with gaba receptors and winds up temporarily inhibiting those neurons, and makes it so those neurons can't fire. And while these aren't all of the methods in which scientists can produce lesions in animals, I think it gives you an idea of how diverse this practice can be. Because while doctors can simply just sever an area with a knife, there are many more methods that are available to them that each have their own pros and cons and can each be used for different situations depending on the effect that the scientist wants to produce.