Hello everyone! Welcome to advanced neurobiology! Neuroscience is a wonderful branch of science on how our brain perceives the external world, how our brain thinks, how our brain responds to the outside of the world, and how during disease or aging the neuronal connections deteriorate. We’re trying to understand the molecular, cellular nature and the circuitry arrangement of how nervous system works. Through this course, you'll have a comprehensive understanding of basic neuroanatomy, electral signal transduction, movement and several diseases in the nervous system. This advanced neurobiology course is composed of 2 parts (Advanced neurobiology I and Advanced neurobiology Il). They are related to each other on the content but not on scoring or certification, so you can choose either or both. It’s recommended that you take them sequentially and it’s great if you’ve already acquired a basic understanding of biology. Thank you for joining us!
6.2 Basal ganglia and its two pathways
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從本節課中
Movement and movement disorders II
教學方
Chenjian Li
Professor
Donggen Luo
Research Fellow
Yan Zhang
Professor
When we understand the structure-function relationship between the two.
So let's look at the basal ganglia components.
There are several nuclei in the basal ganglia.
It consists of corpus striatum, which includes striatum,
which includes caudate and putamen.
It has pallidum, then it is divided into external and internal globus pallidum.
It has a subthalamic nucleus and a substantia nigra.
Substantia nigra, in Chinese, we call it [FOREIGN] because the color is black.
That is further divided into two parts.
One is substantia nigra pars reticulata and that is projection.
The cell body is in substantia nigra pars compacta.
That's where the neural cell body is.
Okay, let's match these guys to the real thing.
Now this is a view that is a cross section of the brain.
So you are cutting the brain this way, and you're looking at it this way, okay.
When we look at these maps, the very first thing,
the easiest thing is to find the landmarks, right?
If you come to Peking University, you have several landmarks.
One is [FOREIGN] which sticks out and then there's the lake, so everything is
on the east side of the lake, or on the north side of something-something.
So what are the big landmarks you can find here?
Ventricles.
Those two big holes right in the middle, one left one right.
Exactly.
So if you look at that and, above the ventricle,
what is that white thing that connects left and right?
>> Corpus callosum.
>> Corpus callosum.
Very good, very good.
Are you heading to a medical school?
>> No.
>> Too bad.
If you want, I can write a good letter.
So if you look at the two big holes, that's the ventricle, [FOREIGN].
That's why we call our part that we're going to study today,
basal ganglia because they are at the base of the ventricle.
Okay.
Now, let's look at those things.
Here is putamen, that's the area that's caudate nucleus.
That's the one immediately next to the ventricle.
Here's thalamus.
Here's globus pallidus.
Oops, sorry.
So these are the structures that are important and
they make, Make basal ganglia.
If you look at the brain from another angle, this cut,
as your are cutting the brain this way and you look from bottom to top.
Similarly, you can recognize the ventricle right away,
and you can see that there are caudate nucleus, there's a putamen,
there's globus pallidus and so forth.
So overall, those structures, they are somehow beneath the two ventricles,
that's why they're called basal ganglia.
That's the anatomic discussion, and
remember that we're going to come back to that when we look at diseased brains.
Now these structures, when they are there, they have the cell body and
they have the projection.
And the projection relates to the next order of neurons and
the next order of neurons.
So we are talking about an information flow and
this information flow depends on the neural connection, right?
So let's look at the functional connection of these guys in this context.
In the basal ganglia, there are two pathways that information can flow.
One is through the direct pathway, and the other one is through the indirect pathway.
The beginning part and the end part is the same.
The beginning part goes from cortex, for
example, the information feeds into striatum.
Striatum, then it splits, either it decides to go through the direct pathway
that goes from the bottom arrow all the way to SNR or,
it goes through the globus pallidus as an intermediate station and
then jumps to the final destination.
By adding that middle part, interestingly,
it completely changed the net result
of activation on both the direct and indirect pathway.
Now how does that work?
By adding one thing, how does it change?
That is years of years of research, and so far, we have been able to
sort of see the outline of that projection.
I have made another figure for you.
And if you follow me step by step, I guarantee,
it will be complicated and complex, but
it is beautiful and you will understand it, and you will be able to memorize that.
Okay, so they way I draw this diagram is as follows.
There is a dotted line, a square in the middle.
Do you see that?
Okay, anything inside of that dotted line, is the basal ganglia.
Everything inside of that, that's basal ganglia.
Then from outside, you have the input
to the basal ganglia from cerebral cortex and frontal lobes, so on and so forth.
Feed in.
The net output of basal ganglia is on
the right hand side, the thalamus, okay.
Of course, thalamus is looping back to work on the frontal lobes and cortex.
However, think about the basal ganglia as one unit.
It has an input, it has an output overall.
Everybody follows me so far?
Okay, good.
Well, if you have input, you've gotta have a place that receives the input, right?
So that's why I draw a unit, a nucleus,
a group of neurons and it's called input neurons.
They receive input.
If you want to output something, sending out messages,
you've gotta have something that does the job of output.
Okay, so input-output, easy.
Now after those two, you can design some modulatory units, right?
Now there are three, what I labelled intrinsic nuclei.
Those are the guys, they don't directly receive information from outside.
They don't send information directly outside.
What they do is that they modulate either the input place or the output place.
Easy to understand?
Okay, now if you think life is that easy, ha ha.
Give you one layer and two layers of complexity.
Let's take a look at what are t, and
what are the neurotransmitter system they are using?
Is it excitatory or is it inhibitory?
Now does everybody understand by now, for example,
glutamate is an excitatory neurotransmitter,
whereas GABA Is an inhibitory neurotransmitter.
Everybody understand?
Good.
From cerebral cortex right here, frontal robes,
when they get their information through into
basal ganglia, they are arrive at striata.
In Chinese, striatum is translated as [FOREIGN]
Okay, now their input,
the neurotransmitter that they use is basically glutamate.
It's the major excitatory neurotransmitter.
And this striatum, substantial negra right here,
that's where the dopaminergic cells are and they send their axons to striata.
So that's one layer of modulation.
Striata can go directly to GPI and
SNR through the direct pathway,
because there's nothing in between, they just go straight from A to B.
That projection is using GABA as a neural transmitter.
Therefore, this innovation is an inhibitory one, right?
From GPI to get outside of basal ganglia, that is thalamus.
That projection is again, GABAergic.
If you go through the indirect pathway however, you actually add something here.
So the story goes, striatum goes to GPE and that projection is GABAergic.
From GPE to STN, that is GABAergic.
However, STN, when it goes to GPI, it changed.
It's actually a glutamatergic innovation, which means it's excitatory.
Now how does this simple adding
of one component in the middle, how does it change the whole output?
So let's go through that one time.
All right, so follow me.
From the cerebral cortex, an information comes in that's excitatory.
So that information flow in excites striatum cells.
When these cells are excited, if they go this way,
they will inhibit GPI neurons.
When you inhibit GPI neurons, but remember GPI neurons,
they themselves are inhibitor neurons.
So the inhibition of inhibitory neurons will eventually excite the whole output.
Therefore, if you go through that straight line from left to right,
the direct pathway,
the net result will be the signal is going to excite
thalamus, which is going to in turn, loop back
to activate all the components that we need to initiate and maintain movements.
So the direct pathway,
the net result is to get people moving, maintain the movement.
Easy.
The beauty of that is, our brain has always been
intrinsically designed to strike a balance.
So we have the indirect pathway.
The first two steps are very similar.
So information comes in and you excite the striatal neuron,
these are GABAergic neurons, they come down to GPE that,
itself is a GABAergic neuron.
When that one gets excited, it goes to here.
That means its minus-minus, its going to excite this guy right?
The excitatory like this one, that will input into GPI.
However, you are activating
