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The basal ganglia - Details of the indirect pathway

Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT related content. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video. Created by Emma Giles.

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  • spunky sam blue style avatar for user Chirrup
    I have a question about the different dopamine receptors. In the Direct Pathway video (https://www.khanacademy.org/science/health-and-medicine/nervous-system-diseases/parkinsons-disease/v/the-basal-ganglia-the-direct-pathway) you mention that the Dopamine binds to the D1 receptors whereas here at you say that the dopamine binds to D2 receptors. Is that how the substantia nigra 'differentiates' between the direct and indirect pathways? Are there different regions in the Striatum which contain D1/D2 receptors?
    Many thanks :)
    (11 votes)
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    • aqualine ultimate style avatar for user Crystal Teh
      Dopamine is an immediate metabolic precursor of norepinephrine and can be binded at both D1 and D2 receptors. D1 subtype is the most abundant dopamine receptor in the CNS.
      D1 stimulation mainly causes the dilation of the renal arteries
      D2 stimulation inhibits production of cAMP in the nerve endings
      Though both receptors plays a role in motor actions and also working memory.
      As far as I know, these receptors are widely distributed in the brain; different areas have different densities of D1 and D2 receptors.
      (8 votes)
  • duskpin sapling style avatar for user Grace
    So if you want to "losen the leash", is the process same as the direct passway?
    (4 votes)
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  • blobby green style avatar for user u1073063
    Is it the destruction of the substanitia nigra OR the destruction of the dopaminergic neurons (or BOTH) in PD. The substantia nigra is a structure that houses the DA neurons - is this correct? Does the Subst. Nigra still house the DA neurons which have been rendered inactive by a-synuclein + other proteins (LEWY) or does the Subst-nigra degenerate and breakdown?
    (2 votes)
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  • spunky sam blue style avatar for user devin.reid357
    In the direct pathway, the substantia nigra releases dopamine to further excites the inhibitory neuron from the Striatum (via D1 receptors) going to the Globus Pallidus Internal. This means that the Globus Pallidus Internal's inhibitory function on the Thalamus is turned off. Allowing movement. How then does the dopamine in the indirect pathway, which is binding to D2 receptors, not also bind to the D1 receptors? What prevents these pathways from operating at the same time?
    (1 vote)
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  • hopper cool style avatar for user Wei Wei
    So does that mean that the "loosening of the leash" could be a contributing factor to Schizophrenia?
    (1 vote)
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  • duskpin sapling style avatar for user Grace
    How are D1 and D2 receptors different?
    (1 vote)
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  • duskpin seedling style avatar for user Claudia  Chan
    Hi, in the video you talked about loosening the leash a little bit and adjusting the leash at , is this also part of the indirect pathway? Or is it basically the same as the Direct pathway? Thanks!
    (1 vote)
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  • duskpin ultimate style avatar for user Kevin Chang
    So the subthalamic nucleus and substantia nigra can create both more and less movement?If so, is there a specific part of each that is responsible solely for each type of function?

    Correct me if I'm wrong, the subthalamic nucleus has 3 possible functions:
    1. incites globus pallidus internal
    (less movement)
    2. incites substantia nigral function that inhibites d2 recepters which = more globus pallidus external activity=less of itself (?)
    (less or more movement?)
    3. incites substantia nigral function that means more binding to d1 recepters, which = less active globus pallidus internal
    (more movement)
    (1 vote)
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  • blobby green style avatar for user margobutton26
    Can you please provide the name of the cell type for the "excitatory" neurons in the striatum than receive dopaminergic input from the Substantia Nigra?
    (1 vote)
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Video transcript

- [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.