Iron Engineers in this video today we are going to talk about the basal ganglia we'll go over the basic anatomy basic function and then really dig into some of the pathways direct indirect and then that nigrostriatal pathway and we'll have a little tidbit on the clinical relevance in these basal ganglia lesions. All right, ready? Let's go ahead and get started.
All right, Ningeners, so let's go ahead and start off talking about the basic anatomy of the basal ganglia. So I want to cover two points. One is kind of the orientation of the basal ganglia, and then the components of the basal ganglia, right?
So what we're doing here is we're taking a coronal section. So I'm taking here, I'm slicing the brain here, pulling off the anterior piece, and looking at the posterior piece in this fashion. There's a bunch of different components here, okay?
The first component that I want you to know here that we're going to label one, This is called the caudate nucleus. Okay, the caudate nucleus. Okay, the second part that I want you to know here is this one here in red. This right here is called the putamen.
This is called the putamen. Then the next one is this entire big blue hunk of cheese here. What is this thing called? This is called your globus pallidus.
But there's actually two parts, an internal part and an external part. Okay. So we have the caudate nucleus, putamen, and the globus pallidus internal-external component.
What else is next? The next part is here. These little pink little egg-shaped structures on the sides of the third ventricle.
This blue structure here is the third ventricle. A little fluid-filled space with cerebrospinal fluid. On the sides of it are your thalami. So your thalamus is one of the other components of the basal ganglia.
The next component here. is going to be these green structures here that's kind of a little bit inferior to the thalamus. These are called your subthalamic nuclei. These are called your subthalamic nuclei. And the last component of the basal ganglia is actually in the midbrain, right?
In the midbrain, you have this very special structure here called the substantia nigra. So, we know the basic components of the Basal ganglia and their orientation in a coronal section. Now let's name them and a couple other little specifics.
Alright, beautiful. So we know the components, right? But let's really write out their names. Plus there's a couple other terminology that we have to establish.
So the first component that we mentioned as a part of the basal ganglia is called the caudate nucleus. So this is called the caudate nucleus. Very interesting structure.
The next one we said the second component, this red structure, is called the... Putamen. Now, this is very important. The reason why I want to kind of make some terminology here is that whenever you take the caudate nucleus and the putamen, them together, collectively, they make a structure called the striatum. Okay, so they make a structure called the striatum.
So I want you guys to remember that the putamen And the caudate nucleus combined make up the striatum. Alright, beautiful. The next thing, the third component that we mentioned is the globus pallidus, right? And we said that there was two components. What kind of components?
There was an internal component, so we're going to put globus pallidus internus. And then there was an external component, which is called the globus pallidus externus. So again, this is globus pallidus internus.
Globus pallidus externus. Okay, now there's another term that we have to establish. If you take the putamen and combine it with the globus pallidus, this makes a very special type of name or structure.
And we call this the lentiform nucleus. Okay, so the caudate and the putamen make the striatum and the putamen and the globus pallidus make up the lentiform nucleus. Beautiful. Alright, the next thing that we have to discuss, with my pink marker here, is the fourth component, which is the thalamus. So this is our thalamus, but I actually want to be a little bit specific.
I know you guys remember from the thalamus video, there was two motor nuclei. Dig into your cerebral cortex. What were those thalamic nuclei that we were really actually focusing on here?
Do you remember? It was the ventral anterior nucleus. of the thalamus and the ventral lateral nucleus.
of the thalamus. So when we say that the thalamus is a part of the basal ganglia, if we're really being particular, it's actually the ventral anterior and ventral lateral nucleus of the thalamus. All right, beautiful. The fifth component, the fifth component here of the basal ganglia is called what?
This is called your subthalamic nucleus. Okay, so now We talked about these main ones. Remember, we talked about there was one last component, the sixth component.
What is this? This is very important. What is this final structure here? This final structure here is called the substantia nigra.
So what are these called here? This is called, both of these, is your substantia nigra. Now, the one that we, there's two parts of it we talked about, right?
We're just going to abbreviate them. Zona. Compacta and zona reticularis.
The one that we care about in this pathway is the zona compacta. That's the one that contains all that dopaminergic neurons. Okay, so we've established the components. We've established some specific terminology that I might use throughout the course of this video. The last thing I want us to talk about before we get into the pathways is the basic motor function.
Obviously, I kind of give you the idea what the basal ganglia is involved in. It's motor function. So the motor function... is coordinated by the cerebral cortex, right?
So if you guys remember, we have a couple different regions in the cerebral cortex that are involved in motor movement. Here's your central sulcus, right? This black line here. Behind the central sulcus, you have the postcentral gyrus, which is your primary somatosensory cortex.
And then anterior to this, you have your precentral gyrus, which is where your primary motor cortex is. And then out just kind of anterior to that, you have your premotor cortex, right? Okay, so you have your primary motor, premotor cortex, and your primary somatosensory cortex. These areas kind of combined make up your basically your entire kind of motor cortices. These structures, they decide your voluntary motor movement, right?
What happens is is they send information down from these areas to your muscles via these upper motor neurons down to your lower motor neurons, which go to your skeletal muscles and cause your skeletal muscles to contract, right? So this is called your corticospinal tract. Well, in order for this motor plan to go down to the muscles, you have to kind of have communication with the basal ganglia.
So what I'm going to do here is in the kind of like this green structure here, I'm going to imagine that this is the... Basal ganglia here. Okay, so imagine for a second this is our basal ganglia. These cerebral cortex areas have to communicate their motor plan with the basal ganglia.
The basal ganglia will take that motor plan and modify it in a particular way and send it back to the cerebral cortex to send now the proper motor plan to start movement, stop movement, or modulate movement. What did I just say? What were the three primary functions of the basal ganglia?
To start. Movement, stop movement, and modulate motor movement. So this is all involved with movement.
So it's designed to kind of start or initiate a movement, stop kind of unwanted motor movements, and modulate motor movements. Beautiful. Now let's get into the pathways.
All right. So now what we got to do is, since we've already talked about the basic anatomy, the basic function of the basal ganglia, we really got to kind of expand on that function a little bit more and talk about it. Three particular pathways. The direct pathway, indirect pathway, and the nigrostriatal pathway. The reason why they're important is they basically tell us the three functions.
To start movement, to stop movement, or to modulate movement in some way. So the first pathway that we have to discuss here is called the direct pathway. Now, let's keep it relatively simple here. When we talk about the direct pathway, What I want you to know in the most simplistic way is that this is designed to increase or stimulate motor activity. That is honestly the easiest way.
Or, if you want to expand on that, it's designed to help to initiate motor movements. But I just like to think about it as increasing or stimulating motor activity. How does it do that?
Well, there's a pathway here, right? Let's provide the basic kind of like scaffolding of this pathway. Remember I told you that in order for the cortex, where you have your motor cortex, it's going to send down a motor plan to your skeletal muscles, right? But in order for it to do that, it has to send it to your basal ganglia.
Basal ganglia will then take that information and send it back up to the cortex to completely modify that motor plan. So we have to go from the cortex to the basal ganglia back to the cortex. How does that look?
Well, here you have neurons in your cortex, right? And what they're going to do is they're going to send their axons down. to the striatum.
Do you guys remember what the striatum was? It was made up of the putamen and the caudate nucleus. Then the neurons from the putamen and the caudate nucleus will then move towards the globus pallidus internus.
Then from the globus pallidus internus, these neurons will then go to the thalamus. And you know in the thalamus, you have the particular types of nuclei here called the ventral lateral and ventral anterior nuclei. Their axons will then extend back up to the cerebral cortex.
So this is basically the basic scaffolding of the cerebral cortex involvement with the direct pathway of the basal ganglia. Now, let's dig into this pathway a little bit more. Okay, we got to go over kind of the mechanic, you know, the nitty gritty stuff. From the cortex to the striatum. These types of fibers are called glutaminergic fibers.
What does that mean? That means that the neurotransmitter that these red fibers release onto these blue neurons is actually based on a neurotransmitter called glutamate. We'll go over a little bit more of the detail of this, but for right now, the simplistic way that I want you to remember this is that glutamate is a stimulatory neurotransmitter.
So when it acts on the next neuron, the postsynaptic neuron, it's going to activate it. Okay? So if that's the case then, this neuron is firing lots of action potentials down from the cortex to the striatum, right?
And then what is it going to do? It's going to release glutamate, which is going to stimulate the neurons present within the striatum, right? If that's the case, these neurons are going to be super active, and they're going to send lots of action potentials. down their axons from the striatum to where? So the globus politis internus.
The neurotransmitter that's being released from the striatum to the globus politis internus is actually GABA, gamma amino butyric acid. What I want you to remember, we'll go in more detail later, but simplistically it is an inhibitory neurotransmitter. So when it is released from this Neurons coming from the striatum onto the globus pallidus internus, it's going to inhibit that neuron.
So, if we release a lot of GABA, because this is sending lots of action potentials, it's really going to inhibit this globus pallidus internus. Now, the neurons going from the globus pallidus internus to the thalamus, they're going to have decreased action potentials, right? And...
if there's decreased action potentials, that means that there's less neurotransmitter released from the globus politis internus onto the thalamus. Now, the type of neurotransmitter that's released here between the globus politis internus and the thalamus is again GAVA, which is an inhibitory neurotransmitter. Now, if I'm having less action potentials, I'm releasing GAVA. less GABA onto the thalamic nuclei. GABA is an inhibitory neurotransmitter.
If I have less GABA being released here that means I have less inhibition. So if there's less inhibition this is sometimes referred to as disinhibition or it's released from inhibition and now these neurons in the thalamus are going to be stimulated. And if they are stimulated they're going to send lots of action potentials back up to your motor cortex and the end goal is that now from your motor cortex going down to your skeletal muscles what is it going to do it's going to increase the motor activity of the desired skeletal muscles isn't that cool how the direct pathway does that so that's what I want you to remember for the basics now we talked about glutamate GABA a lot let's go over the basic ways that these are inhibitory and stimulatory neurotransmitters down here in the bottom.
All right, so now let's go over the neurotransmitters a little bit more. Now, remember I said GABA, right? So GABA is an inhibitory neurotransmitter. Let's expand on that a little bit.
GABA has different types of receptors. We're not going to go into the details of it, but there is A, B, and C. But what I want you to know here, the main thing that we're talking about is that GABA binds onto what's called these ligand-gated ion channels. So here's your GABA. It'll bind on to a particular neuron, right?
So here's your postsynaptic neuron in this case. Gabble will then bind on to this receptor. When it binds on to this receptor, what it'll do is, let's say that before there was like a little...
Kind of like thing here, a gate blocking the entry of ions. When GABA binds, what it does is, is it opens up that gate and allows for what? Certain types of ions to move in or out.
Now, if that's the case, then it has to be inhibitory, right? So what happens is very interesting. Positive ions like potassium can leave this neuron or negative ions like chloride can. Enter this neuron. Either way, I'm losing positives or I'm gaining negatives.
What's the overall result inside of the cell? The cell is going to become extra negative. If the cell becomes extra negative, I take the resting membrane potential and drop it below, way below the resting membrane potential. What is that called whenever you drop the voltage below the resting membrane potential? It's called hyperpolarization.
And this type of hyperpolarization is actually called an IPSP, an inhibitory postsynaptic potential. So that is how this does that. And so there's going to be no action potentials carried down this neuron because of how GABA works.
In the same way, we talked about glutamate and how glutamate, we said in the most simplistic sense, is a stimulatory neurotransmitter. The same concept happens here. Glutamate binds onto this ligand-gated ion channel.
Generally, the gate is closed whenever that ligand is not bound. But when glutamate binds, it opens up the gate and then allows for positive ions to flow in. Maybe positive ions like sodium, maybe positive ions like calcium.
And these ions will flow into the cell and cause the cell to become extra positive. As you increase the positive voltage in the cell, what do you do? You take resting membrane potential and move it towards threshold potential. And whenever you hit a particular threshold inside of the cell, that may trigger a action potential. So this is referred to as a EPSP.
So glutamate has a stimulatory effect via this mechanism and GABA has an inhibitory effect via this mechanism. Okay. Now that we've established the basic concepts of that with the direct pathway, we can blast through the indirect pathway.
Alright, so now we talked about the direct pathway designed to stimulate motor movement, start motor movement, initiate motor movement. What's the other function of the basal ganglia? It's designed to inhibit motor activity.
In other words, particularly inhibit unwanted motor movements, undesired motor movements. So the other function of the basal ganglia is carried out via the... via the activity of the indirect pathway of the basal ganglia. And again, the basic function I want you to easily remember this is to decrease motor activity or inhibit motor activity.
But particularly if we're really digging into the detail, it's inhibiting or decreasing unwanted. Let's actually add that in. Decreasing unwanted or undesired motor activity. I really want us to understand that.
Okay, so same concept. We've got to communicate from the cortex to the basal ganglia back to the cortex. But it's just a different route. Let's build our scaffolding for this.
So coming from the cortex, we're going to have neurons going to the striatum. Same thing like we have with the direct pathway. They're going to act on the neurons present within the striatum.
Then from the neurons of the striatum, instead of them glowing to the globus politis internus, they go to the... Globus pallidus externus. Then from the Globus pallidus externus, these neurons will then move downwards to the subthalamus, right?
The subthalamic nuclei, one of the other components of the basal ganglia. Then from the subthalamic nucleus, it will have neurons that will go back up. to the globus pallidus, but to the internal component of the globus pallidus. Then, from the neurons of the globus pallidus internus, which are acted on by the subthalamic nuclei, it will then go to the thalamus.
What type of nuclei of the thalamus are we saying? Particularly the ventral, anterior, and ventral lateral nuclei of the thalamus. And then the fibers from these are sent back up to the cortex.
This is our basic scaffolding. Now let's dig into it. Again, neurons coming from the cortex to the striatum. What type of neurotransmitter are released here? This is glutamate.
Glutamate is what? In a stimulatory neurotransmitter. So what is it going to do? It's going to stimulate these neurons present within the striatum.
What does that mean? If they're stimulated, there's going to be lots of EPSPs and lots of action potentials being traveling. Down these axons. From where?
From the striatum to the globus pallidus externus. Now, these neurons release GABA. GABA is an inhibitory neurotransmitter. If there's lots of action potentials, that means lots of GABA is being released here.
If lots of GABA is being released onto this neuron, this neuron is going to be heavily inhibited. If it's inhibited via the IPSPs and hyperpolarization, then this neuron, when it's inhibited, it's going to send less action potentials from the globus pallidus externus to the subthalamic nuclei, so decreased action potentials. If there's decreased action potentials going from the globus pallidus externus to the subthalamic nucleus, guess what type of neurotransmitter is released here onto the subthalamic nucleus? What type of neurotransmitter is being released here? GABA.
And what do we say GABA is? GABA is an inhibitory neurotransmitter. So what happens here is that means that we're releasing less GABA. Now remember, what do we say? Whenever there is less GABA, that means there is decreased inhibition.
Decreased inhibition is kind of what's called disinhibition, which means that this neuron is released from inhibition and is actually stimulated. Now, Because this neuron, the subthalamic nucleus, a neuron is actually stimulated, what's it going to do? Send lots of action potentials from the subthalamic nucleus to the what? The nucleus or neurons present within the globus pallidus internus. If there's lots of action potentials going from the subthalamic nucleus to the globus pallidus internus, that means lots of neurotransmitters being released here.
What type of neurotransmitter is being released here? Glutamate. Glutamate is a stimulatory neurotransmitter.
That means you're going to have heavy stimulation of these neurons present within the globus pallidus internus. If there's heavy stimulation of the neurons in the globus pallidus internus, that means that you're going to have increased activation and increased action potentials traveling down this neuron. If there's increased action potentials between the neurons from the globus pallidus internus.
To the thalamus, that means lots of neurotransmitters being released here. What type of neurotransmitter is being released here? GABA. GABA is an inhibitory neurotransmitter. So that means lots of GABA is going to be released onto these thalamic nuclei.
If lots of GABA is released, that means strong inhibition of these thalamic nuclei. That means that from the thalamus, if there's decreased stimulation of the thalamus, that means that these thalamic nuclei... are going to send decreased action potentials via their axons to the cortex. And if there's decreased action potentials going to the cortex, guess what? That's going to tell the motor cortex that we want to decrease particular motor activity of a given body part.
Doesn't that make sense? So that's how the indirect pathway is more particularly when we really get down to the nitty gritty is actually working. Now we talked about initiating motor movement, preventing unwanted motor movement, or stimulating decreasing motor activity.
Now we got to talk about how we can modulate the activity of both the direct and indirect pathway. Let's come over to this last part. All right, so the last function of the basal ganglia, remember I told you that it's actually kind of a modulation type of action. The particular name of this pathway that we have to discuss here is called the nigrostriatal interval. pathway.
Alright, so the nigrostriatal pathway is technically really important and it's involved within what? The modulation, okay, of the direct and indirect pathway. So it's going to modulate the activities. Now the best way I like to remember the nigrostriatal pathway is it's trying to amplify the activity of movement.
So how does it actually kind of modulate the direct and indirect pathway? Really the particular way that I want you to remember is that it's designed to kind of amplify motor activity, to really kind of stimulate it. How does it do that?
Well let's first talk about how it influences the direct pathway, and then how it influences the indirect pathway. Okay, so again, have your scaffolding. We can actually kind of blast through this. From the cortex coming down to the striatum, then from the striatum to the globus pallidus internus, from the globus pallidus internus to the thalamus. From the thalamus, we go back to the, we have the two nuclei, back to the cortex, right?
So this is our basic scaffolding. Now, Here's where we add in this extra pathway. Remember we had the substantia nigra, right? Well, what happens is from the, actually the zona compacta, you have neurons that actually ascend upwards and go to the striatum.
I kind of loop this one here. And what they do is they release dopamine onto the actual neurons of the striatum. Now, the type of...
A dopamine receptor is actually what's really specific. What I want you to remember is the dopamine receptor here is actually a D1 receptor. Okay.
And what I want you to remember right now is that this is a stimulatory receptor. We'll talk about a little bit how that actually is happening. But again, it's the same neurotransmitter in both pathways. It's just the receptor that's different in both pathways. So D1 receptor is important for direct pathway and it's stimulatory.
Okay. So what does that mean? Right. Okay. So let's follow this down.
From the cortex coming down to the striatum, what did we say we were releasing? Glutamate. Glutamate is stimulating these neurons, right?
On top of that, you also have this dopamine that's also being released. And what did we say? Dopamine is acting on the D1 receptors on these nuclei and also stimulating them. Now you have an extra kick or stimulus coming from the cortex and from the... substantia nigra.
Now, these neurons, these neurons going from, here it is, these neurons going from the striatum to the globus pallidus internus are going to fire like a mofo. And they're going to send tons and tons and tons of action potentials really, really powerfully to the globus pallidus internus. What does that mean?
The neurotransmitter that's released here, it's actually going to be released in large amounts onto this globus pallidus internus. What's that neurotransmitter? GABA.
If there's lots of GABA, there's lots of inhibition. So that means that this nucleus here, right, this nucleus, this nucleus of the globus politis internus is going to be super, let's make a big negative sign, super inhibited. That means it's going to send very little action potentials, very little action potentials from the globus politis internus to the thalamic nuclei.
If there's very little, here we're going to make like a teensy little arrow, very little GABA, or here we'll do this, lots of down arrows. If there's very little GABA released, there is a significant decrease in inhibition, right? So if there's a significant decrease in inhibition, that's going to result in extra stimulation of the thalamic nuclei. So again, less action potentials, less GABA, less inhibition, more than normal on the thalamic nuclei.
Now those thalamic nuclei are released from inhibition significantly and they're gonna fire like a mofo. And they're gonna send lots and lots and lots of action potentials back up to the cerebral cortex. Telling that cerebral cortex, stimulating it, and then doing what? What was already normal increase in motor activity, it's gonna increase the motor activity even more. So it's gonna want to really help to start motor movements.
Why is this so important? Whenever there's damage of the direct pathway in some way, shape, or form, where you want to increase motor activity, if you damage this pathway, right, particularly damaging the substantia nigra, you know what disease can result from this? Parkinson's disease.
So the clinical relevance here is with respect to a particular disease called Parkinson's disease, right? So Parkinson's disease, what's kind of the characteristic of this? They have difficulty initiating movement, maintaining movement. Right? Why?
Because you've damaged the direct pathway with the nigrostriatal involvement. And now what you're supposed to be doing to increase motor activity, now you can't perform that motor activity very well. And so that's kind of one of the classic things that I want you to remember.
So direct pathway with involvement of the nigrostriatal pathway, damage to that pathway can result in Parkinson's disease. Okay, beautiful. Now let's talk about how the nigrostriatal pathway influences the indirect pathway.
All right, so next one is the involvement of the nigrostriatal pathway with the indirect pathway. Okay, so again, build your scaffolding, right? So from the cerebral cortex to the striatum, right? Then from the striatum.
This is also a good recap, right? Good review. From the striatum to the globus politis externus. From the globus politis externus to the subthalamic nucleus.
From the subthalamic nucleus back up to the globus politis internus. And from the globus politis internus to the thalamic nuclei, particularly ventral anterior and ventral lateral thalamic nuclei. And then from here back up to the cortex.
Good, we've built our scaffolding. Now we have to add in that next extra pathway. What's that next extra pathway that we said is really important here?
That's coming from the substantia nigra, the nigrostriatal pathway. Again, neurons from the zona compacta come here and send axons onto the striatum. So the neurons of the putamen, and we'll kind of loop this around here, and neurons of the caudate nucleus.
Now, the type of receptors... present on the striatum in this indirect pathway, okay, is actually called what? D2 receptors.
D2 receptors, what I want you to remember here is that they are inhibitory, okay? And we'll talk about how they do that. But I just want you to remember where dopamine is released onto these neurons within the indirect pathway, it's going to cause inhibition.
All right, now let's follow this pathway. From the cortex, what do you have? What do we say? You're releasing lots of glutamate onto the striatum, right?
Glutamate has a stimulatory effect onto these neurons. But then you have dopamine that's being released onto the D2 receptors here of the striatum. What's that trying to do? That's trying to inhibit these neurons. So now think about this.
You have normal stimulation, but then coming from the substantia nigra, you have increasing inhibition. What does that mean? Well, normally you'd be sending lots of action potentials from the striatum to the globus pallidus externus.
But because we have some inhibition to these neurons, now there's going to be decreasing action potentials. So now what used to be a lot of action potentials is decreasing action potentials moving from the striatum to the globus pallidus externus. What does that mean? That means less neurotransmitters released here. What kind of neurotransmitters released here?
GABA. GABA is inhibitory. So if there's less action potentials, that means less GABA. Less GABA means less inhibition.
If there's less inhibition of this neuron, it means it's disinhibited and it will be stimulated and fire. So now this neuron is going to fire more and it's going to send increasing action potentials from GABA. the globus pallidus externus to the subthalamic nucleus. If there's increasing action potentials, that means that there's increased neurotransmitter released here. What type of neurotransmitters released here?
GABA. GABA is inhibitory. So if there's lots of GABA released onto the subthalamic nucleus, what does that mean? That means that there is increasing inhibition because GABA is an inhibitory neurotransmitter. If that's the case, then what does that mean?
That means, well, I have two red markers. That means that if there's a lot of inhibition here, there is decreasing action potentials carried from the subthalamic nucleus to the globus pallidus internus. If there's decreasing action potentials, that means less neurotransmitters released. What type of neurotransmitters released here? Glutamate.
If there's less glutamate, what does that mean? That means that there's less stimulation. If there's less stimulation of this neuron, then we can now kind of say that it is actually slightly inhibited. And so that means that there's going to be decreasing action potentials moving from the globus politis internus to the thalamus.
If there's decreasing action potentials going from the globus politis internus to the thalamus, that means less neurotransmitters released here. Less neurotransmitter like which one? GABA. If there's decreasing GABA, that means there's decreasing inhibition. So if there's decreasing inhibition, that's called disinhibition.
So it's released from inhibition, and now it's going to be stimulated. And now the thalamic nuclei are going to do what? They're going to fire like a mofo and send increasing action potentials, now that they're released from inhibition, up to the cerebral cortex. So now the cerebral cortex is going to be stimulated.
And now the motor activity that you were designed to decrease, now you're going to increase the activity, the motor activity. But again, what type? Increase the motor activity of particularly maybe unwanted motor movements. Okay, so you're going to increase the motor activity of the unwanted motor movements.
And in the direct pathway, it also increases the activity of wanted motor movements. All right, so the last thing that I wanted to talk about is remember I said that there was a little discussion here with the D1 receptors and D2 receptors. Again, so we're going to say here we're going to talk about the D1 receptor.
And we said that this is a stimulatory type of receptor. And then over here, we're going to talk about the D2 receptor. And we said how this is an inhibitory receptor.
Let's explain this very basically. Okay, so dopamine, right? It's the same in both of these pathways.
It's the same neurotransmitter that's released. But when it binds onto that D1 receptor, right? The thing is, is it binds onto a G protein couple receptor, particularly a G stimulatory protein. And if you guys remember from the plethora of videos that we've done, G stimulatory leads to an increase eventually in cyclic AMP.
Cyclic AMP will then do what? It'll activate protein kinases. And these protein kinases will do what?
Well, they'll phosphorylate particular channels and allow for positive ions to flow into the cell, leading to stimulation of increasing voltage inside of the cell. So normally you have a resting membrane potential. If you bring in lots of positive ions, that'll bring it to threshold potential. If you bring it to threshold potential, eventually you'll activate voltage-gated channels in the axon and lead to an action potential.
So the D1 receptors, that's how they function is by increasing cyclic AMP. Guess what? The D2 receptors are just the exact opposite. They work via the G-inhibitory protein.
And G-inhibitory protein will actually do what to cyclic AMP? It will decrease the cyclic AMP levels. That means decreased protein kinase levels.
That means decreased phosphorylation of channels. in the membrane and that means what? Less positive ions are moving in here. If less positive ions are moving into the cell that means that you're going to have a difficult time of getting that resting membrane potential to threshold potential, right?
And so because of that this won't be able to reach threshold potential and therefore it will actually lead to decreasing action potentials moving down this neuron, okay? So that's kind of the basic that I want you guys to understand with the dopamine receptors. So I wanted to take a quick little time to just kind of, again, recap, bring a clinical point of the basal ganglia. Why are we learning this, right?
So we talked a little bit about Parkinson's disease. I kind of wanted to expand on that just a little bit more and provide a little bit more clarification. So remember, when we talked about direct pathway, that was designed to increase the motor activity, to start motor activity, to initiate motor activity. Well, what happens if you damage... The direct pathway, which wants to start, initiate, perform motor activity.
Well, now you have difficulty in being able to initiate, start, and maintain motor activity. There is a particular disease process, and this is called Parkinson's disease, right? So we kind of touched on that a little bit, right?
In the same concept, the indirect pathway is designed to decrease motor activity. particularly unwanted motor activity. So now the indirect pathway, right, it's designed to decrease motor activity.
So to prevent unwanted motor movements, right? So if you damage this pathway, you damage the indirect pathway, this can result in unwanted motor movements, right? And these can lead to conditions particularly like Huntington's disease, Huntington's disease, or You know there's another condition where if you have a lot of copper built up in the liver, the liver stops functioning and then it can lead to damage to the actual central nervous system.
It's called Wilson's disease, also known as hepatolenticular degeneration. Or in someone who has rheumatic fever. You know in rheumatic fever we talked about how they can have what's called Syndenham's chorea where the antibodies can attack the actual basal ganglia. The other thing that's actually really interesting is drugs. There's what's called extra pyramidal syndrome.
particularly common in patients who are taking first-generation antipsychotics, right? What happens is that really alters this pathway, particularly the D2 receptors, and can lead to problems like tardive dyskinesia, right? It can lead to akathisia, which is kind of like a restless movement.
It can lead to dystonic reactions, okay? So this is kind of important to provide a clinical correlation of the basal ganglia with particular types of... hypokinetic movement disorders and hyperkinetic movement disorders okay alright so that covers the basal ganglia alright in this video we talk about the basal ganglia the anatomy the function the pathways and a little bit about the clinical relevance I hope you guys like this video hope you guys learned a lot and enjoyed it if you guys did hit that like button comment down in the comment section and please subscribe please subscribe also down in the description box with links to our Facebook Instagram go follow us on there also we have access to our patreon account if you guys were willing to donate money We would truly appreciate it.
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And as always, until next time.