MARIAN DIAMOND: Let's continue
with our nervous system,
our neurohistology.
And just-- we're on the axon.
And two structures that are
within the axon, neurotubules
and neurofilaments, are
important because they
give structure to the axon.
If a process has to
be so long, these
provide structure
and can help direct
what we call axoplasmic flow.
The cytoplasm within the axon
is flowing from soma to synapse.
So these provide-- well, we
won't put "provide" there.
Used that word before.
They direct axoplasmic flow.
Now, let's continue with our
myelin that we had introduced.
Myelin is formed from
two kinds of cells.
In the PNS, myelin
is formed by what?
Schwann cells.
Right.
Schwann cells,
after Mr. Schwann.
In the CNS, myelin
is formed from what?
Oligodendrocytes.
Right.
I'm not going to write "formed"
again, but oligodendrocytes.
So a Schwann cell, as it--
let's put our typical
neuron in here.
And this is our axon.
We'll see that the Schwann
cell-- many Schwann cells
can myelinate a single axon.
And we'll put a few in here.
They wind around.
So this will represent the
nucleus of a Schwann cell.
Here's another one.
Just trying to show that the
myelin is laid down in layers.
Another nucleus.
So these are examples
of Schwann cells
that have wrapped
around and formed.
So, many Schwann cells per axon.
Now, the distance
between the Schwann cells
is a very important area.
On the nerve fiber here, this
distance which has no myelin,
this is referred to as
the node of Ranvier--
node of Ranvier.
And there's no myelin.
It's just the gap
between myelin cells.
And it's important with the
conduction of the impulse,
because the impulse will go
between nodes of Ranvier.
So the impulse--
they call it jumps--
between nodes of Ranvier.
So we've already said the
more myelin, the more rapid
the impulse.
Now with the oligo, one oligo
can myelinate many fibers.
Quite a different picture.
So the other formation of myelin
comes from oligodendrocytes.
And one oligo, as we call
them, working in the field,
can myelinate many axons.
So when we get these
demyelinating diseases,
you want to be
aware that there are
two kinds of cells,
two kinds of processes
by which they myelinate.
Now, let's-- does anybody know
anybody with a demyelinating
disease?
What's the worst nerve you
want to get demyelinating?
What's one I just wrote on the
board-- on the other board?
Phrenic nerve.
Why is it the worst?
There goes your diaphragm.
There goes your breathing.
Right.
So you can get demyelination
throughout many areas,
but catch it in the
phrenic and that's drastic.
So let's say a word
about dendrites then.
And we said you could
have one dendrite
or you could have thousands.
Just think of the receptive
surface when you have
thousands, the
integration that has
to go on within a single cell.
Now, dendrites can have--
increase their surface area by
having what are called spines.
Have you heard of
dendritic spines?
Dendritic spines increase--
I'll show you pictures of them--
the surface area
of the dendrite.
They're quite fascinating
little structures.
If I have a dendrite, then I'll
have a little spine come out.
This will represent
a dendritic spine.
As innocuous as it
seems, it can receive
as many as nine synapses on it.
An area of very rich integration
on a dendritic spine.
I'll show you an EM--
electron micrograph--
with nine synapses.
Can have-- we'll put one or
many synapses on a spine.
So they're not just
innocent little bystanders.
They are very active.
In fact, they can change
their structure in 30 seconds.
And I called Floyd Bloom,
who was head of science
before, just a week
ago, just to ask
him do we know anything more
about when they disappear
if they leave a molecular
configuration there
or whether they lose it and
have to start from scratch.
But spines are, as some
people say, very important.
And they are different
shapes and sizes.
But they're a dynamic
part that most people
aren't aware of in your
lower biological courses.
But when you go along, you'll
get acquainted with them.
Now, we want to
look at glial cells.
Can I take this off?
Glial cells.
Briefly, we can
say that they are
the metabolic and structural
support cell of the nerve cell.
Metabolic-- if somebody
just asks what are they--
metabolic and structural
support cell for the neuron.
They need each other.
There are what we
call macroglia.
Macro-- large-- macroglia.
Macroglia.
And microglia.
Microglia.
Types of macroglia
will be astrocytes.
Astrocytes.
They look like stars.
Astrocytes.
Astronomy.
And other kind of macroglia
will be the oligodendroglia.
Oligodendroglia.
Now the macroglia are
derived from ectoderm.
For those who haven't
had any embryology,
there are three germ layers from
which all tissues of the body
are derived.
And it's interesting
when you're trying
to find out functions
of cells, do they all
have the same derivative
or are they different?
So this is just an embryo.
All tissues from
either ectoderm--
ectoderm-- mesoderm,
or endoderm.
Nerve cells come from
ectoderm, and so do macroglia.
Microglia come from mesoderm.
If microglia come
from mesoderm, how
do they get into the central
nervous system, which
is an ectodermal derivative?
The microglia will migrate
from the bone marrow--
you know what bone marrow is--
along blood vessels to the CNS.
So, what we'd like to do
then is look at astrocytes.
Why do you need astrocytes?
What are they doing for you?
How are you going to tell
an astrocyte from an oligo?
So astrocytes-- so as
we said, star shaped--
so they'll have all processes.
There are different
kinds, so it's sort of
difficult to do a single kind.
But they've got all
these processes.
This is a cell body.
Astrocytes-- many processes.
And all are alike.
Different from a nerve
cell, where you've got
dendrites and axons.
Many processes, and all alike.
Now, why do you have astrocytes?
What are their functions?
First very important
function, they
initiate the formation of
the blood-brain barrier.
Initiate the formation.
They do not make up the
blood brain barrier.
They initiate the
formation of it.
Very important distinction.
So let's put it here
so we have more room.
Initiate the formation of
the blood-brain barrier.
What in the world is that?
Again, we abbreviate it.
Will be tight junctions
between the endothelial cells
of the capillaries in the brain.
Not everything that the
rest of the tissues get
does the brain want.
It wants to limit
and be able to choose
what it wants to come in.
And so we have a
barrier, and the barrier
equals the tight junction
between endothelial cells
in brain capillaries.
Other capillaries don't
have tight junctions.
What else?
The astrocytes help form
the pial-glial membrane.
Pial-glial membrane.
They help form
pial-glial membrane.
Now what in the world is that?
We talked about the
membranes that protect
the central nervous system.
Well, the pia is the one
that's adherent to the CNS.
So briefly, if we do this--
and just call this brain--
we'll have a pial membrane just
adherent to the brain tissue.
So this is pia.
What does pia mean?
What's its full name?
Pia mater versus dura mater.
Pia is gentle.
Gentle mother.
And now then, we'll have--
let's just blow up an
astrocyte inside the brain.
And it will take
its process over
and put it adjacent to the
pia, called a foot process.
Another astrocyte, come
over, put a foot process.
So the pial-glial membrane--
astrocytes in pink-- is the
foot process of astrocyte
and the pial membrane.
And this surrounds--
this membrane
surrounds the whole CNS,
spinal cord and brain.
So it's for protection.
You get an ice pick that
stabs through your brain,
immediately these glial
cells will multiply and form
scar tissue.
So it's for protection.
Very important, though
it causes problems
when you want regeneration
because you've
got the scar forming.
It's very important to protect.
Now why else do we
have astrocytes?
Every time your nerves fire,
they liberate potassium.
They pick up that
excess potassium.
So after neuronal
firing, the astrocyte
picks up excess potassium.
I'll write it out so
it's not confusing.
Loads and loads
of functions here.
Do you ever wonder, those who've
studied the nervous system
have seen that, when a synapse
fires and the transmitter
goes across-- why
doesn't it go sideways?
There's nothing on the
sides of the synapse.
You have astrocytic feet.
They prevent the transmitter
from going sideways.
So, we could go on and on and
on with the functions here.
Very dynamic-- have you ever
known you had astrocytes?
Ever thought about them?
No.
They are very precious.
Astrocytoma.
Has anybody had anybody who's
had a tumor of astrocytes?
Yeah?
The glioblastoma multiforma.
Good.
Because once it's diagnosed,
you have no more than a year
to live.
It's really a deadly-- brain
tumors are primarily gliomas.
They're not neuromas.
So glial cells--
don't shun them.
They are terribly important.
Glioma-- that's tumor of glia.
No.
I get off on tangents.
But my brother had a
glioma, an astrocytoma,
and the first thing the
doctor said, did he smoke?
And I said yes.
It just sort of fit,
just like we learned
with cancer of the lung.
Right?
Gliomas too, with smoking.
You never hear about
them because people
don't know glial cells.
So, anyhow, you have
lots of things to say.
Oh, one of the most
important here--
I'd better put it,
because it is important.
They serve as a scaffolding--
scaffolding-- for neural
migration during development.
Very important.
If cells don't migrate--
aren't you lucky.
All your cortices--
all your cells
have migrated into position.
Major function just to get
them in the right place.
You get a flu virus at a
certain time during gestation,
you could knock them off course.
It's amazing.
Such a dynamic system.
All right now,
we'll go to oligos.
We've already said what
oligos due primarily.
We don't know much
about oligos' functions,
other than forming myelin.
But I will mention one thing.
Oligo functions--
repeat, repeat, repeat.
Form myelin.
But also, they serve
as satellite cells
to blood vessels and neurons.
Serve as satellite cells to
blood vessels and neurons.
Now we're not quite sure
what they're doing there,
but you see them
there all the time.
What they're exchanging
with those blood vessels,
what kind of nutrients,
what kind of ions, whatever.
But that's a major cell
and it has that position.
Myelin, sure.
We know.
Then I mentioned the microglia.
I'll say one more
word about them.
We said they were mesodermal.
But we didn't say anything
about their function.
They're very small
until activated,
until there's an injury.
Until activated by injury.
They're just sitting there,
sort of waiting for an accident
to happen.
But when it does, then
they become phagocytes.
Become phagocytic.
What popular disease with
aging are nerve cells
degenerating today?
Alzheimer's.
Many microglia are present
in Alzheimer brains.
Then, there are lots
of other glial cells.
Little by little,
we'll encounter them.
But these are the major--
do you like glial cells?
Do you?
I don't think this
little fellow that I'm
talking to right here does.
Do you?
You're not interested
in glial cells.
Do you like neurons?
Yeah.
OK.
Well, it's my job
then, as a teacher,
so that you become
acquainted with both.
Because one without the
other is not very useful.
And that's a problem with many
of our theoretical people.
They go only to
neurons, and they
don't realize they should
know the glial cells as well
as the neurons.
Respect to them, I mean.
I'm not condemning them.
But it's so important.
So now, we want to
look at the synapse.
And many of you have
probably had your synapses
in basic courses.
But for those who
haven't, because there
are quite a few
who haven't, this
is the structural and functional
unit of the nerve cell.
This is where the
dynamics takes place.
Where the variation is.
All kinds of neurotransmitters.
So, synapse-- structural
and functional unit
of the nervous system.
So, we're going to
follow an impulse
down an axon to a dendrite.
Let's put them in here,
sort of in large form.
This is the end of an axon,
the beginning of a dendrite.
Axon.
Dendrite.
And this junction between
the two is our synapse.
And we'll first follow
down on electrical impulse,
because sometimes you can--
somebody wants to know
how a nerve works,
you can use your arms and
your hands very readily.
This would be the
main axon coming down.
It's all electrical down here.
As it gets to the terminals,
then it's chemicals.
Chemicals cross
the gap, stimulate,
and you have the electrical
impulse going on.
So we're going to see, then,
how the electrical impulse is
coming down.
So one is the electrical
impulse coming down the fiber.
Down axon.
And then we come
to what's called
the presynaptic terminal.
If this is my
synapse in here, this
is my presynaptic terminal.
And the presynaptic terminal
is filled with little packets
of neurotransmitter vesicles.
So we're going to
put in vesicles.
So three will be vesicles
of neurotransmitters.
Neurotransmitters.
E- R-S. T-R-A-N-S-M-I-T-T-E-R-S.
The neurotransmitters are formed
in the presynaptic terminal.
Formed in presynaptic terminal.
They also contain
neuromodulators.
For some transmitters
to work, they
have to be in a
certain environment.
So you have the chemicals
that modulate the environment
so the neurotransmitters
can work.
So, we also have vesicles
of neurotransmitters
and neuromodulators.
When we first started this
work, there were maybe five
known neurotransmitters.
Now there are 100, when you
combine all the neuromodulators
with the neurotransmitters--
the synapse is so complex now.
Used to be so simple, like
everything else in life.
All right.
So we have neuromodu-- the
neuromodulators are formed
in the soma of the nerve cell.
How do they get down to
the presynaptic terminal?
What conveys them down?
The axoplasmic flow.
You've got to have some
transportation from the soma
to the terminal.
So that's why you have
this flowing axoplasm.
Once you've seen people collect
axoplasm out of a giant squid,
you never forget it.
Because there's so much
axoplasm in that big neuron.
It just drips off.
So you know that it's
a dynamic structure.
So, now what's going to happen?
We've got our vesicles.
They're sitting there.
We've got to activate them,
get them close to the terminal
here.
So we have-- when the electric
current is coming down,
we have calcium ion out here.
So four will be coming in here.
And four-- can I take
off this or should
I go to the other board?
You're finished with this side?
Are you?
Great.
Keep it close, if I can.
I mean, just think-- for every
movement, every eye blink,
all of this is taking place.
There's something now, right?
All right, so four
represents a calcium ion.
When the electrical
impulse comes down,
the calcium ion comes
into the terminal
and sets up a substructure
to guide the vesicles down
to the membrane.
So calcium enters
presynaptic terminal, sets up
substructure to guide vesicles
to presynaptic membrane.
And once they get there, then
they fuse with the membrane
and discharge their contents.
Got some contents here.
Just make it neurotransmitter.
And calcium enters,
sets up the substructure
to guide the vesicles to
the presynaptic membrane.
To release the
neurotransmitter, they
open up and put the
neurotransmitter
in the synaptic cleft.
This is my synaptic cleft.
And what are they going to do?
Well, they've got to
react with receptors
on the postsynaptic membrane.
Receptors on
postsynaptic membrane.
And will open ion channels.
To open ion channels.
And that's their function.
That's what the
neurotransmitters do--
open those channels.
And when the channels
open then, ions rush in.
Let's just take calcium ion.
Can go in to my postsynaptic
ending or terminal to act on--
what are they going to act on?
Enzymes or genes.
Say they'll act on genes
for protein formation--
we can just come out for those--
for protein formation.
And what are we going
to do with that protein?
We can build a bigger terminal
to enlarge the terminal.
We find with our
enriched environments--
when our rats go
to school, they get
bigger postsynaptic terminals.
And when they
don't, they shrink.
You see why I work so
hard for yours to get big?
Because the bigger those
postsynaptic terminals,
the better the learners
those rats are.
If they can do
it, you can do it.
Right?
So for protein formation--
for neuronal structure is what
we'll just put in general.
Neuronal structure.
So, that gives you an idea
of how a synapse works.
But now, you say, what's going
to happen to this transmitter
that's up here in the cleft?
We don't want it to keep firing.
So it can break down.
The transmitter and
the cleft can break--
or it can recycle and go back
into the presynaptic terminal.
So neurotransmitter in
cleft can break down.
The technical term
is to hydrolyze.
Hydro-- hydrolyze.
Or can recycle.
We're all aware of how important
recycling is in today's world.
So, how is it going to recycle?
How's it going to get back
into the presynaptic terminal?
For recycling, the
neurotransmitter
will hop a carrier.
There are some carriers
in that presynap--
in that synaptic cleft.
Neurotransmitter--
what does that mean?
Are you OK?
Well, communicate with me.
If you're not OK,
tell me where to stop.
All right?
It's all basic.
It's happening in your system
every second of your existence.
The neurotransmitter
hops on a carrier.
And the carrier takes it back
to the presynaptic terminal.
Back to presynaptic terminal.
That's presynaptic--
let's write it better--
terminal.
Now, why do we stress this?
Thank you.
Good, I can make my point.
How many of you
have taken cocaine?
[LAUGHTER] Just want
to see if you're awake.
If there's an empty
carrier in there,
and you're taking
cocaine, cocaine
will hop on that carrier
and block the re-uptake
of the transmitter dopamine.
It's dopamine that
has these carriers.
So, you don't want
to take cocaine.
Oh boy, sorry.
Sometimes the erasers work
and sometimes they don't.
So, dopamine hops
carrier if available.
Cocaine hops carrier
if available.
So, what happens if the
cocaine hops a carrier,
then the dopamine has none?
So the dopamine stays in the
cleft and can keep firing.
Give you a high.
Soon wears out.
Needs more.
All right, let's
look at some slides.
This is a picture
we showed last time,
but you hadn't had the myelin.
So, let's say, if
you're shown this slide,
are we in the CNS or the PNS?
PNS.
Good for you.
Because you've got your
single Schwann cells here.
You've got the node of Ranvier.
When you're studying
electrophysiology
you'll see the response
at the node of Ranvier.
We said saltatory conduction
goes between nodes of Ranvier.
But these are Schwann cells
that have wrapped around,
forming myelin.
Myelin consists of a lipoprotein
within the Schwann cell.
It's in segments.
Next one.
This is just to show
dendritic trees.
The variation we
showed last time.
But you can appreciate
now how many
synapses can occur for that
single cerebellar cell to fire.
Isn't that amazing?
In the next one, now these
are dendritic spines.
You may do a preparation
with this method,
and you'll say, well look
at all the precipitant
I have on my dendrites.
That's not precipitant.
Those are direct little spines,
each one receiving synapses
to the main fiber.
Terribly important.
And the next one.
I'll say when
Francis Crick first
thought he's coming
into the nervous system
to get his second
Nobel Prize, he
was going to work on spines,
because he thought that's where
memory formation was.
But if they're changing
in 30 seconds--
see, you need to know
your neuro anatomy, right?
Here is a spine from
the electron micrograph.
Here's a synaptic terminal
with all the vesicles,
all the mitochondria.
Here is a synaptic
terminal, all the vesicles.
There, presynaptic terminal,
postsynaptic terminal.
Here's another one here.
These are all mitochondria.
But you can count nine
synapses on a single spine.
Next one.
Next one, please?
I think we had that one.
These are astrocytes.
These are what we call
protoplasmic astrocytes.
There are all kinds.
It's got this film around it.
That's natural.
It's got many processes.
And somebody showed,
on the front cover
of Scientific American
once, that all of these
form a syncytium.
They're all connected.
I've wondered with
astronomers, are all stars
connected somehow?
But the astrocytes of
the brain supposedly are.
Next one.
And these are oligos.
Oligo means few.
So few branches.
Here's an oligo.
Quite different
from the astrocyte.
And the next one.
And this just shows
many of the things
that an astrocyte can do.
Here's an astrocyte.
Here's a Schwann cell--
whoops, sorry-- Schwann
cell on a fiber.
Here's a Schwann cell.
Here's a node of Ranvier.
To prevent things
from leaking out here,
there's an astrocytic process.
Here's a synapse.
With my synaptic junction,
here's an astrocytic process.
These are the
ventricles, the channels.
These are ependymal glia.
Here is an astrocytic process.
We should have
pial-glial out here.
Here's an astrocytic process.
Here's an astrocyte around
the blood vessel, on the soma.
They're everywhere.
You don't want an
astrocytic tumor.
And the next one.
Here's an artist's rendition.
Here's the spine.
Here's a presynaptic terminal.
Losing the myelin.
Cut it open, here's
our synapse--
presynaptic terminal,
postsynaptic terminal.
Here's our myelin.
Myelin stops before it gets
down to the presynaptic terminal
and expands, full of vesicles.
And the next one.
Next one, please.
And this just shows how
an electrical-- this
is how synapses grow
stronger with use.
You have the electrical
impulse coming down.
Here's your
presynaptic terminal.
Here are your vesicles
filled with transmitter.
The calcium will run in.
These are glutamate.
So that you've
heard of glutamate.
It's the most common
neurotransmitter in your brain.
So it's here.
You get calcium coming in.
These will march right down
to the presynaptic membrane,
pour out their contents,
open a channel.
Calcium rushes in,
can activate enzymes,
alter protein composition of
the synapse, switch on genes,
and, of course, continue with
the impulse down the fiber.
But releasing
retrograde messenger--
probably nitric oxide--
a man at UCLA got the
Nobel Prize for that one.
He drives his yellow Porsche,
and his license plate
says Nobel.
Just to let you know.
I want you to
smile a little bit,
because sometimes
this gets heavy.
And that way you can relax.
That there's always a little
story behind everything.
Next one.
And this shows-- what's this?
Oh, here's anisyl
everywhere but here.
Axon hillock.
That's an axon coming
off a nerve cell.
Next one.
These are an artist's rendition.
Here-- all anisyl
substance everywhere,
dendrites, but not in an axon.
These are all glia
surrounding nerve cells.
Next one.
Next one, please.
And this just shows
you, when you were born,
you had few dendrites.
But look at a two-year-old.
Isn't that amazing?
No wonder they're so
difficult to deal with.
But it just lets you know
how important dendrites are.
We'll stop there.
