Neural cells work with all the other cell types of the body to produce the amazing range

of functions of
the nervous system, including consciousness, social interactions, cognition, emotion, movement,
sensory perception, and regulation of other functions, such as circulation, respiration, and digestion.
Neural cells are divided into two big categories.

The first are neurons, which were traditionally called nerve cells. And the second are glia. Now, these
can also be called neuroglia or glial cells. That all means the same thing. Neurons are named from a
Greek word for nerve, while glia are named from a Greek word for glue, because they were once
thought to do little except glue neurons together. The structure of the nervous system is divided into
two main parts. The first part is mainly made up of the brain in the head and the spinal cord in the spine.
And this part of the nervous system is called the central nervous system.

The other part of the nervous system is called the peripheral nervous system. And that's made up
mostly of nerves, these long, stringy structures that come out of the brain and the spinal cord. And they
go all over the body, like down into the arms, and down into the legs, and into every part of the body.
And we'll cover a lot more in detail about neuroanatomy in other videos. But I just need to bring up the
central and peripheral nervous system because the neural cells are divided up differently amongst the
different systems. Calling neurons nerve cells is a little problematic because these structures in the
peripheral nervous system called nerves are made up of neurons. But they also contain glial cells. And
they contain a number of other cells that aren't neural cells at all.

However, you'll often hear people refer to neurons as nerve cells because that was the traditional name
for them. Neurons are found both in the central nervous system, the brain and the spinal cord, and the
peripheral nervous system, in the nerves. But the different types of glial cells are found only in one or
the other. Most neural cells are derived from populations of cells called neural stem cells or neural crest
cells. And both of those cell types arise early in development in the part of the embryo called the
ectoderm. Most neurons and glia found in the central nervous system are derived from neural stem
cells, while most neurons and glia found in the peripheral nervous system are derived from neural crest
cells.

Now, we'll go into a lot more detail about what neural stem cells are and neural crest cells in other
videos, when we cover development of the nervous system. Most types of both neurons and glia share
some structural features of the way their cell is shaped. Most of them have a main part to their cell
called the soma or the cell body that contains the nucleus and most of the organelles. Coming out of the
soma, most of these cell types have processes, long, thin extensions that come out of the soma. And the
processes of the different neural cells vary in number and in length, in thickness, and degree of
branching, because some of them will be unbranched, and some of them will have processes that
branch, sometimes a little and sometimes a lot. They will also vary a lot in the terminal structures at the
end of their processes and the function of these structures and the processes. The function of neurons is
to process and transmit information.

And the function of glia is to support them in a variety of ways. There are many structural and functional
types of both the neurons and the glia. And there are large numbers of these cells making up the
nervous system. There are billions of neurons that form trillions of connections in the adult human
nervous system. And there even more glia than there are neurons. In subsequent videos, we'll go over
the most common glia, which are astrocytes, microglia, ependymal cells, oligodendrocytes, and
Schwann cells. There are also less common glia, such as satellite cells and olfactory and sheathing cells.
But we'll just go over the most common types here.

We could have a debate about what the most interesting cell in the human body is, but I think easily the
neuron would make the top five, and it's not just because the cell itself is interesting. The fact that it
essentially makes up our brain and our nervous system and is responsible for the thoughts and our
feelings and maybe for all of our sentience, I think, would easily make it the top one or two cells. So
what I want to do is first to show you what a neuron looks like. And, of course, this is kind of the perfect
example. This isn't what all neurons look like. And then we're going to talk a little bit about how it
performs its function, which is essentially communication, essentially transmitting signals across its
length, depending on the signals it receives.

So let's say I have a neuron. It looks something like this. So in the middle you have your soma and then
from the soma-- let me draw the nucleus. This is a nucleus, just like any cell's nucleus. And then the
soma's considered the body of the neuron and then the neuron has these little things sticking out from it
that keep branching off. Maybe they look something like this. I don't want to spend too much time just
drawing the neuron, but you've probably seen drawings like this before. And these branches off of the
soma of the neuron, off of its body, these are called dendrites. They can keep splitting off like that. I
want to do a fairly reasonable drawing so I'll spend a little time doing that. So these right here, these are
dendrites. And these tend to be-- and nothing is always the case in biology.

Sometimes different parts of different cells perform other functions, but these tend to be where the
neuron receives its signal. And we'll talk more about what it means to receive and transmit a signal in
this video and probably in the next few. So this is where it receives the signal. So this is the dendrite.
This right here is the soma. Soma means body. This is the body of the neuron. And then we have kind of
a-- you can almost view it as a tail of the neuron. It's called the axon.

A neuron can be a reasonably normal sized cell, although there is a huge range, but the axons can be
quite long. They could be short. Sometimes in the brain you might have very small axons, but you might
have axons that go down the spinal column or that go along one of your limbs-- or if you're talking about
one of a dinosaur's limbs. So the axon can actually stretch several feet. Not all neurons' axons are
several feet, but they could be. And this is really where a lot of the distance of the signal gets traveled.
Let me draw the axon. So the axon will look something like this.

And at the end, it ends at the axon terminal where it can connect to other dendrites or maybe to other
types of tissue or muscle if the point of this neuron is to tell a muscle to do something. So at the end of
the axon, you have the axon terminal right there. I'll do my best to draw it like that. Let me label it. So
this is the axon. This is the axon terminal. And you'll sometimes hear the word-- the point at which the
soma or the body of the neuron connects to the axon is as often referred to as the axon hillock-- maybe
you can kind of view it as kind of a lump. It starts to form the axon. And then we're going to talk about
how the impulses travel. And a huge part in what allows them to travel efficiently are these insulating
cells around the axon. We're going to talk about this in detail and how they actually work, but it's good
just to have the anatomical structure first. So these are called Schwann cells and they're covering-- they
make up the myelin sheath. So this covering, this insulation, at different intervals around the axon, this
is called the myelin sheath. So Schwann cells make up the myelin sheath. I'll do one more just like that.
And then these little spaces between the myelin sheath-- just so we have all of the terminology from--
so we know the entire anatomy of the neuron-- these are called the nodes of Ranvier. I guess they're
named after Ranvier. Maybe he was the guy who looked and saw they had these little slots here where
you don't have myelin sheath. So these are the nodes of Ranvier.

So the general idea, as I mentioned, is that you get a signal here. We're going to talk more about what
the signal means-- and then that signal gets-- actually, the signals can be summed, so you might have
one little signal right there, another signal right there, and then you'll have maybe a larger signal there
and there-- and that the combined effects of these signals get summed up and they travel to the hillock
and if they're a large enough, they're going to trigger an action potential on the axon, which will cause a
signal to travel down the balance of the axon and then over here it might be connected via synapses to
other dendrites or muscles. And we'll talk more about synapses and those might help trigger other
things. So you're saying, what's triggering these things here? Well, this could be the terminal end of
other neurons' axons, like in the brain. This could be some type of sensory neuron. This could be on a
taste bud someplace, so a salt molecule somehow can trigger it or a sugar molecule-- or this might be
some type of sensor. It could be a whole bunch of different things and we'll talk more about the
different types of neurons.

Neurons in adults have a soma. It's also called a cell body-- soma. And they have processes called
neurites, which are divided into dendrites and axons. Dendrites are usually short, branched processes
that are often covered in small spines that increase their surface area and perform some other
functions. So these are dendrites. And then the other neurite they have is called an axon, which is
usually long and unbranched until it reaches its end. So this is the axon. The area where the axon leaves
the soma is called the axon hillock. The axon may be short or it may be very long, up to one meter or
more.

And it usually is unbranched for most or all of that length, until it gets to the end, in these structures,
which are called axon terminals. And at this point, it will often branch and create multiple axon
terminals. The first part of the axon is called the axon initial segment. Or it's also called the trigger zone.
And we'll get into the reason for that in the next video. Axons can be so long that they are dependent on
systems that transport substances from the soma, which contains most of the organelles, to the axon
terminals, and vice versa. Things have to be transported both directions. And the axon is dependent on
those systems. Large axons are usually wrapped in a sheath of a material called myelin. And axons that
have a myelin sheath have little gaps between these segments of myelin call nodes of Ranvier.

So the sheath I've drawn in yellow is the myelin, each of these little segments of sheath here. And these
gaps that regularly interrupt the sheath are called nodes of Ranvier, these little gaps in the myelin
sheath. The axon terminals will come very close to the target cells of the neuron. And I'll just draw it
here. So these are the target cells. And these targets cells may be another neuron, they may be a muscle
cell, or they may be a gland cell. A few neurons even have axons that terminate on capillaries, to secrete
substances called hormones into the bloodstream. The place where an axon terminal comes close to
touching the target cell is called a synapse. This is a pretty typical structure for a neuron. But there are
multiple structural types of neurons, each of which can be further divided into subtypes. So let's go over
some of the big categories of structural types of neurons.

In the central nervous system, neurons start as neural stem cells, which turn into most of the cell types
of the central nervous system. And these neural stem cells then differentiate into cells called
neuroblasts. And don't worry about the details here. Because we'll go into a lot more detail in other
videos on development of the nervous system. But neural stem cells and neuroblasts look pretty similar.
They're basically just shapeless cells without processes. Neural stem cells can become almost any neural
cell of the central nervous system, while neuroblasts can only become neurons. Neuroblasts will then
migrate away from the neural stem cells to the location that their somas will have after development.
Neuroblasts then extend a process, which is an axon, toward their target cell. And that axon is tipped
with this structure called a growth cone-- growth cone. The axon growth cone follows guidance cues in
the environment until it reaches the target cell of the neuron.

A similar process occurs for neurons in the peripheral nervous system. But the original and the migrating
cells for those neurons are neural crest cells, instead of neural stem cells and neuroblasts. Neurons at
this stage have only one process, which is an axon. So they are now called unipolar neurons-- unipolar.
That's the structural type of this neuron because there's one pole to the cell, one process giving a sense
of direction on this otherwise shapeless cell. Unipolar neurons are present in humans, mainly during
development. The next structural type of neuron has a soma. And it has one axon. But it also has one
dendrite. So since this structural type of neuron has two processes, or two poles, it's called a bipolar
neuron-- bipolar.

The next structural type of neuron has a soma, just like the others, and one axon. But it has multiple
dendrites. And so since it's going to have multiple poles, it's called a multipolar neuron-- multipolar. And
this is the most common structural type of neuron in adult humans. The last big category of structural
types of neurons is a little different. It has a soma, like all the rest. And then it has one a short process
coming out of the soma, that then divides into two long processes going in different directions. And
these are both axons. The axon bringing information in from the periphery is called the peripheral axon.
And the axon bringing information into the central nervous system is called the central axon. The very
end of the peripheral axon acts a lot like dendrites do on the other structural types of neurons. And we'll
start to go over the function of dendrites and axons in the next video. And then this part of the
peripheral axon near the end is the axon initial segment, where the trigger zone, just like this part is on a
multipolar neuron close to the soma.

And just like in these neurons where this is the trigger zone, and then the end of the axon has the axon
terminals, in this type of neuron this is the trigger zone of the axon. And then the axon terminals are all
the way at this end of the central axon. So this type of neuron has a big, long, funny name. It's called a
pseudounipolar neuron-- pseudounipolar. And the reason is that it's kind of, sort of like a unipolar
neuron, with only one process coming out of the soma. But that little short process immediately splits
into these two long axons. So it's really a different shape than the unipolar neurons.

The function of neurons is to process and transmit information. Without input, most neurons have a
stable electrical charge difference across their cell membrane, where it's more negative inside the cell
membrane and more positive outside the cell membrane. And we call this the resting membrane
potential or just resting potential for short. And this resting potential is really how the neuron is going to
be able to be excitable and respond to input. And I think of this as similar to loading a gun by putting a
bullet in it.

Neurons receive excitatory or inhibitory input from other cells or from physical stimuli like odorant
molecules in the nose. Input information usually comes in through the dendrites. Although less often,
it'll come in through the soma or the axon. The information from the inputs is transmitted through
dendrites or the soma to the axon with membrane potential changes called graded potentials. These
graded potentials are changes to the membrane potential away from the resting potential, which are
small in size and brief in duration, and which travel fairly short distances. The size and the duration of a
graded potential is proportional to the size and the duration of the input. Summation, or an adding
together of all the excitatory and inhibitory graded potentials at any moment in time occurs at the
trigger zone, the axon initial segment right here.

This summation of graded potentials is the way neurons process information from their inputs. If the
membrane potential at the trigger zone crosses a value called the threshold potential, information will
then be fired down the axon. So I like to think of this process of summation of the excitatory and
inhibitory graded potentials at the trigger zone as analogous to the trigger of a gun. In fact, that's why
it's called the trigger zone. I think of the graded potentials as being like the finger on the gun, that may
be squeezing a little harder or relaxing. But once the trigger of the gun is pulled back past a certain
threshold distance, a bullet will be fired down the barrel of the gun, just like if the membrane potential
of the trigger zone crosses a threshold value, information will be fired down the axon. The way
information is fired down the axon is with a different kind of change to the membrane potential called
an action potential.

An action potential is usually large in size and brief in duration. But it's usually conducted the entire
length of the axon, no matter how long it is, so that it can travel a very long distance, just like a bullet
usually has no trouble making it down the barrel of the gun. And like a bullet traveling through the
barrel of a gun, action potentials tend to travel very quickly down the length of the axon. Action
potentials are different than graded potentials because they're usually the same size and duration for
any particular neuron, as opposed to the graded potentials, whose size and duration depends on the
size and the duration of the inputs.

Action potentials are conducted faster along larger axons, axons with a larger diameter, and along axons
that have a myelin sheath, that I've drawn in yellow here. When an action potential reaches the axon
terminals at the end of the axon, information will then cross, usually a small gap, to the target cell of the
neuron. And the way this happens for most synapses where an axon terminal makes contact with the
target cell is by release of molecules called neurotransmitters that bind to receptors on the target cell
and which may change its behavior. Neurotransmitter is then removed from the synapse. So it's reset to
transmit more information. And I think of this part as similar to the bullet leaving the gun, to hit the
target. The input information that was converted into the size and the duration of graded potentials is
then converted into the temporal pattern of firing of action potentials down the axon. And this
information is then converted to the amount and the temporal pattern of neurotransmitter release at
the synapse.

These steps are how neurons transmit information, often over long distances. This is the general way
that neurons usually function. But there are multiple functional types of neurons. So let's take a look at
some of those. Here I've drawn a few different neurons, with their somas in red, their axons in green,
and their dendrites in blue. And I've drawn a line here to separate between the central nervous system
on this side-- so I'll just write CNS for short-- and the peripheral nervous system on this side-- so I'll just
write PNS for short. And there's some different ways we can categorize functional types of neurons. The
first way is the direction of information flow between the CNS and the PNS.

If a neuron like this pseudounipolar neuron right here brings information from the periphery in toward
the central nervous system, we call that an afferent neuron. Afferent, meaning it's bringing information
into the central nervous system. We can also call this type of neuron a sensory neuron because the
information it's bringing into the central nervous system involves information about a stimulus. And a
stimulus is anything that can be sensed in the internal or external environment, which is to say anything
inside the body or anything outside the body. These neurons are carrying information away from the
central nervous system out into the periphery. So instead of calling them afferent neurons, we call them
efferent neurons. And there are two main kinds of efferent neurons. The first we call motor neurons.
Motor, which means movement.

These are efferent neurons that control skeletal muscle, the main type of muscle that's attached to our
skeleton, that moves us around. These motor neurons are also called somatomotor neurons or neurons
of the somatic nervous system. The other type of the efferent neurons are called autonomic neurons.
And these neurons control smooth muscle, like the muscle around our blood vessels; cardiac muscle, the
muscle of our heart; and gland cells, the cells of our glands that secrete hormones into the bloodstream.
These autonomic neurons are also called visceromotor neurons or neurons of the autonomic nervous
system.

Most neurons of the central nervous system aren't any of these types of neurons, however. They're like
this neuron, in that they connect other neurons together. So these are called interneurons, neurons
between neurons. And there are many interneurons in the central nervous system, forming very
complex pathways for information to travel. So that while an individual neuron is processing and
transmitting information, these complex networks of neurons in the central nervous system are doing
even more complex processing and transmitting of information.

If there's multiple stimulation points on various dendrites, it gets added up and if it meets some
threshold level, it's going to create this action potential or signal that travels across the axon and maybe
stimulates other neurons or muscles because these terminal points of the axons might be connected to
dendrites of other neurons or to muscle cells or who knows what. But what I want to do in this video is
kind of lay the building blocks for exactly what this signal is or how does a neuron actually transmit this
information across the axon-- or really, how does it go from the dendrite all the way to the axon? Before
I actually even talk about that, we need to kind of lay the ground rules-- or a ground understanding of
the actual voltage potential across the membrane of a neuron.

And, actually, all cells have some voltage potential difference, but it's especially relevant when we talk
about a neuron and its ability to send signals. Let's zoom in on a neuron's cell. I could zoom in on any
point on this cell that's not covered by a myelin sheath. I'm going to zoom in on its membrane. So let's
say that this is the membrane of the neuron, just like that. That's the membrane. This is outside the
neuron or the cell. And then this is inside the neuron or the cell.

Now, you have sodium and potassium ions floating around. I'm going to draw sodium like this. Sodium's
going to be a circle. So that's sodium and their positively charged ions have a plus one charge and then
potassium, I'll draw them as little triangles. So let's say that's potassium-- symbol for potassium is K. It's
also positively charged. And you have them just lying around. Let's say we start off both inside and
outside of the cell. They're all positively charged. Sodium inside, some sodium outside. Now it turns out
that cells have more positive charge outside of their membranes than inside of their membranes. So
there's actually a potential difference that if the membrane wasn't there, negative charges would want
to escape or positive charges or positive ions would want to get in. The outside ends up being more
positive, and we're going to talk about why. So this is an electrical potential gradient, right? If this is less
positive than that-- if I have a positive charge here, it's going to want to go to the less positive side. It's
going to want to go away from the other positive charges. It's repelled by the other positive charges.

Likewise, if I had a negative charge here, it'd want to go the other side-- or a positive charge, I guess,
would be happier being here than over here. But the question is, how does that happen? Because left to
their own devices, the charges would disperse so you wouldn't have this potential gradient. Somehow
we have to put energy into the system in order to produce this state where we have more positive on
the charge of the outside than we do on the inside. And that's done by sodium potassium pumps. I'm
going to draw then a certain way. This is obviously not how the protein actually looks, but it'll give you a
sense of how it actually pumps things out. I'll draw that side of the protein. Maybe it looks like this and
you'll have a sense of why I drew it like this. So that side of the protein or the enzyme-- and then the
other side, I'll draw it like this. It looks something like this, and of course the real protein doesn't look
like this. You've seen me show you what proteins really look like. They look like big clusters of things,
hugely complex.

Different parts of the proteins can bond to different things and when things bond to proteins, they
change shape. But I'm doing a very simple diagram here and what I want to show you is, this is our
sodium potassium pump in its inactivated state. And what happens in this situation is that we have
these nice places where our sodium can bind to. So in this situation, sodium can bind to these locations
on our enzyme or on our protein. And if we just had the sodiums bind and we didn't have any energy
going into the system, nothing would happen. It would just stay in this situation. The actual protein
might look like something crazy. The actual protein might be this big cloud of protein and then your
sodiums bond there, there, and there. Maybe it's inside the protein somehow, but still, nothing's going
to happen just when the sodium bonds on this side of the protein. In order for it to do anything, in order
for it to pump anything out, it uses the energy from ATP.

So we had all those videos on respiration and I told you that ATP was the currency of energy in the cell--
well, this is something useful for ATP to do. ATP-- that's adenosine triphosphate-- it might go to some
other part of our enzyme, but in this diagram maybe it goes to this part of the enzyme. And this enzyme,
it's a type of ATPase. When I say ATPase, it breaks off a phosphate from the ATP-- and that's just by
virtue of its shape. It's able to plunk it off. When it plunks off the phosphate, it changes shape. So step
one, we have sodium ions-- and actually, let's keep count of them. We have three sodium-- these are
the actual ratios-- three sodium ions from inside the cell or the neuron. They bond to pump, which is
really a protein that crosses our membrane.

Now, step two, we have also ATP. ATP gets broken into ADP plus phosphate on the actual protein and
that changes the shape. So that also provides energy to change pump's shape. Now this is when the
pump was before. Now after, our pump might look something like this. Let me clear out some space
right here. I'll draw the after pump right there. And so this is before. After the phosphate gets split off of
the ATP, it might look something like this. Instead of being in that configuration, it opens in the other
direction. So now it might look something like this. And of course it's carrying these phosphate groups.
They have a positive charge. It's open like this. This side now looks like this. So now the phosphates are
released to the outside. So they've been pumped to the outside.

Remember, this is required energy because it's going against the natural gradient. You're taking positive
charge and you're pushing them to an environment that is even more positive and you're also taking it
to an environment where there's already a lot of sodium, and you're putting more sodium there. So
you're going against the charge gradient and you're going against the sodium gradient. But now-- I guess
we call it step three-- the sodium gets released outside the cell. And when this changes shape, it's not so
good at bonding with the sodium anymore. So maybe these can become a little bit different too, so that
the sodium can't even bond in this configuration now that the protein has changed shape due to the
ATP. So step three, the three Na plusses, sodium ions-- are released outside.

Now once it's in this configuration, we have all these positive ions out here. These positive ions want to
get really as far away from each other as possible. They'd actually probably be attracted to the cell itself
because the cell is less positive on the inside. So these positive ions-- and in particular, the potassium--
can bond this side of the protein when it's in this-- I guess we could call it this activated configuration. So
now, I guess we could call it step four. We have two potasium ions bond to-- I guess we could call it the
activated pump-- or changed pump. Or maybe we could say it's in its open form. So they come here and
when they bond, it re-changes the shape of this protein back to this shape, back to that open shape.
Now when it goes back to the open shape, these guys aren't here anymore, but we have these two guys
sitting here and in this shape right here, all of a sudden these divots-- maybe they're not divots.
They're actually things in this big cluster of protein. They're not as good at staying bonded or holding
onto these potasiums so these potasiums get released into the cell. So step five, the pump-- this
changes shape of pump. So pump changes shape to original. And then once we're in the original, those
two sodium ions released inside the cell. We're going to see in the next few videos why it's useful to
have those sodium ions on the inside. You might say, well, why don't we just keep pumping things on
the outside in order to have a potential difference? But we'll see these sodium ions are actually also very
useful. So what's the net effect that's going on? We end up with a lot more sodium ions on the outside
and we end up with more potassium ions on the inside, but I told you that the inside is less positive than
the outside. But these are both positive. I don't care if I have more potassium or sodium, but if you paid
attention to the ratios I talked about, every time we use an ATP, we're pumping out three sodiums and
we're only pumping in two potassiums, right?

We pumped out three sodiums and two potassiums. Each of them have a plus-1 charge, but every time
we do this, we're adding a net-1 charge to the outside, right? 3 on the outside, 2 to the inside. We have
a net-1 charge-- we have a plus-1 to the outside. So we're making the outside more positive, especially
relative to the inside. And this is what creates that potential difference. If you actually took a voltmeter--
a voltmeter measures electrical potential difference-- and you took the voltage difference between that
point and this point-- or more specifically, between this point and that point, if you were to subtract the
voltage here from the voltage there, you will get -70 millivolts, which is generally considered the resting
voltage difference, the potential difference across the membrane of a neuron when it's in its resting
state.

So in this video, I kind of laid out the foundation of why and how a cell using ATP, using energy, is able to
maintain a potential difference across its membrane where the outside is slightly more positive than the
inside. So we actually have a negative potential difference if we're comparing the inside to the outside.
Positive charge would want to move in if they were allowed to, and negative charge would want to
move out if it was allowed to. Now there might be one last question. You might say, well, if we just kept
adding charge out here, our voltage difference would get really negative. This would be much more
negative than the outside. Why does it stabilize at -70? To answer that question-- these are going to
come into play in a lot more detail in future videos-- you also have channels, which are really protein
structures that in their open position will allow sodium to go through them.

And there are also channels that are in their open position, would allow potassium to go through them.
I'm drawing it in their closed position. And we're going to talk in the next video about what happens
when they open. But in their closed position, they're still a little bit leaky. And if, say, the concentration
of potassium becomes too high down here-- and too high meaning when they start to reach this
threshold of -70 millivolts-- or even better, when the sodium gets too high out there, a few of them will
start to leak down. When the concentration gets really high and this is really positive just because of the
electrical potential, some of them will just be shoved through.

So it'll keep us right around -70 millivolts. And if we go below, maybe some of the potassium gets leaked
through the other way. So even though when these are shut-- if it becomes too ridiculous-- if it goes to
-80 millivolts or -90 millivolts, all of a sudden, there'd be a huge incentive for some of this stuff to leak
through their respective channels. So that's what allows us to stay at that stable voltage potential. In the
next video, we're going to see what happens to this voltage potential when the neuron is actually
stimulated.

********

Two corrections I want to make to the video on the sodium potassium pump. One very minor one-- and I
don't think it would trip too many of you guys up, but near the end of the video, as we learned, we have
potassium getting pumped into the cell by the sodium potassium pump. Let me draw the membrane. It'll
actually be useful in the more significant correction I'd like to make. So let me draw a cross section of a
cell membrane. And let me draw the sodium potassium pump right here. We saw it pumps out three
sodiums for every two potassiums that it pumps in. It definitely doesn't look like that, but it gives the
idea. And we're pumping potassium ions in-- so K plus-- and we're pumping sodium ions out-- and that's
what the whole point of that video was. When this thing changes shape with ATP, it pumps the sodium
ions out. Now the minor correction I want to make-- and I don't think it would have tripped you up too
much-- is near the end of that video, I drew the potassium ions-- and I wrote a K plus, but a few times
near the end of the video, I referred to them as sodium ions-- and I don't want that to confuse you at all.
It is potassium ions that are getting pumped in. Two potassium ions get pumped in for every three
sodium ions that get pumped out. So I don't want-- even thought I drew a K plus, sometimes I said
sodium by accident. Don't want that to confuse you. That is the minor error. The more significant error
is that I said that the main reason that we had this potential difference-- why it is more positive on the
outside than the inside-- so this is less positive. I said that the main reason was because of this ratio.
We're pumping out three sodium ions for every two potassium ions that we pump in. And I just got a
very nice letter from a professor of physiology, Steven Baylor at University of Pennsylvania, and he
wrote a very interesting email and it corrects me. And it's a very interesting thing to think about in
general. So here's what he wrote and let's think about what he's saying. He says: Here at Penn Medical
School, we have a nice teaching program that stimulates the ion fluxes across a generic cell, --So the ion
flux is just the movement of the ions across the membrane-- including that due to the sodium potassium
pump and that which arises from the resting permeabilities of the membrane. So the resting
permeabilities is how easy it is for these ions to go through the membrane. And we'll talk more about
that in a second. And the resting permeabilities of the membrane to sodium, potassium, chloride, et
cetera. One option our program gives students is to change the pump stoichiometry from three to two.
So when he's talking about pump stoichiometry from three to two, he's just talking about they're
changing the ratios. So they change it from 3:2 to 2:2. So what that means is, they have a simulation
program that says, well, what if the sodium potassium pump, instead of pumping three sodiums out for
every two potassium it pumps in, what if it was even? What if it was two sodiums and two potassiums?
And based on my explanation of why we have this potential difference, that should not lead to a
potential difference if the main reason was the stoichiometry-- the ratio of sodium being pumped to the
potassium being pumped in. But he goes on to say: They could change it to 2:2 in the simulation. As a
result of this maneuver, the membrane potential changes from its normal value of about -80 millivolts--
and they measure that. They take the voltage here minus the voltage there so that you get a negative
number. This is more positive. It's a larger number. So it changes from -80 millivolts to about -78
millivolts. So what he's saying is, if you change this from three and two-- three sodiums for every two
potassiums that get pumped in-- if you change that to 2:2, it actually doesn't change the potential that
much. You still have a more positive environment outside than you have inside. So that leads to the
question-- then why do we have the potential if the stoichiometry of this ratio is not the main cause? So
it says, it changes a little bit. The potential difference becomes a little bit less. The cell swells a few
percentage and then everything stabilizes. So then he goes on to write: So while it is true that the
normal stoichiometry of the pump does have a slight negative influence on the membrane potential--
that's just the membrane potential, the voltage across the membrane-- the imbalance in the pump
stoichiometry is not the main reason for the large negative membrane potential of the cell. Rather, the
main-- let me underline this-- the main reason is the concentration gradients established by the pump in
combination with the fact that the resting cell membrane is highly permeable to potassium and only
slightly permeable to sodium. So we said in the last video-- or the first video on the sodium potassium
pump-- we said there were channels that the sodium could go through and there's also channels that
the potassium could go through. And now what he's saying is that the main cause of the potential
difference isn't this ratio, it's the fact that the membrane is highly permeable to potassium. So this is
very permeable. Potassium can get out if it wants to, much easier than it is for sodium to get in. So what
that happens-- even if this was a 2:2 ratio-- it's actually a 3:2, but even if this was a 2:2 ratio, even
though this environment is more positive, you're just more likely to have to potassium ions down here
bump in just the right way to get across and get to the other side, go against its chemical gradient, right,
because you have a higher concentration of potassium here than over here. So you're more likely to
have a potassium bump in just the right way to get through this channel and get out-- than you are to
have a sodium be able to go the opposite direction. And that's what makes this environment. So you
have more potassium coming outside because of this permeability than sodium coming inside-- and
that's the main cause of the potential difference between the outside and the inside. And so thank you,
Steven Baylor, for that correction. Very interesting.

**************

We've already seen that when a neuron is in its resting state there's a voltage difference across the
membrane. And so in these diagrams right over here, this right over here is the membrane. This right
over here is the inside of the neuron, and this right over here is the outside. That's the outside and of
course this is the outside. This is the outside as well. So if you had a voltmeter measuring the potential
difference across the membrane, so if you took this voltage minus this voltage right over here, the
voltage between this and that, you would get negative-- let's say for the sake of argument, let's say it
would measure, it would average about negative 70 millivolts.

So this is in millivolts, negative 70. And I'll do it actually for both of these graphs. We're going to use
both of these to describe slightly different, or actually quite different, scenarios. And you could have
another voltmeter out here in yellow, and that's a little further out, but that's also going to register
negative 70 millivolts. Now let's make something interesting happen. Let's say that, for some reason,
let's say that the membrane becomes permeable to sodium. So sodium just starts flooding through. It's
going to flood through for two reasons. One, it is a positive ion. It's more positive on the outside than
the inside, so positive charge will want to flood in.
And the other reason why it'll want to flood in is because there's a higher concentration of sodium on
the outside than on the inside. So it'll just go down its concentration gradient. And the reason why we
have a higher concentration gradient on the sodium on the outside than the inside, we've already seen,
is because of the sodium potassium pump. But anyway, so you're going to have this increase. You're
going to really have this spike in positive charge flowing. And then what's going to be the dynamic then
inside the neuron? Well, if you have all this positive charge right over here the other positive charge in
the neuron is going to want to get away from it.

And this is not just in the rightward direction. It's really going to be in all directions. In all directions the
positive charge, they're going to want to get away from each other. So this one's going to move that
way, and then that's going to make that one want to move that way, which is going to make that one
want to move that way. So if we let some time pass, what's the voltage going to look like on this blue
voltmeter? Well after some time, because more and more positive charges are trying to get away from
these other ones right over here as the concentration of these positive charges spread out, you're going
to see the voltage start to increase.

And then as they fully get spread out then it might return to something of an equilibrium. And then if we
go a little bit further down the neuron a little more time will pass before you see a voltage increase, but
because this thing is just getting spread out across more and more distance, the effect is going to be
more limited. You're not going to see as much of a bump in the voltage over here than you saw over
here. And this type of spread of, I guess you could say a signal, is called electrotonic spread. Let me write
that down. Or this is the spread of an electrotonic potential. So there's a couple of characteristics here.
One, it's passive. This part that we drew right here, this isn't the electrotonic spread. The electrotonic
spread is what happens after that. Once you have this high concentration here, the fact that a few
moments later you're going to have a higher concentration of positive charge here, and a few moments
later a higher positive concentration here.

This is a passive phenomenon. So this thing right over here, it is passive. And it also dissipates. The signal
gets weaker and weaker the further and further you get out because this stuff just gets further and
further spread out. So it's passive and it dissipates. Now let's play out this scenario again, but let's also
throw in some voltage-gated ion channels right over here. So let's say this right over here that I'm
drawing, let's say this is a voltage-gated sodium channel. Let's say it opens at negative 55 millivolts. So
that would be right around there. So that is when it opens at negative 55 millivolts. Let me draw that
threshold there. And let's say it closes at positive 40 millivolts, right over there. I'm just trying to show
the threshold.

And let's say we also have a potassium channel too, right over here. So this is a potassium channel, the
infamous leaky potassium channels, which are the true reason why we have this voltage difference
across the membrane. But this potassium channel, let's say it opens when this one closes. So it opens,
just for the sake of argument, these aren't going to be the exact numbers but to give you the idea, at
positive 40 millivolts. And let's say it closes at negative 80 millivolts. So that one opens up here, and then
it closes down here. Now what is going to happen? Well just like we saw before-- Let's let our positive
charge flood in here at the left side of this neuron, I guess we could say, and then because of
electrotonic spread, a little bit later you're going to have the potential across the membrane at this point
is going to start to become less negative. The potential difference is going to become less negative, just
like we saw right over here. So it's going to become less negative.

But it's not just going to be just a little bump and then go back down, because what happens right when
the potential hits negative 55 millivolts? Well then it's going to trigger the opening of this sodium
channel. So the sodium channel is going to open because the voltage got high enough, and so you're
going to have sodium flood in again. So what's that going to do? Well that's going to spike up the
voltage. So it's going to look something like that. It's going to keep flowing in, keep flowing in. The
voltage is going to get more and more positive.

Because remember, this is going to be flowing in for two reasons. One, there's just more charge. It's
more positive outside than the inside so it's going to go across a voltage gradient, or go down the
voltage gradient, or the electro potential gradient, but also there's a higher concentration of sodium out
here than there is in here because of the sodium potassium pump, and so it'll also want to go down its
concentration gradient. So it's just going to keep flowing in even past the point at which you have no
voltage gradient, but because of the concentration gradient it's going to keep going. But then, as you get
to positive 40 millivolts, this channel is going to close. So that's going to stop flooding in.

And you also have the potassium channel opening. And the potassium channel, now you're more
positive on the inside than the outside, at least locally right over here. And so now you're going to have
this positively-charged potassium ions want to get out, want to get out from this positive environment.
And so the voltage is going to get more and more negative, and it's going to go beyond neutral because
potassium is going to want to go down, not just its voltage gradient, it's going to do that while it's
positive on the inside and negative on the outside, or more positive on the inside than it is on the
outside, but it'll also want to go down its concentration gradient. There's a higher concentration of
potassium on the inside than on the outside because of the sodium potassium pump.

So the potassium will just keep going out, and out, and out, and out, and then at negative 80 millivolts
the potassium channel closes, and then we can get back to our equilibrium state. Now why is this
interesting? Well we had the electrotonic spread up to this point. But the signal would just keep
dissipating and keep dissipating, and if you get far enough it would be very hard to notice that signal.
And so what this essentially just did is it just boosted the signal again. It just boosted the signal, and
now, a few moments later, if you were to measure the potential difference-- because these things are
trying to get away from each other again, once again you have electrotonic spread-- if you were to
measure the potential difference across the membrane where this yellow voltmeter is, then you're going
to have-- So where that yellow one is, before it had just a little dissipated bump here, but now it's going
to have quite a nice bump.

And if you actually had another voltage-gated channel right over here, then that would boost it again.
And so this kind of very active boosting of the voltage, this is called an action potential. You could view
this as the boosting of the signal. The signal is spreading, electrotonic spread, then you trigger a channel,
a voltage-gated channel, then that boosts the signal again. And as we'll see, the neuron uses a
combination, just the way we described it here, in order to spread a signal, in order for it to have the
signal spread, in order to obviously to spread passively, but then to boost it so that the signal can cover
over long distances.

So we've already talked about the dendrites as being where the neuron can be stimulated from multiple
inputs. If we're in the brain, these dendrites might be near the terminal ends of axons of other neurons.
If we're some type of sensory cell, these dendrites could be stimulated by some type of sensory input.
But let's just say, for the sake of argument, they are stimulated in some way. And because they're
stimulated in some way, it allows positive ions to flood into the neuron from the outside. As we know,
there's a potential difference. It's more negative inside of the neuron than outside of the neuron. And so
if a channel gets opened up because of some stimulus, that would allow positive ions to flow in. And the
primary positive ions we've been talking about are the sodium ions. Maybe this is some type of sodium
gate that gets opened up because of this stimulus.

So when that happens, you will have electrotonic spread. You will have an electrotonic potential being
spread. So let's say that we had a voltmeter right here on the axon hillock. It's kind of the hill that leads
to the axon right over here. So what you might see happening after some amount of time-- so let me
draw. So let's say this is our voltage in millivolts across the membrane-- our voltage difference, I should
say. This is the passage of time. Let's say the stimulus happens at time 0. But right at time 0, we haven't
really noticed it with our voltmeter. Our voltage right across the membrane right over there is at that
equilibrium, negative 70 millivolts. But after some small amount of time, this electrotonic potential has
gotten to this point, because all of these positive charges are trying to get away from each other.

It's gotten to that point. And you might see a bump in the voltage-- in the voltage difference, I guess I
should say. This thing might go up. So it might look something like that. Now, that by itself might not
be-- we might have gotten the voltage difference low enough, I guess we could say. Or we might not
have gotten the voltage inside of the cell positive enough in order to trigger the voltage-gated ion
channels. And so maybe nothing happens. Maybe this right over here, this is negative 55 millivolts. And
so that's what you have to get the voltage up to, the voltage difference up to, in order to trigger the ion
channels right over there. So those are the sodium channels to get positive charge in. Here's the
potassium channels to get the positive charge out.

The axon hillock has a ton of these, because these are really there. Once they get triggered, they can
trigger an impulse that can then go down the entire axon, and maybe stimulate other things, maybe in
the brain or whatever else this neuron might be connected to. So maybe that stimulus by itself didn't
trigger it. But let's say that there's another stimulus that happens right at the same time, or around the
same time. And that happens. And on its own, that might have caused a similar type of bump right over
here. But when you add the two together and they're happening at the same time, their combined
bumps are enough to trigger an action potential in the hillock, or a series of action potentials in the
hillock. And so then, you really have, essentially, fired the neuron.

So now all sorts of positive charge gets flushed into the neuron. And then purely through electrotonic
spread, you will have this electrotonic potential spread down the axon. Now, this is the interesting part,
because we can think a little bit about, what is the best way for an axon to be designed? In general, if
you're trying to transfer a current, the ideal thing to do is, the thing that you're transferring the current
down should conduct really well. Or you could say it has low resistance. But you want it to be
surrounded by an insulator. You want it to be surrounded. So if this was a cross section, you want it to
be surrounded by an insulator that has high resistance. And the reason is because you don't want the
potential to leak across your membrane-- high resistance right over here. If you didn't have something
high resistance around it, your current would actually go slower.

This is true if you're just dealing with electronics. If you just had a bunch of copper wires on one side,
and you had some copper wires that were surrounded by a really good insulator, a really good resistor--
for example, plastic or rubber of some kind. The current is actually going to have less energy loss. It's
going to travel faster when it's surrounded by an insulator. So you might say, OK, well gee. The best
thing to do would be to surround this entire axon with a good insulator. And for the most part, that is
true. It is surrounded by a good insulator. That is what the myelin sheath is. So let's say we want to
surround this whole thing with just one big grouping of Schwann's cells, so one big myelin sheath--
which is a good insulator. It does not conduct current well. So this right over here is just one big myelin
sheath right over here. Now, what's the problem with this?

Well, if this axon is really long-- and let's say, you know, you're a dinosaur or something. And you're
trying to go up your neck, and your neck is 20 feet long. Or even a human being, we're a reasonable size.
And you're going several feet, or even whatever, you want to go a reasonable distance purely with
electrotonic spread, your signal, remember, it dissipates. Your signal is going to be really weak right over
here. You're going to have a weak signal on the other end. It might not be even strong enough to make
anything interesting happen at these terminals, which wouldn't be strong enough to trigger, maybe,
other neurons, or whatever else might need to happen at this other end. So then you say, OK, well then
why don't we try to boost the signal? Well, how would you boost the signal?

You say, OK. I like having this myelin sheath. But why don't we put gaps in the myelin sheath every so
often? And then those gaps would allow the membrane to interface with the outside. And in those
areas, we could put some voltage-gated channels that can release action potentials, in order to
essentially boost the signal. And that's is exactly what the anatomy of a typical neuron is like. So instead
of just one big insulating sheath like this, it would-- let me make some gaps here. Whoops, I'm going to
do that in black. So actually, let me just draw it like this. Let me just erase this. So clear, and let me clear
this. That's good enough. And so what we could do is we could put gaps in it right over here where the
axon, the axonal membrane itself can interface with its surroundings. And of course, we know we call
those gaps the nodes of Ranvier, or Ran-Veer. I'm not really sure how to pronounce it.

So let me put those gaps in here. So you put those gaps in here, so these are the myelin sheath. And this
right over here is a node of Ranvier. These are nodes of Ran-Veer, or Ranvier. And right in those little
nodes, right in those nodes, right where the myelin sheath isn't, we can put these voltage-gated
channels to essentially boost the signal. If the signal had to go electrotonically all the way over here, it'd
be very weak. It's going to dissipate as it goes down, but it could be just strong enough right at this point
in order to trigger these voltage-gated channels, in order to essentially boost the signal again, in order to
trigger an action potential, boost the signal. And now the signal is boosted, it'll dissipate, dissipate,
dissipate, boost. And it'll boost right over here again. And then it'll dissipate, dissipate, dissipate, and
boost. Dissipate, dissipate, boost. And so by having this combination, you want the myelin sheath. You
want the insulator in order to keep the transmission of the current to fast, in order to have minimal
energy loss. But you do need these areas where the myelin sheath isn't in order to boost the signal, in
order for the action potentials to get triggered, and so your signal can keep being-- well, I guess keep
being amplified, if we wanted to talk in kind of electrical engineering speak.

And this type of conduction, where the signal just keeps boosting, and if you were just to superficially
observe it, it looks like the signal is almost jumping. It gets triggered here, then it gets triggered, here
then it gets triggered here, then it gets triggered here, then it gets triggered here. This is called saltatory
conduction. It comes from the Latin word saltare-- once again, I don't know how to pronounce. My Latin
isn't too good. But it comes from the Latin word saltare, which means to jump around or to hop around.
And that's because it looks like the signal is hopping around.

But that's not exactly what's happening. The signal is traveling passively through. It gets triggered here
in the axon hillock. Then it travels passively through electrotonic spread. And then it gets boosted. And
you have the myelin sheath around it to make sure it goes as fast as possible, and you get very little loss
of signal. And then it gets boosted at the nodes of Ranvier, because it triggers these voltage-gated
channels again. That triggers an action potential. And then your signal gets boosted, and then it
dissipates-- boosted, dissipates, boosted, dissipates, boosted, dissipates. Maybe it could even get
boosted again. And then it can trigger whatever else it has to trigger.

Synapses are where neurons contact and communicate with their target cells, and the word "synapse"
comes from Greek words meaning "to clasp together." So let me start by showing where synapses
happen, so first I'll draw the soma of a neuron in red, and a few dendrites, these branching processes of
neurons in blue, one dendrite and here's another dendrite. And then I'll draw the axon of the neuron in
green. It's this long unbranched process, until it reaches the end, and then it branches into multiple
terminals, and I'll just draw a few here, but it can have many, many terminals.

And then let me just draw some target shapes to represent the types of target cells that a neuron may
contact with the synapse. And these cells may be another neuron, they might be a muscle cell, or they
may be a gland cell, and some neurons even have axon terminals that end on blood vessels to secrete
substances into the bloodstream, called hormones. So synapses are these spots, where the axon
terminals of a neuron are contacting their target cell, and there are a couple of types of synapses, one of
which has a gap like I've drawn here, although it's actually a much smaller gap than I've drawn, and the
other one doesn't have a gap. They are physically connected.

The type of synapse that has a gap is called a chemical synapse, because it releases molecules, or
chemicals, at the synapse that cross from the axon terminal to the membrane of the target cell. The
other type of synapse is called an electrical synapse. And with this type of synapse, the cells are actually
physically connected, so that the axon terminal physically connects with the membrane of the target
cell, and there are special channels called "gap junctions" that actually let the inside of the neuron
communicate with the inside of the target cell. The cytoplasm of the two are really connected, and ions
can flow directly from the neuron into the target cell. In this set of videos, I'm just gonna talk about the
chemical synapses, where there is a gap, because they are far and away more common than electrical
synapses, which are fairly rare, at least in humans.

Now a typical human neuron can have a massive number of connections through synapses. It can
connect thousands of different target cells through its axon terminals, and the typical neuron receives
information through thousands of synapses. Most of those synapses come in to the dendrites, so that
the axon of another neuron is contacting and communicating with the dendrite of this neuron, and
there could be many, many synapses on a dendrite, and part of the reason it's branched, is just so that it
can have more surface area, to form more synapses. So that for most neurons, most of the synapses are
actually coming in through their dendrites.

However most neurons also do get a smaller number of synapses coming in to the soma. And there are
even synapses onto the axon, but usually not just anywhere onto the axon, it's usually onto the axon
terminal, so that this axon comes in, and its axon terminal is synapsing on the axon terminal of this
neuron. And it could be the same with this axon terminal, it could have synapses, and this axon terminal
right here. And so try to imagine thousands of synapses just literally covering this whole neuron, and
that it in turn is connecting with thousands of target cells through synapses. And you can just imagine
how complex the information is that's flowing into and out of the neuron from other parts of the
nervous system. But now let's zoom in, and let's look at the structure of an individual synapse, like for
instance this synapse right here. Let me start by drawing a big axon terminal, so I'll just blow up that
axon terminal and make it really big here in green, and then I'll just draw a target type of shape to
represent the target cell, which again could be another neuron, could be a muscle cell, or it could be a
gland cell.

And then in the central nervous system, covering most of the synapses are the end feet of astrocytes.
Now let me just draw that in purple, and I'll actually just label that, let me just write "astrocyte," and this
would be one of the end feet of the astrocyte that, in the central nervous system are just plastered all
over synapses. So for a chemical synapse like this, there is a gap here, between the membrane of the
axon terminal of the neuron, and the membrane of the target cell. And the gap is actually much smaller
than this, but I just needed a little room to draw. It's a very, very small gap, but the cells are not actually
physically touching each other. There is a gap. And we call this gap the synaptic cleft. Let me just write
that out - synaptic cleft.

And that's the space between the neuron and the target cell, and then we have names for this piece of
membrane over here, and this piece of membrane. This membrane facing the synaptic cleft, on the axon
terminal of the neuron, we call the presynaptic membrane, presynaptic membrane is right here,
because it's before the synaptic cleft. And then this piece of membrane on the target cell facing the
synaptic cleft is the postsynaptic membrane, postsynaptic membrane, and that's right over here. And so
it's presynaptic because it's before the synaptic cleft, and it's postsynaptic because it's after the synaptic
cleft. Just on the inside of the presynaptic membrane are vesicles, which are little membrane-enclosed
bubbles inside the cytoplasm of the neuron, and these are called synaptic vesicles. Synaptic vesicles -
that's each of these bubble-like structures just inside the presynaptic membrane of the neuron. And
these synaptic vesicles are full of molecules called neurotransmitter.

Let's draw a couple of dots in here to represent these molecules, and they are called collectively
neurotransmitter, because they transmit information from the neuron to the target cells, and all of
these molecules are collectively called neurotransmitters. And there are different types of
neurotransmitters, that we'll get into on other videos. On the postsynaptic membrane are receptors that
are specific for the neurotransmitter in the synaptic vesicles. The neurotransmitter will fit like a key in a
lock to these neurotransmitter receptors on the postsynaptic membrane. And in the next video we'll talk
about how the neurotransmitter and the synaptic vesicles is released from the presynaptic membrane to
cross the synaptic cleft, and bind to its receptors on the postsynaptic membrane.

I think we have a decent idea of how a signal is transmitted along the neuron. We saw that a couple of
dendrites, maybe that one and that one and that one, might get excited or triggered. And when we say
it gets triggered, we're saying that some type of channel gets opened. That's probably the trigger. That
channel allows ions to be released into the cell-- or actually, there are situations where ions can be
released out of the cell. It would be inhibitory, but let's take the case where ions are released into the
cells in an electrotonic fashion. It changes the charge or the voltage gradient across the membrane and
if the combined effects of the change in the voltage gradient is just enough at the axon hillock to meet
that threshold, then the sodium channels over here will open up, sodium floods in, and then we have
the situation where the voltage becomes very positive.

Potassium channels open up to change things again, but by the time we went very positive, then that
eletrotonically affects the next sodium pump. But then we have the situation where that will allow
sodium ions to flood in and then the signal keeps getting transmitted. Now the next natural question is,
what happens at the neuron to neuron junctions? We said that this dendrite gets triggered or gets
excited. In most cases, it's getting triggered or excited by another neuron. It could be something else.
And over here, when this axon fires, it should be exciting either another cell. It could be a muscle cell
or-- in probably most cases of the human body-- it's exciting another neuron. And so how does it do
that? So this is the terminal end of the axon. There could be the dendrite of another neuron right here.
This is another neuron with its own axon, its own cell. This would trigger the dendrite right there.

So the question is, how does that happen? How does the signal go from one neuron's axon to the next
neuron's dendrite? It actually always doesn't have to go from axon to dendrite, but that's the most
typical. You can actually go from axon to axon, dendrite to dendrite, axon to soma-- but let's just focus
on axon to dendrite because that's the most traditional way that neurons transmit information from one
to the other. So let's zoom in. Let's zoom in right here. This little box right there, let's zoom at the base,
the terminal end of this axon and let's zoom in on this whole area. Then we'll also zoom in-- we're also
going to get the dendrite of this next neuron-- and I'm going to rotate it. Actually, I don't even have to
rotate it. So to do that, let me draw the terminal end. So let's say the terminal end looks something like
this. I'm zoomed in big time. This is the terminal end of the neuron. This is inside the neuron and then
the next dendrite-- let me draw it right here. So we've really zoomed in.
So this is the dendrite of the next neuron. This is inside the first neuron. So we have this action potential
that keeps traveling along. Eventually for maybe right over here-- I don't know if you can zoom in--
which would be over here, the action potential makes the electrical potential or the voltage potential
across this membrane just positive enough to trigger this sodium channel. So actually, maybe I'm really
close. This channel is this one right here. So then it allows a flood of sodium to enter the cell. And then
the the whole thing happens. You have potassium that can then take it out, but by the time this comes
in, this positive charge, it can trigger another channel and it could trigger another sodium channel if
there's other sodium channels further down, but near the end of the axon there are actually calcium
channels. I'll do that in pink. So this is a calcium channel that is traditionally closed. So this is a calcium
ion channel. Calcium has a plus 2 charge. It tends to be closed, but it's also voltage gated.

When the voltage gets high enough, it's very similar to a sodium voltage gated channel is that if it
becomes positive enough near the gate, it will open up and when it opens up, it allows calcium ions to
flood into the cell. So the calcium ions, their plus 2 charge, to flood into the cells. Now you're saying, hey
Sal, why are calcium ions flooding into the cells? These have positive charge. I just thought you said that
the cell is becoming positive because of all the sodium flowing in. Why would this calcium want to flow
in? And the reason why it wants to flow in is because the cell also-- just like it pumps out sodium and
pumps in potassium, the cell also has calcium ion pumps and the mechanism is nearly identical to what I
showed you on the sodium potassium pump, but it just deals with calcium. So you literally have these
proteins that are sitting across the membrane. This is a phospobilipid layer membrane.

Maybe I'll draw two layers here just so you realize it's a bi-layer membrane. Let me draw it like that.
That makes it look a little bit more realistic, although the whole thing is not very realistic. And this is also
going to be a bilipid membrane. You get the idea, but let me just do it to make the point clear. So there
are also these calcium ion pumps that are also subsets of ATPases, which they're just like the sodium
potassium pumps. You give them one ATP and a calcium will bond someplace else and it'll pull apart the
phosphate from the ATP and that'll be enough energy to change the confirmation of this protein and it'll
push the calcium out. Essentially, what was the calcium will bond and then it'll open up so the calcium
can only exit the cell. It's just like the sodium potassium pumps, but it's good to know in the resting
state, you have a high concentration of calcium ions out here and it's all driven by ATP. A much higher
concentration on the outside than you have on the inside and it's driven by those ion pumps.

So once you have this action potential, instead of triggering another sodium gate, it starts triggering
calcium gates and these calcium ions flood into the terminal end of this axon. Now, these calcium ions,
they bond to other proteins. And before I go to those other proteins, we have to keep in mind what's
going on near this junction right here. And I've used the word synapse already-- actually, maybe I
haven't. The place where this axon is meeting with this dendrite, this is the synapse. Or you can kind of
view it as the touching point or the communication point or the connection point. And this neuron right
here, this is called the presynaptic neuron. Let me write that down. It's good to have a little terminology
under our belt. This is the post-synaptic neuron.

And the space between the two neurons, between this axon and this dendrite, this is called the synaptic
cleft. It's a really small space in the terms of-- so what we're going to deal with in this video is a chemical
synapse. In general, when people talk about synapses, they're talking about chemical synapses. There
also are electrical synapses, but I won't go into detail on those. This is kind of the most traditional one
that people talk about. So your synaptic cleft in chemical synapses is about 20 nanometers, which is
really small. If you think about the average width of a cell as about 10 to 100 microns-- this micron is 10
to the minus 6. This is 20 times 10 to the minus 9 meters. So this is a very small distance and it makes
sense because look how big the cells look next to this small distance. So it's a very small distance and
you have-- on the presynaptic neuron near the terminal end, you have these vesicles.

Remember what vesicles were. These are just membrane bound things inside of the cell. So you have
these vesicles. They also have their phospobilipid layers, their little membranes. So you have these
vesicles so these are just-- you can kind of view them as containers. I'll just draw one more just like that.
And they can train these molecules called neurotransmitters and I'll draw the neurotransmitters in
green. So they have these molecules called neurotransmitters in them. You've probably heard the word
before. In fact, a lot of drugs that people use for depression or other things related to our mental state,
they affect neurotransmitters. I won't go into detail there, but they contain these neurotransmitters.

And when the calcium channels-- they're voltage gated-- when it becomes a little more positive, they
open calcium floods in and what the calcium does is, it bonds to these proteins that have docked these
vesciles. So these little vesicles, they're docked to the presynpatic membrane or to this axon terminal
membrane right there. These proteins are actually called SNARE proteins. It's an acronym, but it's also a
good word because they've literally snared the vesicles to this membrane. So that's what these proteins
are. And when these calcium ions flood in, they bond to these proteins, they attach to these proteins,
and they change the confirmation of the proteins just enough that these proteins bring these vesicles
closer to the membrane and also kind of pull apart the two membranes so that the membranes merge.
Let me do a zoom in of that just to make it clear what's going on.

So after they've bonded-- this is kind of before the calcium comes in, bonds to those SNARE proteins,
then the SNARE protein will bring the vesicle ultra-close to the presynaptic membrane. So that's the
vesicle and then the presynaptic membrane will look like this and then you have your SNARE proteins.
And I'm not obviously drawing it exactly how it looks in the cell, but it'll give you the idea of what's going
on. Your SNARE proteins have essentially pulled the things together and have pulled them apart so that
these two membranes merge. And then the main side effect-- the reason why all this is happening-- is it
allows those neurotransmitters to be dumped into the synaptic cleft.

So those neurotransmitters that were inside of our vesicle then get dumped into the synaptic cleft. This
process right here is called exocytosis. It's exiting the cytoplasm, you could say, of the presynaptic
neuron. These neurotransmitters-- and you've probably heard the specific names of many of these--
serotonin, dopamine, epinephrine-- which is also adrenaline, but that's also a hormone, but it also acts
as a neurotransmitter. Norepinephrine, also both a hormone and a neurotransmitter. So these are
words that you've probably heard before. But anyway, these enter into the synaptic cleft and then they
bond on the surface of the membrane of the post-synaptic neuron or this dendrite. Let's say they bond
here, they bond here, and they bond here. So they bond on special proteins on this membrane surface,
but the main effect of that is, that will trigger ion channels. So let's say that this neuron is exciting this
dendrite. So when these neurotransmitters bond on this membrane, maybe sodium channels open up.
So maybe that will cause a sodium channel to open up.

So instead of being voltage gated, it's neurotransmitter gated. So this will cause a sodium channel to
open up and then sodium will flow in and then, just like we said before, if we go to the original one,
that's like this getting excited, it'll become a little bit positive and then if it's enough positive, it'll
electrotonically increase the potential at this point on the axon hillock and then we'll have another
neuron-- in this case, this neuron being stimulated. So that's essentially how it happens. It actually could
be inhibitory. You could imagine if this, instead of triggering a sodium ion channel, if it triggered a
potassium ion channel. If it triggered a potassium ion channel, potassium ion's concentration gradient
will make it want to go outside of the cell.

So positive things are going to leave the cell if it's potassium. Remember, I used triangles for potassium.
And so if positive things leave the cell, then if you go further down the neuron, it'll become less positive
and so it'll be even harder for the action potential to start up because it'll need even more positive
someplace else to make the threshold gradient. I hope I'm not confusing you when I say that. So this
connection, the way I first described it, it's exciting. When this guy gets excited from an action potential,
calcium floods in. It makes these vesicles dump their contents in the synaptic cleft and then that will
make other sodium gates open up and then that will stimulate this neuron, but if it makes potassium
gates open up, then it will inhibit it-- and that's how, frankly, these synapses work. I was about to say
there's millions of synapses, but that'd be incorrect. There's trillions of synapses.

The best estimate of the number of synapses in our cerebral cortex is 100 to 500 trillion synapses just in
the cerebral cortex. The reason why we can have so many is that one neuron can actually form many,
many, many, many synapses. I mean, you can imagine if this original drawing of a cell, you might have a
synapse here, a synapse here, a synapse there. You could have hundreds or thousands of synapses even,
into one neuron or going out of one neuron. This might be a synapse with one neuron, another one,
another one, another one. So you'd have many, many, many, many, many connections. And so synapses
are really what give us the complexity of what probably make us tick in terms of our human mind and all
of that. But anyway, hopefully you found this useful.

Neurotransmitters are molecules that communicate information between neurons and their target cells
and chemical synapses. There may be hundreds of different types of neurotransmitters and they can be
categorized in a number of different ways, but probably the most common as to divide them up by their
molecular structure into amino acids, peptides, monoamines and others. I'm gonna mention a bunch of
chemistry terms next. Don't worry about them if you don't know them but if you are interested there
are many great videos on these topics on the Khan Academy. The first category of neurotransmitters I'm
gonna represent with these three neurotransmitters right here and this category is the amino acids.
Amino acid neurotransmitters. Amino acids.

That's these three right here. Amino acids have an amino group, this guy right here and they have a
carboxylic acid group. This part right here. There are lots of different types of amino acids but just a few
of them function as neurotransmitters in the nervous system. The next category of neurotransmitters
I'm gonna represent with this one right here and these are the peptides. Peptide neurotransmitters and
I'll just have this one representative here. Peptides are actually polymers or chains of amino acids. A
bunch of these amino acids get strung together in these chains, these polymers and we call them
peptides. Peptides are much larger molecules than all the other types of neurotransmitters. Sometimes
people divide up neurotransmitters just into peptides and they lump together all the other
neurotransmitters and call them small molecule neurotransmitters. The neurotransmitters in this row
will represent our next big category which are the monomines.

Monoamine neurotransmitters, monoamines. That's this whole row. I've picked out five representative
neurotransmitters for the monoamines. These are also sometimes called biogenic amines. Either
monoamines or biogenic amines. The monoamines are organic molecules with an amino group here and
here and here, here and here connected to an aromatic group here, here, here, here and here. The
amino group and aromatic group are connected by a two carbon chain, this part here and here and
here, here and here. Some of the monoamines, these three. Draw little stars next to these three, are
also called by a different name and that name, and let me draw a little star. That name is the
catecholamines. Catecholamines. Catecholamines are a subgroup of the monoamines and the
catecholamines have a catachol group which is this part right here which has a benzine, this ring and
two hydroxyl groups. Here's one hydroxyl group and here's another hydroxyl group. This catechol group,
all the catecholamines have this group these three right here.

There are many other types of neurotransmitters that are not amino acids or monoamines or peptides
and this neurotransmitter right here is gonna be the representative for that. I'll just call this category
other. These are the other molecular types of neurotransmitters. Now I'm gonna introduce some
important neurotransmitters in these different groups and I'm gonna mention some of their functions.
Don't worry too much about their functions right now because they do so many different things in
different parts of the nervous system that we'll come back to all of that in other videos. I just want to
briefly introduce the different important neurotransmitters in each of these classes. Starting with the
amino acids. Important amino acid neurotransmitters are this one which is called glutamate. Glutamate.
This one which is called gamma-aminobutryic acid which pretty much everybody just shortens to GABA.
G-A-B-A for gamma-aminobutryic acid. This one which is glycine. Glycine. Glutamate is the most
common excitatory neurotransmitter of the nervous system.

Let me just draw a big plus sign above glutamate here because most of the time in the nervous system
when a neuron is releasing a neurotransmitter that it's exciting its target cell most of the time that
neurotransmitter is glutamate because it usually causes depolarization of target cells so that it excites
them. GABA and glycine are the most common inhibitory neurotransmitters of the nervous system. Let
me just write some big minus signs above GABA and glycine because they usually cause hyper
polarization of target cells and inhibit those target cells. GABA is the most common inhibitory
neurotransmitter in the brain while glycine is the most common inhibitory neurotransmitter in the spinal
cord, so that the amino acid neurotransmitters are really involved in most functions of the nervous
system. Pretty much if you think of anything the nervous system is doing at some point in the chains and
networks of neurons glutamate, GABA and/or glycine are probably involved in moving information
through those networks. There are many important monoamine neurotransmitters but I'm just gonna
mention these five that are arguably the most important. The first one here is serotonin. Serotonin. The
next one here is histamine. Histamine. The next one is called dopamine. Dopamine. Then this one is
epinephrine. Epinephrine. Right next to epinephrine is its close cousin norepinephrine. Norepinephrine.
All five of these are monoamine neurotransmitters but these three dopamine, epinephrine and
norepinephrine are also called catecholamines.

The monoamines play a lot of different functions in the nervous system and in particular a lot of
functions of the brain including big things like consciousness, inattention and cognition or thinking, and
emotions or us having feelings. Norepinephrine is also released by some autonomic neurons in the
peripheral nervous system. Many disorders of the nervous system involve abnormalities of these
monoamine neurotransmitters systems, and many drugs that people commonly take affect the
monoamine neurotransmitters.

There are many important peptide neurotransmitters including a group of peptide neurotransmitters
called the opioids. Opioids. The opioids are a group within the bigger group of the peptide
neurotransmitters. This one is one example of an opioid. This is endorphin. Endorphin. The peptide
neurotransmitters play a role in many functions of the nervous system but the opioids in particular play
a big role in our perception of pain. A number of pain medications affect the opioid neurotransmitters.
Last but definitely not least are the other neurotransmitters.

Usually when there's an other category of anything that means it's not very important but in the case of
neurotransmitters there are some really important neurotransmitters that are not amino acids,
monoamines or peptides. For example, this neurotransmitter right here is called acetylcholine.
Acetylcholine. Acetylcholine is definitely one of our most important neurotransmitters. It does a number
of functions in the central nervous system, and then in the peripheral nervous system it's released by
most neurons in the autonomic nervous system. Let me just right ANS for autonomic nervous system
and it's released by neurons called motor neurons that synapse on skeletal muscle and tell our skeletal
muscle to contract to make us move.

Again, don't worry too much about these functions because in other videos we'll go more into the
structure and the function of the nervous system and talk about specific neurotransmitter pathways. I
just wanted to introduce the different types of neurotransmitters here and start to give you a feel for
the huge variety of functions all these different neurotransmitters have in the nervous system.

I want to talk about the types of neurotransmitter receptors. Neurons are often referred to as excitatory
or inhibitory, but more accurately it's the synapse that's excitatory or inhibitory, and even more
specifically, it's the combination of the neurotransmitter that's released at the synapse and the receptor
that it binds to on the post synaptic membrane. Because many neurotransmitters can bind to multiple
types of receptors so that the neurotransmitter can sometimes be excitatory and it can sometimes be
inhibitory to the target cell so that this axon terminal might be releasing this neurotransmitter here at
the synapse and perhaps when it binds to this purple receptor, that causes an excitatory potenetial in
the target cell, but if it binds to this orange receptor on the post synaptic membrane, that would cause
inhibition of the target cell, would cause inhibitory potential.
When the target cell is another neuron, excitatory or inhibitory synapses can be scattered around all
over the surface of the neuron. Or there are many neurons where the dendrites are receiving
predominately excitatory synapses so that there can be a large number of neurons synapsing on the
dendrites and releasing neurotransmitters that will cause depolarizations in the dendrites. So let me just
draw little purple pluses in here to represent that these are excitatory synapses. And then many neurons
like this will have more inhibitory synapses on the soma. So I'll just draw some little orange minus signs
here to represent that these could be inhibitory synapses on the soma.

And then often neurons have synapses on their axon terminals so that other axon terminals are
synapsing on the axon terminal of the target neuron and these will often be a mix of excitatory and
inhibitory synapses. And there's a big variety in how the synapses are set up on neurons. And there
would be a mix of some excitatory and inhibitory synapses at all these locations. But for neurons that
are set up like this, kind of a general way of thinking about how information would flow to the neuron is
that they can receive lots of excitatory input through the dendrites, causing depolarizations to spread
down the dendrites into the soma. But then if these neurons are inhibiting the soma, that can block
those depolarizations from reaching the trigger zone to trigger an action potential.

And then when action potentials are conducted from the trigger zone down the axon to the axon
terminal, the excitatory and inhibitory synapses on the axon terminal can increase or decrease the
amount of neurotransmitter that is released when an action potential reaches the axon terminal. So that
there can be fine tuning of the output of the neuron at multiple levels all the way from the dendrites
through the soma and to the actual individual axon terminals, can have their output turned up or turned
down in response to the information flowing in from all these synapses. So that one way you can
categorize synapses is if they're predominately excitatory or predominately inhibitory. But there are
some other big differences in neurotransmitter receptors and how they pass information from
neurotransmitters in the chemical synapse to the target cell.

So let me just draw a big axon terminal here that's releasing neurotransmitter into the synaptic cleft.
And this will be the post synaptic membrane of the target cell. And I'm gonna draw the two big types of
neurotransmitter receptors here. Let me draw this one in grey with its little receptor to bind to the
neurotransmitter. And I'll draw this other one in yellow over here with its little pocket to bind to its
neurotransmitter. So this first type of neurotransmitter receptor is called ionotropic. And ionotropic
neurotransmitter receptors are ligand gated ion channels. So they have ion right in the name. And when
their ligand binds to their receptor, which in this case is their neurotransmitter, they open and allow
certain ions to pass. And when the neurotransmitter leaves the receptor, then they close and they don't
let ions pass through anymore.

The ionotropic neurotransmitter receptors cause graded potentials when they're activated, which have a
rapid effect on the potential of the near by membrane that is brief and local. The target cell will usually
be excited if the activated ionotropic neurotransmitter receptor allows sodium or calcium ions to pass
because they will usually flow into the neuron, bringing their positive charges in and causing
depolarization. Or the ionotropic neurotransmitter receptor will usually cause inhibition of the target
cell if it allows chloride or potassium ions to pass. Chloride ions will usually flow into the neuron,
bringing negative charges in, making it more negative inside and potassium ions will usually flow out of
the neuron, carrying their positive charges outside and also making it more negative inside. Now the
other big class of neurotransmitter receptors are called metabotropic. And these are not ion channels.
Instead, when their neurotransmitter binds to the receptor, they activate second messengers inside the
neuron. And there are a number of different types of second messenger systems that can be activated
by metabotopic neurotransmitter receptors.

And these second messengers can do a lot of different things. They can go and effect the behavior of ion
channels, causing them to be more or less active. Or they can change the activity of proteins inside the
neuron. And some can even effect the activity of genes and change the pattern of gene expression inside
of neurons. When these metabotropic neurotransmtter receptors are activated, the response of the
target cell occurs more slowly than it does with activation of ionotropic neurotransmitter receptors, but
the effects may be larger and they may be more widespread because there can be amplification through
these second messenger systems. The effects of activation of these second messenger systems by
metabotropic receptors may involve just brief excitation or inhibition of the target cell, or it may cause
longer lasting changes to how the target cell behaves, either when it's at rest or when it's responding to
input.