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The basal ganglia - The direct pathway
- [Voiceover] Every day we make hundreds of movements, from reaching for our first cup of coffee in the morning to waving hello or good-bye to someone that we know to using utensils to eat our food. And we actually have this really incredible system in our brains that allows us to make these movements, and it prevents unwanted movements from happening, and it does this in this really smooth, streamlined way that we don't even really notice. So this system is called the basal ganglia, and the basal ganglia is actually a collection of nuclei, and here when we say nuclei what we mean are structures that are just kind of made up of a bunch of neurons. So these little clusters of neurons. So the basal ganglia is made up of a few of these clusters of neurons, these nuclei, and before we actually go through how they together control our movements, let's just first have a look at where these structures are in the brain. So here we have a diagram of the brain, and the way that we're looking at it is as though we sliced it, and we kind of split up the front and the back of the brain, and now we're looking inside one of these sections. And we call this a coronal section. So if we look here, this is the putamen, and over here is the body of the caudate nucleus. And down here we can actually see the tail of the caudate nucleus, and the putamen and the caudate nucleus together actually form what we call the striatum. And if we look back over here, we can see what we call the globus pallidus, and this is the external part, the external globus pallidus, and this is the internal part. And if we look down here at this black structure that we have on our diagram, this is the substantia nigra, and we call it this, we call it the substantia nigra, which means black substance, because the neurons here they have this pigment in them, this coloring, that makes them actually look black in the brain. And we can actually see this darkness of the substantia nigra quite nicely if we look at an MRI. So in this MRI of the brain, you can see these little black areas here on both sides of the brain, and this is the substantia nigra. And if we head back over to our diagram of the brain, we have over here the subthalamic nucleus, and we call it this because it actually sits below, sub meaning below, the thalamus. So except for the thalamus, these are the components of the basal ganglia that we need to know about to talk about movement. So all of these structures, including the thalamus, they work together to control our movements, and the way that they do that, the way that they communicate with each other, is through these pathways. And we're going to talk about these pathways, but this communication in these pathways is controlled by neurons, neurons talking to each other. So before we dive into these details of these pathways, I'm going to throw some terminology at you, just so that things make a little bit more sense as we're going along. So when a neuron goes from one part of the brain to another, it actually communicates with another neuron at its destination, and it does this at what we call a synapse. And it's here that the first neuron, which we call the presynaptic neuron, that came from the first location, and the postsynaptic neuron, which is in the arriving destination, this is where they talk, and they talk by sending chemicals that we call neurotransmitters. So the presynaptic neuron sends a bunch of chemicals to the postsynaptic neuron, and depending on what kind of chemicals they send, the postsynaptic neuron may have different things happen to it. So one important neurotransmitter that the presynaptic neuron can send is GABA, and GABA we call our main inhibitory neurotransmitter, and we call it this, this inhibitory neurotransmitter, because it has this inhibitory effect on the postsynaptic neuron. So it kind of turns it off. It turns its activity off. It inhibits it. So another neurotransmitter that the presynaptic neuron could send is one that excites the second neuron, excites the postsynaptic neuron and turns its activity up. And the main excitatory neurotransmitter is called glutamate, and this increases activity in the postsynaptic neuron when we excite it. So all of this will become important as we go through these pathways. So there are two big things that we need help with, when it comes to movements. The first is that we actually need help making a movement. So we need help getting from saying to our bodies, hey, I want to move my arm, I want to grab that cup of coffee, to the point where we actually are moving our arm. So everything in between we need help with. And the second thing we need help with is not moving, making sure our muscles are not moving when we're at rest or when we just don't want them to. So the pathway that takes care of this first one here, we call the direct pathway, and the pathway that takes care of the second one here, we call the indirect pathway, and both of these pathways, we call these the pathways of the basal ganglia. So they're involving those structures that we looked at before when we were looking at the brain. And we're going to go through the direct pathway. So these are the components of our pathway, and before we begin, it's important that we recognize that the thalamus here, the thalamus, it's normally under what we call inhibition. So this means that unless things change, the thalamus is, its activity is being suppressed. It's not allowed to be as active as it wants to be. So the aim of the direct pathway is to take away its inhibition, to allow the thalamus to be more active, and that's because the thalamus is what talks to the motor cortex, which then talks to our muscles, telling them to move. So if we want to get movement going, if we want to move our arm, we need the thalamus to be able to be active. So that's the aim of the direct pathway. So the first thing that happens is up here, in the motor cortex, and that's when we say, hey, I want to move. So when we say that, an excitatory neuron from the motor cortex goes to the striatum. So this is something that's already there, but the motor cortex sends an excitatory message to the striatum, and this excitatory neuron here, it actually synapsis with an inhibitory neuron in the striatum that's heading to the globus pallidus internal. So when this exitatory message comes down this excitatory neuron and synapsis on this inhibitory neuron in the striatum, heading for the globus pallidus internal, what this does is it excites the striatum, and these inhibitory neurons in the striatum, they become more active, because the striatum is excited. So these inhibitory neurons, they're more active, and so they actually inhibit the globus pallidus internal more than it would have been before we sent this excitatory message from the motor cortex. So this excitation that's happening here is happening because of glutamate being released, and this inhibition on the globus pallidus internal is happening over here because of GABA being released. So the globus pallidus internal normally is what's actually holding the thalamus down, keeping its activity down. So when its inhibited by these striatal neurons, its activity is turned down. So when the activity of the globus pallidus internal is turned down, it can't inhibit the thalamus as much as it normally would. So the thalamus is now no longer as inhibited as it was, so it's able to get a bit more excited, a bit more active, and it's able to send excitatory messages to the motor cortex, because it has these excitatory neurons that go there. So it sends more and more messages to the motor cortex, and the motor cortex gets more active, and it then sends excitatory messages to the muscles that we want to move. So that's how we make those movements that we want to make. So while all of this is going on, the substantia nigra and the subthalamic nucleus, they're actually kind of working in the background to fine tune things. So the substantia nigra has these neurons that are dopamine neurons, and they actually go from the substantia nigra to the striatum, where they synapse with inhibitory neurons in the striatum that are going to the globus pallidus internal. So kind of those ones that we talked about before. So when the substantia nigra is more active, it sends more and more dopamine to these inhibitory neurons in the striatum that are heading for the globus pallidus internal. And these inhibitory neurons in the striatum, they have these dopamine receptors that we call D1 receptors. And when dopamine from the substantia nigra binds to these D1 receptors on these inhibitory neurons in the striatum, they get excited. And so, the dopamine coming from the substantia nigra further excites these inhibitory neurons heading for the globus pallidus internal, and this results in even more reduction in activity, even more inhibition of the globus pallidus internal, and this allows the thalamus to be even more active, because we've further blocked that signal. And back over here, the subthalamic nucleus is actually what's exciting the substantia nigra. So it sends excitatory messages through excitatory neurons from the subthalamic nucleus to the substantia nigra, and this is what excites the substantia nigra and allows it to send more dopamine to the striatum. And the substantia nigra can actually talk back to the subthalamic nucleus, and it does this through inhibitory neurons, and this allows it to say, hey, stop exciting me, I've had enough excitement. So it actually inhibits the subthalamic nucleus, which then stops the subthalamic nucleus from being able to excite the substantia nigra. So when this happens, when the substantia nigra isn't being as excited by the subthalamic nucleus, then it's not adding to that extra activity in the thalamus. It's not allowing the striatum to further inhibit the globus pallidus internal. And so, we don't get as much movement from muscles as we would if the substantia nigra was excited. So together these structures in the direct pathway, they work together to ultimately increase excitation of the motor cortex, so to make it more active and allow us to make more muscle movements.