[Music] >>STOWELL: There are so many unanswered questions
in intro psych textbooks about how neurons work, uh. I wanna emphasize a few main points about
how neurons work so that you can help your students better understand how neurons work,
uh, because you think about the importance of what neurons do, which is: they’re the
basis for our behavior, right. We, we don’t behave without neurons, so
they’re a crish- a crucial part of our behavior and what we do. So, uh, first of all, how many of you a
re
just – you don’t feel very confident in your ability to teach how neurons work? How many of you are just like, ‘I just don’t
quite know how it all works myself’, and you know, you know it at the level of the
intro psych book and you can convey that, uh, and students seem ok with it, but maybe
I can give you a few more, uh, details that will help you – something’s gonna click,
ok, in this part of the lecture. Something’s gonna click for you that’s
like, ‘Oh! I didn’t know that!’ ok, and that m
akes sense and it finally fills
in a missing piece that maybe you didn’t have before. So there’s our, our favorite neuron, ok,
just the classic motor neuron, ok. Neurons come in a wide variety of sizes and
shapes, but um, that one looks like the classic motor neuron with all the different parts. And when we talk about action potentials,
um, we are talking just about from here to the end, ok. We’re not talking about the dendrites and
the cell body – that’s a different type of potential that occur
s. But ultimately when we have an action potential
which is this neural signal that’s sent up to a hundred meters per second in some
neurons, we’re talking about the axon, ok. That’s only – the only place where the
action potentials occur. So maybe you didn’t even know that, ok. And note that some of these neurons have these
purple hot dog buns wrapped around them, ok, which is the myelin sheath, and we’ll talk
a little bit about that later. If you zoom in on this membrane of the cell,
ok, you f
ind this phospholipid bilayer; it’s a fluid, flexible membrane, but there are
proteins embedded in this membrane. They are – some of them act as channels
or pores that allow only certain ions to pass through and only at certain times, ok. So, it is these, it is these proteins that
are crucial for the functioning of neurons, because normally the membrane is impermeable
to ions. They are not allowed to cross. We can measure the electrical activity of
neurons by placing a very tiny electrode just i
nside the membrane, and we can amplify those,
uh, electrical signals on a computer and, and, and observe electrical changes over time
in neurons. And here’s an actual microelectrode, uh,
approaching the cell body of a neuron, ok. You can pierce the membrane and we find that
at rest, the inside of a neuron is negative relative to outside by a little bit, ok, by
about seventy millivolts, which, you know, you get enough of those together, you can,
you can measure, ok. So, I like to start with why,
ok, neurons
have a negative charge inside the membrane at rest, ok. And – does anyone wanna offer an explanation
for, oh, you know – why do neurons have this charge? What good does it do neurons to be, uh, charged
even at rest when it’s not sending a signal? What’s the function – the purpose? Why is it negative? Well, the result, ok, of having this resting
potential is just like, uh, you know, go back to your own high school experience. So you talked about like, potential energy
and kinetic ener
gy, ok. Potential energy s- means that work can be
done. Well essentially by having a charged, charged,
literally a charged neuron, it can do work, ok. It can do work. And it doesn’t have to charge up the battery
before it fires an impulse, fortunately. Because, you know, say that baseball is coming
right at your head, you have to act quickly, ok. You don’t your brain – you don’t want
your brain to have to charge those neurons – ok charge em up, ok. Now make your head move out of the way – no. T
hat’s too late, right? So neurons are charged and ready to fire,
ok. They have potential energy. And the reason for that is a number of factors. So you know the sodium-potassium pump, right? It’s in the membrane of neurons, it’s
uh, always working, it’s always cycling in and out – these, these charged ions,
ok. And ions are nothing more than a charged molecule. In fact, uh, two hydrogen atoms meet. One of them says to the other, ‘I think
I’ve lost my electron’. The other hydrogen atom says, ‘Are
you sure?’ The first one says, ‘Yes I’m positive!’ [Laughter.] Ok, alright, that’s good you got that, ok. So this pump, ok, this is a section of the
axon. The tube, ok, we’ve just taken a little
cross-section of it. And we’ve got a little pump that’s working
here and that pump will pump out sodium ions – three of em – for every two potassium
ions that come in. And the most important result of this pump
is that it creates differences in the concentrations of these ions. So where do you start to
accumulate more sodium? Outside of the cell, right. And where to do you start to accumulate more
potassium? Inside the cell. Now, normally at rest, this cell membrane,
uh, does not allow these ions to leak acrost. And this re- this pump results in a pretty
large concentration difference between the inside and outside of a neuron. Uh, there’s about ten times as much sodium
outside than there is inside – there’s a lot more sodium out there. And there’s about twenty times more potassium
inside than
there is outside. So you’ve got a lot of sodium outside, and
a lot of potassium inside. And at rest, for the most part, ok, these
ions do not cross the membrane except for some potassium, which I’ll mention shortly,
ok. So, here’s a, a figure that shows these
proteins in the membrane which act as pores or channels which allow these ions to pass
through, but only at certain times, ok. So for the most part – sodium, there’s
a lot of it outside, and why does it want to get inside? >>PARTICIPANT: [
unclear] >>STOWELL: Ok there’s actually two reasons. One is that if it’s negative inside the
cell, a positive charge will be attracted to it, ok, that’s only – that’s one
reason, yes. What’s the other reason that it wants to
get in? >>PARTICIPANT: [unclear] >>STOWELL: It will in just a minute. There’s a l- ok, it’s the law of diffusion,
ok. Which is if there’s an area of high concentration,
and an area of low concentration, it’ll try to spread out and equalize, right? It’s just like if you spray
a drop of perfume
or something, eventually it’ll diffuse throughout the whole room, ok, fill the available space
in equal concentration. I like to uh, actually take a drop of food
coloring and put it in a cup of water and not even stir it, and before long, it’ll
be completely, uh, the same color throughout the solution because of diffusion. Atoms bounce around and they like to spread
out from each other, ok. So there’s two reasons why sodium wants
to get in: because it’s negative inside, and be
cause there’s a lot more outside than
inside and it’ll just try to diffuse and equalize. This membrane of the axon, uh, possesses what
is known as selective permeability, which means that it only allows certain ions to
pass at certain times. Another reason why it’s – uh, just forget
this one. I, I hate to see it in even my biological
psychology book. Ok, that’s, that’s why you got these large
negative proteins inside the cell and that makes it negative. That’s not the main reason why it’s negati
ve
inside the cell, ok. The main reason why it’s negative inside
the cell at rest is because the membrane is leaky to potassium. And potassium, being positively charged, as
it leaks out of the cell, you lose some positive charge – enough that it becomes negative
inside the cell. That’s really the main reason why it’s
negative – because at rest, neurons are leaky to potassium, and when that positive
charge leaks out, relatively speaking, it’s more negative just inside the membrane than
it is outs
ide,ook. That’s the main reason why it’s negative
at rest, ok. Yes. >>PARTICIPANT: I have a question. So, if potassium is leaky, it’s positive
but there’s more sodium outside, why does the potassium want to leak out? If we’re just talking about location. >>STOWELL: Because at rest, neurons do not
let sodium cross the membrane. Sodium’s not moving any– yeah if you open
up those sodium channels, guess what happens? Ooh. You got an action potential, ok, we’ll get
to that in just a minute, ok. But b
ecause at rest, only potassium is leaking
out. It carries the positive charge with it and
it makes it more negative. Now it only leaks out enough until it gets
so negative that those potassium charge is like, ‘oooh, I still like that negativity,
I, uh, do I wanna leave? Ok, there’s a lot more of us in here, we
want to spread out, but, oooh, but it’s negative inside.’ You know, and the more they leave, the more
negative it gets, right? There’s a balance there, and, if you just,
if you just c- tak
e a membrane that only allows potassium to cross and not sodium, you can
measure a potential difference of about negative seventy-five millivolts, ok. Just because that pat- potassium leaks out,
until it says ‘eeeeeh’, and finds the balance of what pulls it back in. That’s where – that’s what at rest,
that’s what it sits. Great question. Other questions? Yes. >>PARTICIPANT: Does the toilet, um, [laughs]
analogy work? >>STOWELL: For the all-or-none principle? >>PARTICIPANT: Yeah [unclear]. >>STOW
ELL: Yes, it does. >>PARTICIPANT: Because I mean, I’ve been
using it but I just want to make sure that like – >>STOWELL: Yes. >>PARTICIPANT: [unclear] - as a biological
psychologist [unclear]. >>STOWELL: Yep. It works. That’s good. Uh, ok, just very quickly. Um, a neuron will either fire an action potential,
or not, ok. There’s no in-between, ok. Once you reach the threshold, boom. It sends that all the way down the end of
the axon every time. It’s kind of like flushing the handle of
a toilet, o
r, the handle of a toilet. If you don’t reach that critical amount
of pressure, the toilet doesn’t flush. But once you reach it – boom! It flushes every time, ok. And the other great thing is that it takes
time to fill, right, ok. So it’s like neurons, you gotta wait, recharge
just a little bit – ok now you can have another one, ok. The other thing I want to emphasize is that
when ions are moving across the membrane, it takes a tiny, tiny amount. And the overall concentration, ok, after you’ve
o
pened up these channels and let some in and out – the overall concentration has probably
changed by less than one ten-thousandth of a percent, ok. When you let neurons open their channels and
ions come in and out, it takes very few of them to create these electrical currents,
ok. In other words, you still have tons of sodium
out there and you still have tons of potassium inside the cell, ok. And only over a very long period of time will
that run down, if you don’t ever recharge it, ok. Alright,
so we – >>PARTICIPANT: Can I ask you [unclear]? >>STOWELL: I’m gonna skip over that bit. Yes. >>PARTICIPANT: Um, so, what makes it negative
inside besides the leaking, is it the negative chloride ions? >>STOWELL: Chloride ions are f- both inside
and outside. There’s actually more chloride ions outside
the cell than there are inside. Uh, but chloride plays very little role in
the electrical potential of the membrane. >>PARTICIPANT: So what makes it negative then,
if you’ve got all these positive
ions? >>STOWELL: Because it’s the relative – remember,
ok – it’s relative inside to outside. If I take some positive charge out – >>PARTICIPANT: Ok. >>STOWELL: – it becomes more negative relatively
speaking to the outside. >>PARTICIPANT: Relative, it’s relative. >>STOWELL: Relatively speaking, yes. >>PARTICIPANT: Ok. That’s what I needed to know. >>STOWELL: In fact, if you look at the overall
electrical, um, you know, the number of positive and negative charges in the whole system,
they’re equal
. It’s electrically neutral. In the whole system, it’s electrically neutral. It just so happens that you get enough of
these positive charges just at the pla- just along the membrane leaking out that you can
detect a difference, ok. But in the whole system, you, you, you’ve
got plenty of negative charge laying around. >>PARTICIPANT: Ok. >>STOWELL: Just as much as you put table salt
in. You’ve got sodium, and you’ve got a chloride
ion. Just as many in there, ok. Great question. Other questions? O
K, I’m starting to get that glazed look
– oh no. You’ve already lost me, ok. Alright, so this just shows – and once again,
this is at a single point of the axon. This is not the distance of the axon, this
is at a single point over time; the electrical changes that take place as the electrical
impulse passes this single point, ok. Meaning that you have to have these changes
taking place at every part of the membrane, all the way down the neuron. But we’re looking at just one spot, this
is what th
is represents. So, over time, we have a neuron at rest, which
is about minus seventy millivolts. We do something – and this is the big question
that I always get – ‘What starts the process?’ Ok, and it’s kind of like the chicken and
the egg. Well what do mean? You know, it’s like, you have to start somewhere
in the cycle, right? Because upstream, you’ve got input from
other neurons, or you’ve got sensory organs that are causing changes that ultimately cause
this neuron to become more positive to
a point that these changes will take place, ok. The action potential will be triggered. So that’s always a question that comes up. But, uh, what accounts for – ok there’s
a threshold of excitation – what accounts for the spike? What happens at the level of the membrane
to make it more –become more positive inside the cell? >>PARTICIPANT: Sodium [unclear]. >>STOWELL: Sodium comes in first, ok. So, there’s our resting potential. If you let sodium in, you’re letting positive
charge in right? It’s
gonna become more positive inside the
neuron. Simple enough. You let positive charge in. Those ion channels in membrane open, ok, the
ones for sodium and they let sodium in. They don’t stay open very long, ok, they–
quick to open, but they’re also quick to close. The potassium channels will also open, but
they’re a little slower. Slower to open and slower to close. So, this is why on the up-shoot on the action
potential, the depolarization phase, sodium is rushing in, but then the sodium channel
s
are closing, and by now, ok, these delayed potassium channels are opening. Potassium- I mean, excuse me, sodium wants
to go out. Ares- bleh. Sodium wants to go in because there’s a
lot more outside than inside. Potassium wants to get out, even more than
it does at rest, so those channels open up, and when you let positive charge out – this
is gonna be, do you have a ques-? [Unclear.] Well you let positive charge out, it becomes
relatively more negative inside the cell. It even overshoots that
a little because those
sodium – those potassium channels stay open longer and they let a lot of it out, ok, and
during that period of time where it’s below resting threshold, it’s called hyperpolarized,
and it’ll be harder to reach the threshold during this phase, ok. This is a refractory period, if, if you talk
about that, but- >>PARTICIPANT: [Unclear.] >>STOWELL: – that’s a refractory period,
uh. Actually, this section right here – you
cannot have another action potential. That’s the absolute
refractory period. There’s no way you can open those sodium
channels again, because once they’re shut, they stay shut tight, just for a little bit. How long does this take place? How, how long does it take for the sodium
to rush in, the potassium to rush out – and by the way, these are charged particles, right? And when you move charged particles, what
do you get? You’re gonna get electrical currents. Yeah, that’s what we’re measuring. We’re measuring the electricity, but electricity
is nothing
more than the movement of charged, charged parti- mol, molecules. So, you let positive charge move in, it becomes
positive. You let other positive charge out, becomes
more negative again. And once again, the total difference in the
concentration of these two ions has barely changed at all, ok. Which means, can you have another action potential
after this one? Sure, yeah. There’s still plenty of ions that wanna
move, ok. You can have thousands of these action potentials
before ultimately, you’re
gonna, you’re gonna equalize the concentration, and if that
happens then they’re not gonna move and it’s, it’s not gonna work. So what is constantly working in the background
to keep these ions different concentration? What’s, what’s working to keep those concentrations
different? >>PARTICIPANT: The sodium-potassium pump is
always – >>STOWELL: The sodium-potassium pump is always
working in the background to keep these ions separated to that they’ll move when you
open up the channels in the membr
ane. The sodium-potassium pump does not have anything
to do with this, ok. The pump does not recharge, or reset – no. It’s always working in the background. But this v- occurs in about a millisecond,
ok. [Laughs.] There’s no was the sodium-potassium pump
is gonna keep up with that, ok. It’s constantly working in the background. Uh, skip over that. So, I teach my students a song: ‘I’m A
Little Neuron’. Ok, it remembers the, the main points of the
action potential, ok. And I know I gave you a lot
more than what
you pr- probably even need, students even need to know in intro psych, but this helps
them remember the, the main points of an action potential, ok. It’s to the tune of ‘I’m A Little Teapot’,
ok. [Singing]: I’m a little neuron short and
stout, here is my dendrite, here is my spout – [Talking]: Now, I couldn’t get axon to fit
in there, so the spout is the axon, ok. [Continues singing]: When I reach my threshold,
here me shout, let the sodium in, potassium out. Ok, so all together n
ow with me, Ok. Huh, you didn’t know you’d be singing
today. Ready? >>PARTICIPANT: Let’s go. >>ALL [SINGING]: I’m a little neuron short
and stout, here is my dendrite, here is my spout. When I reach my threshold, here me shout,
let the sodium in, potassium out. >>STOWELL: Ok, nice job, well done, good job. Alright, so they get that stuck in their head,
and they’re like, ‘Well, yeah, just remember that sodium rushes in, and potassium rushes
out, uh when you reach the threshold, Ok. And it’s happe
ning in the axon, ok. Alright, so I’m gonna skip over that, uh,
I’m gonna skip over that one, ok. We know that this one is false. It’s not the sodium-potassium pump that
gets everything back to where you started, ok. It’s just the opening and closing of ion
channels, that’s all it is, ok. So, then the mystery of how it spreads, ok,
the mystery. The mys- we’re just gonna leave the mystery
of how everything gets started. You can just simply say, ‘Well, another
neuron stimulates it.’ And that’s tru
e, ok. Once you’ve activated, ok, the beginning
of the axon, this is how it’s perpetuated: Those channels are sensitive to the voltage
of the membrane. And if you raise it to about, uh, maybe minus
fifty or minus sixty, the channels will open. That’s what they do. They’re sensitive to the voltage of the
membrane. So let’s say that we get the first few to
open up, and now you, all of you represent a part of the axon membrane. You are all ion channels, ok, and you’re
all gonna be sodium channels,
‘cause that’s easy enough to, to do, ok. And, usually my room is wider this way than
it is that way, but, uh, we can still do it, ok. Let’s say that you’re right next to the
cell body. First part of the axon: your sodium channels
open up. I want you to open your hands like this, like
a little touchdown thing – but, but just the ones running along this edge, ok. Right there, ok. So now we’ve opened up some sodium channels
and we’re gonna let a little bit of sodium ions in here. Now, at the neighb
oring part of the membrane,
it says, ‘Ooh, it’s starting to get a little more positive around here, right?’ Because we’re- they’re letting positive
charge in. So they’re like, ‘Ok, well I, I’m gonna
open up!’ Ok. So now, this row: open up your sodium channels,
ok. And sodium rushes in here, and the neighbors
say, ‘Oh, it’s getting more positive’. And – boom! You know, they go up, ok. Now you- you’re right, your hands don’t
stay op- open very long, because sodium channels are really fast at this,
ok, uh. But we let more positive charge in here, and
the next ones open up, and so now we’re gonna do the wave all the way across, ok. Because this is how it works in a neuron. It d- does the wave. Ok, so on your mark, get ready, go! T-t-t-t- yeah. [Participants laugh]. >>STOWELL: Ok. Can we go backwards? Try it again. Mm- backwards, yeah. You guys are good at this. Ok. [Participants laugh]. >>STOWELL: Alright. That’s how it spreads. That’s how it spreads. Now, what if there was a way that – in
stead
of having every neighbor detect the change and open up, what if we could somehow skip
a few and just kind of regenerate that every so often, ok? Do you think that’d be a little bit faster? It is. In fact the way that we do that is myelin,
ok, uh. Essentially the act- the action potential
gets regenerated only at the nodes between the myelin. There’s enough, there’s enough electrical
changes up here that it can passively spread – just like through a wire, ok – that
these, uh, these channels
here can still detect it. They’ll open up, they’ll let enough positive
charge in that that can passively transmit through a little section of the neuron, get
regenerated at each point, ok, so it’s much faster, uh. I don’t think I’ll do it here, but in
class I would have a competition, uh, in passing two brains, ok, two squishy brains, uh. One neuron – I’m, you know, I might go
from front to back in this class – you’d have to pass it hand to hand to your neighbor. Every single person all the way
down the line,
uh. The other, the other pathway – I would say
‘Ok, you can toss it every three people’, ok. And then I just have a little race and guess
which one wins every single time? OK. The one that can pass it every, every few
people. So, this type of neural transmission is faster,
uh. A real life recognition of that: how many
of you have ever stubbed your toe before? Ok, yeah, sure. A lot of us – everyone’s, right? Stub your toe, you’re like ‘Oh, I stubbed
my toe’, and then you might swe
ar, ok. And then realize that, ‘Oh it didn’t hurt
so bad, did it?’, ok. Or the opposite, where it’s like ‘dink’
and you’re like ‘that was nothing. Woooaaahh!’ Ok, and then before, you know – why do you
feel it but not the – why do you feel it right off the bat, but why does it hurt – or
not – until a few seconds later? Different pathways for different messages. The pathway of touch goes through large neurons
that are myelinated, ok. Very quickly, you know, the six feet up to
my brain – oh you, y
ou’ve hit something. The pain neurons are small and unmyelinated
and it takes longer to go six feet – noticeably longer to go six feet – than it does with
myelin. So you feel it, but you don’t know the pain
message until maybe a second or two later, cause it’s about ten times faster when it’s
myelinated. >>PARTICIPANT: So, with MS – >>STOWELL: Yes. >>PARTICIPANT: – when you have myelin go
apart, the, the actions caused in the, the handicap is that they’re losing signal. >>STOWELL: The, you lose
the signal because
without the insulation, it, it spreads too much that it can’t get to the next node
to regenerate, which means you could have a problem in myelinated neurons, which supply
muscles or sensory neurons. So it’s unpredictable where you’re gonna
see the deficit. Could be vision, could be in moving, ok, but
yeah. MS destroys the myelin, which is bad, ok. So we’re right at 10:30, right when I wanna
wrap up. The, the points of the neuron then, ok. The resting potential, the fact that i
t’s
negative inside, is primarily because it’s leaky to sodium at rest, ok. It lets out a little – excuse me, leaky
to potassium at rest. It lets a little bit of the potassium out,
so that relatively speaking, it’s more negative inside than outside, ok. The sodium-potassium pump is not, ok, what
immediately restores the neuron to its resting potential, ok. It’s simply the closing ok these channels. And it doesn’t take very many ions moving
to create these electrical changes, ok. And you can have
thousands of action potentials
before the battery essentially runs down, ok.
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