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Course: Health and medicine > Unit 8
Lesson 10: Parkinson's disease- What is Parkinson's disease?
- What is Parkinson's disease?
- Movement signs and symptoms of Parkinson's disease
- Non-movement symptoms of Parkinson's disease
- The basal ganglia - The direct pathway
- The basal ganglia - Concepts of the indirect pathway
- The basal ganglia - Details of the indirect pathway
- Putting it all together - Pathophysiology of Parkinson's disease
- Genetics and Parkinson's disease
- Diagnosing Parkinson's disease
- Managing Parkinson's disease with medications
- Managing Parkinson's disease with surgery
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The basal ganglia - Details of the indirect pathway
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Want to join the conversation?
- 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 at6:30you 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)- 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)
- So if you want to "losen the leash", is the process same as the direct passway?(4 votes)
- direct pathway = initiate & execute voluntary movement = loosen leash
indirect pathway = prevent unwanted muscle contractions = tighten leash
ps. it's "pathway" not "passway"(2 votes)
- 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)
- The substantia nigra degenerates in Parkinson's disease, and the dopaminergic neurons in the basal ganglia break down as well.(2 votes)
- 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)
- So does that mean that the "loosening of the leash" could be a contributing factor to Schizophrenia?(1 vote)
- How are D1 and D2 receptors different?(1 vote)
- Hi, in the video you talked about loosening the leash a little bit and adjusting the leash at5:33, is this also part of the indirect pathway? Or is it basically the same as the Direct pathway? Thanks!(1 vote)
- 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) - 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)
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.