The basal ganglia - Details of the indirect pathway

- [Voiceover] So in this video we're gonna take a look at the indirect pathway. That circuit between some of the nuclei, of the basal ganglia, that helps to make sure that we don't make any unwanted muscle movements. So maybe an unwanted movement would be throwing a hot cup of coffee at your crush on your first date. That would definitely be an unwanted movement. But before we get into all the, all the details of this pathway and see how we can avoid this unwanted muscle movement that would definitely ruin our first date, let's just take a look at this special structure here, the thalamus. Now, the thalamus, it really really likes chatting with the motor cortex. And this is the motor cortex here. This structure that chats with our muscles, and helps to control them. Now if the thalamus could have its way, it would just send tons and tons of excitatory messages to the motor cortex, and just turn its activity up, turn the activity up in the motor cortex. And when the activity in the motor cortex is turned up, the motor cortex chats more with our muscles. And this turns their activity up, and this makes us move more. So when I think of all of this, I like to picture the thalamus as a puppy. A really excited puppy that just cannot be trusted. And it needs to be kept on a leash, because that's what you do with puppies that can't be trusted, right? And we keep it on a leash to control how much it can run around and cause trouble. And in this case, the trouble is the thalamus overexciting the motor cortex, making it too active. Because that makes our muscles too active, and that makes us move too much. So we actually have this leash in the brain. We have a leash for the thalamus, and it's the globus pallidus internal, one of these nuclei of the basal ganglia. So this is the globus pallidus internal here, and it controls the thalamus, it keeps it on a leash by sending it these inhibitory messages, and this keeps the activity in the thalamus down. So this is what the globus pallidus internal does in the brain. It keeps the thalamus on a leash. And when the basal ganglia work together to keep us from making an unwanted movement, what they do is they tighten the leash on the thalamus. They make it even less active, right? Because you pull that leash in, and it can't run around as much. So to do this, all they do is they, they chat with each other, and ultimately they send a message to the globus pallidus internal, and they tell it to tighten that leash; to send more inhibitory messages to the thalamus. And this turns the activity in the thalamus down. So it can't chat with the motor cortex as much. So that's the aim of the indirect pathway: to tighten the leash on the thalamus by chatting with the globus pallidus internal. So let's go through this pathway and have a look at how it all happens. So the first thing that happens is the motor cortex, it chats with the striatum, and it turns up activity in the striatum. So to do that, it sends this excitatory message along this excitatory neuron here that heads over to the striatum. And so the striatum gets really excited, right? It gets excited, and its activity, it turns up. And so, the striatum has these neurons here, these red neurons, let's draw these in red, that are inhibitory neurons that head over to the globus pallidus external, that other part of the globus pallidus. So when the striatum gets excited, these red inhibitory neurons get excited, and they turn down activity in the globus pallidus external. So we have these neurons that go from the globus pallidus external to the subthalanic nucleus. So, when the globus pallidus external's activity is turned down, it can't chat with the subthalanic nucleus as much as it used to. And what it usually does, is it normally kinda holds down the activity in the subthalanic nucleus. So, when it's not so active, it can't do that. So the subthalanic nucleus, it gets more excited, right? And this is the really important part. So this is the part that matters, is, the subthalanic nucleus, it gets excited, and it's what sends excitatory messages to the globus pallidus internal, our leash on the thalamus. So what happens if we excite our leash? Well, that's gonna tighten our leash, right? Because we have our leash, our inhibitory neurons, that go from the globus pallidus internal to the thalamus, and so if we excite those neurons, we're gonna, we're gonna tighten our leash. Because those neurons are inhibiting the thalamus. So all that kind of, all that you need to kind of get from this is that, when we don't want to move our muscles, the motor cortex sends this little signal, it goes through this little pathway here, and the end result is that we excite the globus pallidus internal, and that tightens our leash on the thalamus. And so you know from before that, if we tighten that leash, if we inhibit the activity of the thalamus even more, we're gonna have less chatting between the thalamus and the motor cortex, and less chatting with our muscles, between the motor cortex and our muscles, right? Now, there's a little bit more to the pathway. Remember what we said before, about how we want to be able to adjust our leash? Well, we have something kind of in the background that does just that. It adjusts our leash based on what we need to do. So if we head back over here to the subthalanic nucleus, it actually chats with the substantia nigra. And, the substantia nigra, what it does in this pathway is it, it kind of does the opposite of what we just did. It is our adjustment of our leash, it lets our leash out a little bit to allow our muscles to move a bit more. So, we'll just go over how that happens, but that's, that's the important part. That's the goal of the substantia nigra in the indirect pathway. So the subthalanic nucleus, it turns up activity in the substantia nigra. So it does that by these excitatory neurons, by sending these little excitatory messages. And the substantia nigra, it has these other types of neurons, these dopamine neurons. And these dopamine neurons head over to the striatum. And, they chat with these excitatory neurons, these neurons that turn up activity, and these inhibitory neurons here, that go to the globus pallidus external. So when the substantia nigra gets excited, when it's deciding that it needs to allow the thalamus to be out a little bit more on its leash, to allow it to have a bit more, a bit more freedom, and allow it to play a bit more, it sends dopamine to the striatum. And, the dopamine binds to these little receptors here on these excitatory neurons, and these receptors are called D2 receptors, and when dopamine binds to these, it turns down activity in the neurons, in these excitatory neurons. And so they can't, they can't chat with these inhibitory neurons as much and turn their activity up. So what happens is these inhibitory neurons that would be inhibiting the globus pallidus external, they're not able to do their job as much as they were before, when we were turning their activity up. So they can't inhibit the globus pallidus external as much as before. So that's kinda the opposite of what we had before, right? So before, we were inhibiting the globus pallidus external, and now the substantia nigra is kind of taking away some of that, it's allowing the globus pallidus external to be a little bit more active. So that means that the globus pallidus internal is gonna be a little less active. And so if the globus pallidus internal, our leash, our leash on our thallamus, is less active, then that means that it can't hold the leash so tight. It's gonna have to let it go a little bit. And the thalamus is gonna be allowed to play a bit more, it's gonna be allowed to be more active. So it's gonna talk to the motor cortex more, and the motor cortex is gonna talk to our muscles more. And we're gonna have more muscle movement. And the substantia nigra is smart, right? It knows that our dog cannot be trusted, so, we need to control how much we're letting it out. We can't just let everything go. So the subtantia nigra knows when enough is enough, and it sends messages back to the subthalanic nuceus telling the subthalanic nucleus to stop telling it to be more active. And the substantia nigra stops allowing this little pathway to let our leash out, right? So that, that is the indirect pathway. That's how these structures talk to each other, to adjust the leash on the thallamus. And that's how they adjust how much movement we make.