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PROFESSOR: The talk today at 4 o'clock is on somatosentry
cortex, which is, of course, relevant to this class as are
a lot of the talks in the department.
But this should be particularly interesting if
you're interested in how neocortex works.
Somatosentry systems has been a major part of that work.
All right, we were in the middle of talking about the
corpus triad.
And then I talked about some of these pathologies that more
people showed these peculiar increases in movement,
abnormal movements, or disturbed movements, in
various ways And I pointed out that some of that's due to the
fact that many of the striatal connections are inhibitory.
They use GABA as a transmitter.
And we'll see a little more of that today in the anatomy.
I was showing you some of the textbook pictures that always
emphasize the dorsal striatum.
And they omit entirely from their pictures the ventral
striatum that are more closely associated
with the limbic system.
And in fact, in the book chapters you've been reading,
I've put the ventral striatum first in the limbic system
chapter, in the limbic system unit.
But it comes up again in [UNINTELLIGIBLE] striatum.
It has to to get a more complete view of the striatum.
So why is that that so much emphasis is placed on the
dorsal striatum?
Why would they forget about a whole region of the brain?
It doesn't make any sense, does it?
Well, they didn't know how to classify it.
Remember the anatomy of these structures wasn't all that
well known.
And when veteran anatomical techniques started to be
developed with [UNINTELLIGIBLE]
work on silver stains and the later development of methods
for tracing connections based on injection of various
compounds like horseradish
peroxidase fluorescent molecules.
It takes a lot of time to study.
And every time new methods were developed, they sort of
restudied major connections in the brain.
But they didn't get around to every little detail.
And the limbic system is a diverse collection of
structures.
So only when knowledge began to accumulate on limbic system
connections they begin to make some more sense out of the
order and realize that there was a whole group of
structures that could be put together in a so-called
ventral striatum.
And that was first done here at MIT by Lennart Heimer and
his student, which I mentioned earlier.
So we can talk about a ventral striatum
and a ventral pallidum.
And I really can't ask students to
memorize all these things.
The dorsal part is clear.
I'll try to make the major outlines clear here.
Part of the ventral striatum, equivalent to the dorsal
striatum but located ventrally and really it's more ventral.
And it's just below the dorsal striatum, below the putamen.
And below the caudate and putamen it's called the
nucleus accumbens.
It's a particularly large part of that region.
It's right next to the bed nucleus of the stria
terminalis.
And it gets its input from these limbic system areas
we've been talking about, the amygdala, the hippocampal
formation, major inputs from those structures.
And it also gets, just like the dorsal striatum, gets
dopamine axons.
But the dopamine axons are not coming from the major part of
the substantia nigra, which go to the dorsal striatum.
They go for the most medial part of the nigra and from the
ventral tegmental area, which is sort of like a medial
extension of the nigra and was probably the
earlier system to evolve.
All right, well none of that--
I'm not sure how much I explained
all that in the book.
Here's this medial view of the rodent hemisphere, the
embryonic human hemisphere.
And I've marked what's often called the allocortex.
That is the cortex that's not neocortex.
So it's simpler cortex, not six layers like a neocortex,
but thinner cortex, some of it only one cell layer, like the
hippocampus, the most medial edge here.
But then as you go out towards the neocortex,
you get more layers.
And I would include all the cingulate cortex in that,
which is usually four-layered cortex.
But it's never as complex as the neoortex.
It's more similar to the dorsal cortex of non-mammals.
And I've included here the olfactory bulbs,
which are our cortex.
Many anatomists wouldn't do that.
But because of its close relationship with the limbic
system structures that encompass most of these other
structures, I think we can include the olfactory bulb.
OK, so then that's all this cortex at the medial fringe of
the hemisphere.
Or you could, if you're approaching it from the
lateral side, it's at the lateral fringe.
But it's coming around and then underneath.
But this is the striatal structures, the ventral
striatum, ventral pallidum.
And I've extended it in this picture all the way up to
include the septal region there.
And here's the amygdala.
And here's the structures we've lumped together in the
basal forebrain, the nucleus accumbens is right in there.
This is a quick summary of the kinds of connections.
We go from neocortex, the major input, to the dorsal
striatum is from the neocortex.
And the dorsal striatum projects out, mostly through
the globus pallidus.
Now there are other longer connections of the dorsal
striatum as well.
That's the [UNINTELLIGIBLE], for example, that goes
directly to the substantia nigras.
So I could've added substantia nigra to this.
Well similarly, the allocortex, these limbic
system structures, project to the ventral striatum and major
inputs to the ventral striatum.
It's from the allocortex, the inputs from above anyway.
And most of the outputs of the ventral striatum, just as in
the case of the dorsal striatum, go through
structures we can call the ventral pallidum.
And again, like the dorsal striatum, it has some longer
connections, too.
There's some connections that go directly to the midbrain,
for example.
The limbic area is the midbrain.
Now I'm putting this in for reference because I don't
require people to memorize this.
But this is in the Swanson book.
And it's a very interesting way he's divided up the
striatal and pallidal structures.
He starts out with what is best known, the dorsal
striatum and pallidum.
And here's the two components.
The striatal components are caudate and putamen.
The pallidal components are the two parts of the globus
pallidus, GP.
And I just pointed out here that in small rodents and in
some other animals the GPI isn't like in humans.
They're just cells embedded in the peduncle.
But they're equivalent cells.
There on the output side of the striatum.
They receive input from the caudate and putamen.
And now we come to the ventral striatum.
What he does is he says, well, part of this we'll call
ventral striatum and pallidum.
And we'll call the ventral striatum the accumbens, the
olfactory tubercle, and the deepest part of the striatum,
that they sometimes call the fundus of the striatum, the
fundus striati.
And the pallidal components get the major outputs of these
structures.
And he likes to name two here that--
You can see why I don't want you to memorize it.
It's easy for me because I know all these structures.
But when you've not encountered them before--
But these are all structures in those pictures of the basal
forebrain, except I'm not sure I was naming the magnocellular
preoptic nucleus because it's really part of the
hypothalamus, the very anterior end of the
hypothalamus.
But remember hypothalamus and basal forebrain are really a
continuum there and that the anterior end of the
hypothalamus, sort of the caudal part of the basal
forebrain is this large cell preoptic nucleus.
And the substantia nominatis sort of sits in between the
amygdala and the hypothalamus.
So it's similar to the magnocellular preoptic
nucleus, just a more laterally located.
Well then he says, but there's more.
There's a medial part of the ventral striatum.
He calls it the medial striatum.
And then it has a pallidal component, too.
And they're simply the two parts of the septal area.
The medial part is the larger cells.
And he lumps that together with these large cells that
extend further down on the band of large cells going down
to the base, the nucleus, the diagonal band.
And then this striatal part is the lateral septal complex.
Well, that doesn't mean the connection are all
exactly like this.
For example, the medial septum provides major input to the
hippocampal formation.
And that's very different from anything we see up here in the
dorsal striatum.
And then the most awkward part, the caudal rostral, I
think it's a horrible name.
But the reason he's calling it that is part of it's very far
caudal, namely the amygdala, parts of the amygdala.
So he's naming those parts the amygdala here.
And the pallidal component corresponding to that part of
his limbic striatum is the bed nucleus of the stria
terminalis so the [UNINTELLIGIBLE] output side.
If you just take all of this, it's what I'm
calling ventral striatum.
I'm using ventral striatum in a broader way to include the
limbic components of the striatum.
So it's all these structures in this area here.
OK, now a little bit about topography.
Of this please know at least what's up here and then know
that there are parallels in the ventral
in the limbic part.
Now there's a typography.
And this is very important to understand something about
function and the effects of brain damage.
The entire, or just about the entire, neocortical mantle
projects to the caudate and putamen, projects to the
striatum, neocortex.
And then the limbic cortex, just about all of that
projects to the ventral striatum.
And these have some kind of topographic organization.
The major topography is the one that [? Burdall ?]
put in this figure.
The central cortex, here's this the central fissure.
What's just behind the central fissure, this cortex?
It's the matosensory cortex, the one the talk's going to be
about today.
That's getting input from the ventral thalamus, getting
input from our hands, our feet, our lips, all the parts
of the body, the body surface, and also from the joints and
muscles, proprioceptive input because it's given feedback
about movement.
And in front of the central fissure is what we call the
motor cortex, primary motor cortex, where if you stimulate
you get tiny little movements.
It's where we get fine muscle control.
And then right in front of that what we call premotor
cortex where you get somewhat more
organized patterns of movement.
That is all central cortex, supplementary motor area,
motor cortex, and somatosentry cortex.
And that cortex projects to the part of the dorsal
striatum that's lateral to the internal capsule.
So a little bit odd the way he's done the picture here but
that's putamen there.
The caudate gets the inputs from the rest, from the cortex
anterior to the premotor cortex, this
vast area in human.
It's not so vast in other mammals, only in the most
advanced mammals, especially human, the prefrontal areas,
includes areas controlling eye movements here.
Every time we make a voluntary eye movement or someone says
move your eyes to the right and you follow the
instructions, you're using cortex in here that's getting
input by way of association areas,
including the speech areas.
But there's many other areas in prefrontal cortex, some of
which we really don't know much about.
That's projecting mostly to the head
of the caudate nucleus.
And then this vast area of cortex behind somatosensory,
including all of this cortex we call parietal cortex,
occipital cortex, and temporal cortex, the temporal or
neocortex, projects partly to the head of the caudate but
also to this whole tail of the caudate.
So I want you to think about what that tail is.
It's just part of the striatum that's separated by the
internal capsule from the rest of it.
Remember when we saw those pictures of caudate before in
human [UNINTELLIGIBLE], and we'll see more pictures here
in a minute, you always see the caudate located medial to
the internal capsule fibers in animals where the internal
capsule fibers are bunched together.
So medial to it is the caudate.
Lateral to it is the putamen.
Well, when you get in front of the internal capsule, it's a
little bit arbitrary where we won't call
it caudate or putamen.
We call most of that caudate up in front here.
But as you go back that part of the caudate, as the
temporal lobe forms, gets pulled around.
And I will show you that here in a minute.
But because of this topography now, different parts of the
striatum have different functions just like different
parts of the cortex of different functions.
So if there's damage in the putamen, to the part that's
getting somatosenory cortex input, you're going to get
some kind of disturbance in somatosensory functions,
especially movements controlled by somatosensory
inputs, like when we form habits in response to touch.
We're using connections there in the putamen.
And you'll disturb those if you damage the part of the
putamen that's getting that input, and similarly motor
cortex and premotor cortex connections.
So when movement disorders occur, we're often thinking
about putamen function.
And similarly we can find parts of the striatum here
where the frontal eye fields project and the parietal lobe
areas that control eye movement project, the parts
that get input from the visual cortex.
Well, those tend to be in parts of
the head of the caudate.
So if you disturb those areas you get eye movement problems.
If you're in other parts of the head of the caudate, you
can disturb various cognitive functions because you're
disturbing areas that are getting prefrontal neocortex
connections.
You can disturb mood and emotions from, where
would you be there?
Would you be someplace in here?
Probably not.
You'd be in ventral striatum.
This would be from disturbances of the accumbens
or other parts of the ventral striatum.
So the separation of these different functional pathways
at some medical schools make a lot about sometimes they
divide it up very rigidly into these four or just maybe five,
it's a little bit arbitrary.
Because it's as many functions as you find in the neocortex.
You're going to find related functions in the striatum
because they're getting their major input from neocortex.
So you get many different functional pathways.
Now just to zoom in a little bit on the striatal neurons, I
just wanted to point out a couple of things here.
This is from another [? Brodall ?]
picture.
There are large neurons there.
In many parts of the brain, the interneurons with short
axons are small neurons, like in the thalamus.
The interneurons are small neurons.
In the cortex, the smallest neurons have short axons.
They're not the neurons that project down to the thalamus
or down to the brain stem or even long connections to go to
the transcortical connections.
They're little neurons that connect and [UNINTELLIGIBLE]
the intercortical column or to nearby columns.
But in the striatum, these big neurons, using acetylcholine
as a transmitter, are the interneurons.
They connect locally.
Whereas the neurons with the longer axons, which are
smaller, they use as their main neurotransmitter GABA,
inhibitory neurotransmitter, but they also
contain various peptides.
So for example, here's a type that contains GABA and
substance P. Another type contains GABA and
[? incaplar. ?]
But there's many other peptides, too.
There's up to 100 different substances that you can find
in neurons there.
So this is a vast--
This is just an example of a couple of them.
And it's showing dopamine axons coming in and contacting
all these cell types.
These are the dopamine axons coming from
the substantia nigra.
Or if we were more ventrally, it would be coming from the
ventral [UNINTELLIGIBLE].
And those axons go out to the globus pallidus and to the
substantia nigra.
So the pallidum, this globus pallidus, GPI and GPE, that's
for external and internal components
Now just pull back and look at a little bit of gross anatomy.
I want to know about where you get the [? lenta ?]
form nucleus is this lens shaped area.
There you see it there.
That is the putamen and the globus pallidus.
There's the caudate up there, the part that's cut off from
the rest by all these internal capsule fibers.
In this picture, they've cut a lot of it off.
That's actually the caudate clear up there.
And there's a little bit there.
But that probably would still be called putamen.
So here comes internal capsule, through it, caudate
up there, putamen down here.
And here it is in the drawing, caudate up there, putamen down
here, and then the globus pallidus.
Well, if we go out from that, you come to the claustrum, a
little extra layer of cells there below the
cortical white matter.
And then you're in the cortex of the insula.
That's the cortex buried in the sylvian fissure.
So if we're doing a dissection and we came through, in order
to get to the outer surface of the so-called [? lenta ?]
form nucleus, that is the putamen and globus pallidus,
we'd have to open up the sylvian fissure.
Just pry it open and we'd expose the buried cortex, the
island cortex, an island of cortex there.
At the bottom of that fissure, that's the insula.
You know what insula includes?
It includes the gustatory cortex, for example.
It's not as well known, actually.
But with the imaging methods now, they're getting a lot
more information about it.
And then if you scraped off the insular cortex there, you
would expose, after going through the claustrum, you'd
expose the surface of the putamen, this structure here
in the axon state.
And if you kept going, you would get to the
inner part for this.
It's like the outer part of the ice cream in
an ice cream cone.
When you go down to the part at the bottom of the ice cream
cone is the globus pallidus.
So what are these axons again coming
down through the striatum?
Internal capsule, they're coming mainly from neocortex.
There's also some axons coming from the striatum here, mostly
coming from neocortex.
What's on the other side?
What's all this?
What are those structures?
That's all thalamus.
And the peduncle, the axons continue.
You're beginning to see some structures usually included in
the midbrain there.
Well, we're going to talk about the various thalamic
cell groups pretty soon.
Next week we'll start doing that.
So we won't spend a lot of time on that now.
Let's just take a couple of pictures just to start getting
used to some of these human brain pictures.
And I've labeled this picture.
So I'm showing thalamus, two parts of the thalamus there,
several peduncle, outer boundary of the thalamus.
And it's joined with the fibers coming out of the
so-called white matter, which is black here, of the
hemispheres.
There's the hypothalamus.
We're already at the caudal end of it there.
You can tell by these little round globes, globe-shaped,
that those are the mammary bodies at the caudal end of
the hypothalamus.
OK, now if we follow neocortex around, notice that below the
neocortex the layers of cells, you find the white matter
where we have all the axons, until you get right in the
medial part.
And then suddenly it becomes very thick.
Well, where else did it become very thick?
Up in the front, the old basal core brain, there it's called
olfactory tubucal out here, and ventral striatum in there.
Here it's a similar thing.
But this is amygdala.
We're behind the basal forebrain.
We're out in the hemisphere here.
That's the amygdala.
So on this side, is that's the amygdala, we're at the very
anterior tip of the temporal lobe seeing amygdala.
If we went a little bit further caudal, we'd start
seeing hippocampus.
And in fact, this side is a little bit further back.
The amygdala's smaller.
And there's hippocampus.
It's cut in a funny way.
So it's difficult to make perfect sense of it without
knowing exactly how the hippocampus is shaped.
So this is just the same thing blown up just a little bit.
So one more thing here, here's these four brains to
illustrate the formation of the temporal lobe.
Here's a little rodent brain, a hamster or rat or mouse.
This cortex here hasn't expanded so much.
But the equivalent to that cortex there is down here in
the monkey.
It's here in the cat.
This is the formation of the temporal lobe.
So this cortex has extended, gotten big.
Remember cortex, it's a very simple genetic change.
To get more symmetric cell division
and the cortex expands.
It gets bigger.
And that's what's happened here.
So it's happened the most in human here.
This is all temporal lobe.
So the amygdala would be right in there, right in there.
And hippocampus would be in there.
So what happens to the internal capsule?
I can't remember if we did this before.
Here [? Nauda ?], he's pictured the dissection, where
he's followed the axons the lateral edge of the internal
capsule down through the striatum, and he's carved out
the putamen.
And he's exposed the whole [UNINTELLIGIBLE] peduncle
there, and he's pictured it, showing it how it goes down
and forms the pyramidal tract and the highbrain and down
into the spinal cord.
Well now imagine here, this is left hemisphere.
And I've said we've carved out the putamen.
And then we get to these axons.
What's on the other side of the axons?
Well, the rest of the striatum, the caudate nucleus,
so the caudate is on the other side of these fibers.
Well, follow that around.
What happens with the formation of
this temporal lobe?
What's just on the other side of these fibers here, so it's
medial, is caudal to the fibers back here and ventral
to the fibers down here.
So that's what happens to the caudate.
And if we made a section like this, we'd section
the caudate up here.
And we'd see the caudate medial to the axons.
Down here we would see the axons again.
And we would see the caudate below them.
Well, here's a horizontal section.
There you see the caudate there.
And you see, again, a piece of it there.
These axons they should show here, too.
These are the axons, the internal capsule, they way
they've cut them.
But that's the reason you get these funny pictures, the
caudate putamen with this long tail.
Because these are all in the space there in the middle.
These are axons to the internal capsule.
If you take the axons away, then you see that the whole
thing is continuous.
And they're the same cell types, same kind of structure.
So let's talk a little bit now more about the striatum and
Parkinson's disease.
I think it's an important topic in a neuroanatomy class
to talk a little bit about the views of doing transplants of
fetal nigra.
So we'll do that now.
So this will be last part of the striatum.
And we'll see how far we can get here.
The readings are about fetal nigra transplantation as a
therapy for Parkinson's disease, how they use brain
imaging to visualize living dopamine producing cells, and
then new nerve cells that are not transplanted but grow
normally in the brain.
We've already talked about the ones in the olfactory bulb
that happens in the hippocampal formation as well.
And I think when we covered the
hippocampus, I mentioned that.
So a little bit about fetal brain tissue transplantation,
the surgery and questions about that relate to what we
just talked about, the topography and the striatum,
first of all, how do you think they could--
If people with Parkinson's are missing dopamine axons coming
from the substantia nigra, which is
their biggest problem--
And there are other problems, too.
Norepinephrine is affected.
And we know less about the consequences of that.
Because the focus has been on the dopamine axons.
And the functional studies have indicated that that's of
major importance in Parkinson's symptoms.
These people progressively are losing the dopamine producing
cells of the substantia nigra.
And when that loss reaches about 80%, they
start showing symptoms.
Why didn't they show symptoms before then?
Well, remember this is a gradually growing lesion.
And because it's slow growing, the brain is adapting to it in
an interesting way.
You're getting a lot of collateral sprouting in the
remaining dopamine axons.
And they can compensate for the loss of the other cells
but only up to a point.
And then these remaining dopamine axons can only form
an arbor that's so big.
And then they can't handle it anymore.
You get to about 80%, only 20% of them left can't seem to do
the function.
Well, they don't replace with the therapy doing transplants
of fetal tissue that grow axons in the brain.
They don't put the tissue in the nigra that's showing the
degeneration.
Now in this case with rat you actually go in and make a
lesion of the nigra to produce the Parkinson's symptoms.
There are methods, though, of getting it to occur.
There are chemical treatments, too, you can use to get rid of
dopamine in cells.
Instead, they put the cells right into the striatum.
So I'm asking here, why is the topographic organization of
connections from the nigra to the striatum maybe not the
critical thing in treating it?
And the answer is that, if the dopamine is simply a modulator
that is controlling excitability of cells in the
striatum, the main thing might just be that
they get enough dopamine.
It doesn't mean that in the normal case there might be
some modulation where topography might be important.
But the idea is that if you just can get the dopamine
connections made, that might be enough to get function, get
improvement of function.
Because when you're treating human patients, your ultimate
goal might be to get everything back.
But if you can just get the major things back so people
can walk, for example, and move their arms without
shaking, that's a big improvement in
their quality of life.
So if you're going to use fetal cells--
And experiments were done on animals, especially rats,
before any of this was tried with humans.
They realized that they could keep substantia nigra cells
from a baby animal or fetal animal alive in a
tissue slice culture.
You can take a slice of the brain out and keep it alive in
the culture medium.
I've done that a lot for retina and [UNINTELLIGIBLE].
But this is done now for the nigra.
And if you have a good culture medium and you keep the cells
alive, the cells will start growing axons.
And these are axons using dopamine as a transmitter.
So the idea is just take them out, take a little chunk of
nigra out, put them right into the putamen, let them grow out
axons and form connections right there in the putamen.
Why would they do it in the putamen?
Well, because remember that's the part that's getting the
input from the sensory motor cortex.
And that's the area that is causing
these disturbed movements.
And often that's the part that's most affected earliest
in these Parkinson's patients.
So how would they know what age to use?
Well, they could make rough guesses by knowledge of when
the axons are forming.
And that's been studied a bit in humans
but mostly in animals.
But the best way was to do it experimentally.
So they took--
And of course, they didn't have complete control of when
they're getting the fetal tissue from humans.
Because these were aborted fetuses.
And it just depends on when the abortions occurred.
So they would get cells from the nigra of
those aborted fetuses.
And obviously it can't be very long.
If the tissue's dead for very long, the cells
will die in the brain.
So speed was pretty important.
So they got cells from fetuses of different ages and put it
in the brains of immunosuppressed rats.
And they found it to be a very good predictor of how cells
will survive in the human brain.
As long as they were immunosuppressed, the results
were a good predictor.
And then they could do histology later.
And they can stain them for tyrosine hydroxylase by
immunohistochemical procedures.
So at the top one here, the black there shows tyrosine
hydroxylase in cells.
And you can actually see the processes in the cells.
Tyrosine hydroxylase is an important enzyme in the
production of dopamine.
If they got the cells from a 41 day post-conception fetus,
they survived very well If they got it from a fetus 72
days after conception, they didn't survive very well.
So they did a lot of experiments like this and
[UNINTELLIGIBLE PHRASE]
on the ages when they got good survivors.
So now they knew the age of the fetuses they had to use.
And then when they started putting it in humans they had
several problems.
One was just how do you assess whether you even got survival
in the human brain.
They would inject flora dopa, which produced radiation
positron emissions only if the cells are a alive, of course.
So by using positron emission tomography, they could image
the living dopamine cells and find out, are these living
cells there in the putamen or not?
And there's a picture there in this paper, the
[UNINTELLIGIBLE] paper back in '96.
Or if the person died, and, of course, many of these people
finally did come to autopsy and they assessed them after
in the autopsy material.
They're usually doing this in pretty
advanced Parkinson's patients.
So it was inevitable that some of them were going to die.
And when they did, they would get the tissue and stain for
using tyrosine hydroxylase immunohistochemistry.
And if they looked in the region of putamen where they
had put implants--
And here you see evidence for a number of
different implants .
And I'll ask you why you think why did they have to put a
number of different implants in.
But anyway they could look at higher magnification here and
see a lot of dopamine containing axons
there in this putamen.
So the cells were certainly surviving and growing axons.
And if they went a long distance from where the
implants were, almost nothing.
So these axons were limited in how far they could grow.
And this just shows what I mentioned before that they
could make the grafts into the rats, striatum them, and
predict the survival.
This is in a rat.
This is in a human.
And they're similar enough in survival of the dopamine cells
Now, the problem caused by the large size of the human brain,
the nigra in the human fetus at the say 41 days after
conception is very tiny.
They can't get enough tissue to cover
very much in the striatum.
The problem is the axons don't grow very far.
But one thing when axons grow out into adult tissue--
Remember we talked about regeneration and the
problems with it.
You get such slow growth in the adult brain.
And these cells will grow like 60, 80 microns an hour.
And if you do the calculations, that's going to
take a long time to grow very far.
And they would grow about 10 times that fast if it were
fetal tissue they were growing in.
But these are adult tissues with a lot of
[UNINTELLIGIBLE].
So they didn't grow very far.
They could grow several millimeters.
But it's a big problem.
So they had to get multiple transplants, multiple fetuses,
to treat one patient.
and that's one of the big problems with this method.
It's very difficult to get all this tissue.
And for placement, they were putting it in the putamen
because they knew that was most important for the motor
functions that were disturbing the quality of life of these
patients the most.
It took a long time waiting for results.
They did get effects.
But it took a long time before they appeared.
But remember the axons were growing very slowly and
forming their connections.
Then they, of course, because the limited availability of
this material they thought of alternatives.
It was a company formed here in Massachusetts to
genetically alter pigs and make it so the tissue was
totally compatible with human so they could use xenografts.
I've not heard too much about that.
It didn't prove to be as successful as they'd hoped.
But they've tried non-neuronal cells.
For example, you can genetically engineer
fibroblasts.
You can get the fibroblasts and grow them up
from the same patient.
You can genetically alter them so they will produce dopamine.
That method has been tried.
Again, a lot of these methods work fairly well in animals
and then more difficult to apply to humans.
They've even tried implanting devices that
could release dopamine.
Where the biggest emphasis is been more
recently is on stem cells.
If they can produce the stem cells from the patient's own
body, manipulate them so they will differentiate it into
dopamine releasing cells, that would seem to be the optimal
way to get cells.
And what's happened to this?
First of all, they found that, except for patients that had
only mild symptoms when they came to this treatment, it was
not very successful.
It didn't work all that well unless they
weren't as far along.
And I've given you the citation here.
[? Olino, ?]
who had done some of experimental work with
animals, was involved in this double blind controlled trial
of the fetal nigra transplantation.
And it was very discouraging.
And that led people, especially for these very
severely disturbed patients, to use
other forms of treatment.
And if you go online and look under deep brain stimulation
for Parkinson's disease, you will find reports.
And you will see how they talk about the best sites.
Do they stimulate the ventral thalamus or the subphlanic
nucleus in globus pallidus?
These are the areas they've tried.
And stimulating often was very successful at reducing the
symptoms of Parkinson's.
And interestingly, they don't have to
continuously stimulate.
The effects of the stimulus can outlast the stimulation.
And then here at MIT in Rudy Jaenisch's lab, they have used
stem calls to treat Parkinson's
conditions in rats.
And they've done that successfully just last year.
I don't know what happened to my--
Probably it's later on.
I actually quote the news article.
So you can take a look at that.
And the beginning of the next class I'll talk a little bit
about the new neurons that appear naturally in brains.
We'll mention the the stem call work again.
Then we'll be off into neocortex.
And I will try my best to finish that chapter
so I can post it.
Because we're going to do a dissection on Monday.
And I'm just going to get you to read the chapter.
And then we can go on into the anatomy of the neocortex and
thalamacortical connections.