Good morning. Thank you. So, I want to continue today on the
theme of neurobiology. Last time we spoke about the action
potential mechanism. Today I'd like to go from action
potential to the synapse. But let me briefly remind us what we
say. So, I'm going to give section zero a recap here.
The relevant things that we said last time was there's a membrane
potential which at rest is about minus 70 millivolts as the membrane
potential, and that's what we work with. That membrane potential is
set up by concentration gradients. More calcium, more potassium on the
inside. More sodium on the outside. More calcium on the outside. And
I'm also going to mention chloride, there's more chloride on the outside
at 116 millimolar, four millimolar on the outside.
These concentration gradients are set up by various different pumps.
They're there all the time. Then we have this resting channel.
So, here we have transporters.
We have a resting potassium channel. It means that it's open all the
time. It's not activated by anything.
That allows potassium to leave. Potassium leaves until it builds up
this membrane potential about minus 70. At that point it is
electrically unfavorable for more positive charges to go out into the
more positive environment. Notwithstanding the greater
internal concentration. And we reach an equilibrium
potential of minus 70. We then have some voltage-gated
And the voltage-gated channels come in two flavors here.
We have the voltage-gated sodium channel. The voltage-gated sodium
channel opens itself up around minus 70. Oh, sorry,
around minus 50. So, if you can get up to minus 50
it opens up. Then your sodium rushes in. It shifts the membrane
potential from minus 50 to zero to plus 50.
The channel shuts. Somewhere around plus 30 or so
opens the potassium channel, the voltage graded potassium channel,
and allows the potassium to rush out and restore the resting potential.
The effect of this is that, if this is zero here, we have
a resting potential. If we climb up a little bit above it
we shoot up and then we come back down. And then a millisecond or so
later another action potential could go down that same neuron.
And, last of all, if we look along the length of an axon,
an action potential here causes charges to migrate over which
launches an action potential here which causes charges to migrate over
which etc., etc. propagates an action potential down
the length. It's a beautiful system.
And then the very last thing was that by insulating this we were able
to make the conduction velocity go faster by effectively making the
effective length be shorter there being a whole bunch of electrically
insulated regions. So, that's it. It's a beautiful
piece of engineering. How do we know any of this is true?
As an interesting side point,
I might just mention that when this was worked out,
this was worked out by two folks called Hodgkin and Huxley.
Hodgkin and Huxley won a Nobel prize for this beautiful work on
this squid giant axon which is the fastest axon that there is.
And here we're not talking about the giant squid somebody raised last
time. It's an ordinary squid. It has one big fat axon. It's
sufficiently big that you can just like stick a wire in the middle of
it and all that. It's a very big axon.
It's a very, very high diameter axon.
And they were able to measure these things electrically.
And on the basis of the electrical measurements they made in different
kinds of solutions, they were able to infer the
existence of sodium channels and potassium channels.
But this all happened mid 20th century. And they certainly
couldn't see any. They couldn't clone them.
They couldn't see anything. And so the notion that there were
individual molecular channels that swung open, did all this stuff was
an indirect inference, maybe kind of a little bit like
Mendel's inference of a gene or Sturtevant's inference
of genetic maps. But more recently people have come
along with an extraordinary technology, also these people won a
Nobel prize for this because it was way cool, which is called the Patch
Clamp. The patch clamp is the following ridiculously simple
technology. Suppose I were to make a glass pipette.
So, this is a cross-section of a glass pipette.
So, it goes around like that. And I could bring it up really
tight up against the membrane. And suppose I did it in such a way
that I could get a really great seal and I just have a teeny patch of
membrane. Suppose that teeny patch of membrane had just
one channel in it. And now, so this is a pipette,
suppose I were to rip off that patch of membrane from the cell,
poor cell, and have a glass pipette with a little patch of membrane on
its end with a single isolated ion channel. Now,
if I measured the current through this channel by putting it in an
appropriate solution, maybe I ripped off a resting
potassium channel, OK? If I put this in a potassium
solution and I apply a current, I apply a voltage difference, I
should be able to see a current. And you can actually measure a
current. Even more cool, if I do this and I've ripped off a
voltage-gated sodium channel, then it turns out that I ought to be
able to study its properties by changing the voltage on it and
measuring the current as a function of the voltage.
And, well, it turns out that if I do this I'm able to measure in resting
or in these voltage-gated channels current flows conductivities,
actually, what I'm really measuring is the conductivity of the channel
like this, I can see the channel opening and closing and opening and
closing quantily. I can measure quantily the
conductivity. That's not quantum mechanics. It's just quanta
measurements of the conductivity. What would happen if I had two
channels that had been ripped off? Now I'd see it go like this.
Well, maybe another one opens. Oops, now one closes. Now the
other one closes. And quite remarkably you can get
this. So, you can study single molecule, single molecular channels.
You want to know how this channel opens and at what voltage it opens?
Just dial in the voltage and see if it's open. Do you want to know how
long it stays open? Just turn it on and see how long it
stays open. It's really cool. You want to see if any other
chemicals could affect it, any ions, any other intracellular or
extra cellular chemicals? You can do it.
So, the ability to study isolated single channels came along with
patch clamping. And what it allows is a tremendous
study of the biophysics of individual channels.
And, whereas, before people had to look at the total conductivity of an
entire axon. Now they're able, and from that infer the behavior of
single channels, now what they can do is study the
behavior of single channels and synthetically build up a picture of
the total conductivity of an axon from its individual components and
see if the components we've identified are sufficient to explain
the behavior that we see. Anyway, that's patch clamping.
Lots of fun. So, now, what I want to turn now to is signaling
at the synapse.
So, we have our cell body here. It's got its dendrites on it.
Here's our axon. We've managed to get an action
potential started on it and it moves all the way down.
Now we get here to one of the synaptic terminals.
The electrical signal makes it all the way to the synaptic terminal,
but how does it affect the post-synaptic cell?
Well, let's get a close-up of that.
Here we go. Here's the synaptic terminal. We've got our action
potential coming. Action potential coming.
And then it gets here. Action potential's arrived.
I would like to release chemicals into the synaptic cleft,
the space between the pre and the post-synaptic cell.
I'd like to spill out chemicals that are neurotransmitters.
So, the pre-synaptic cell conveniently has vesicles,
little membrane-bound vesicles with prepackaged neurotransmitters.
OK? These prepackaged neurotransmitters have been
conveniently synthesized by the cell and they're just sitting there
waiting to be released in response to an action potential.
When the action potential comes, it causes these synaptic vesicles to
-- with the membrane. And in fusing the insides become
continuous with the outsides, here's a little fusion picture here,
and the neurotransmitters leak out. OK?
How does it do that, though, mechanistically?
How in the world does an action potential cause these vesicles to
fuse with the membrane? Well, somehow it's got to read out
electrical activity into some kind of a chemical activity
intracellularly. Here's what it does.
When the electrical signal comes down, remember originally the
membrane potential is negative, but when an action potential comes
by what does it do to the membrane potential? It reverses it.
It makes it positive inside briefly. OK? So, this is the sign of an
action potential, an AP coming down.
In this membrane we have us another voltage-sensitive channel.
This voltage sensitive channel is a voltage sensitive calcium channel.
OK? Who would like to design a voltage-sensitive calcium channel?
What should it do? What would you like to have its opening and closing
properties be? When does it open?
At a positive charge. So, when you get to a positive
membrane potential it swings open. And then what does it do?
Lets calcium move. Which way does calcium want to go?
In because it's more out. So, what's going to happen is in
response to the action potential calcium will rush in.
Now, calcium, you will recall, was in vanishingly small traces
inside, 0.1 micromolar we said. And influx of calcium is a very
serious matter and it is sensed by variety of proteins.
In particular, there is, floating around in the
cell, a protein here called a calcium-dependent protein kinase.
The calcium-dependent protein kinase
is a protein that is capable of putting a phosphate group.
Its kinase puts a phosphate group on other proteins.
So, the calcium-dependent protein kinase over here will go along and
catalyze the addition of a phosphate group to other proteins.
So, it will enzymaticly catalyze this. But it only does so in the
presence of calcium. So, when there's calcium in the
cell, the calcium-dependent kinase is activated and it runs around and
sticks phosphate groups on specific target proteins.
You know where one of those target proteins lives? In the vesicles.
The vesicles happen to be a target for this. So,
the vesicles have a protein on them. And in one of these extraordinary
coincidences in molecular biology, the protein on the synaptic vesicle
happens to be called, coincidently, synapsin.
OK? It's not actually entirely a coincidence that it's called
synapsin. It was named synapsin because it was found on the synaptic
vesicles, obviously. And so what happens is when the
action potential comes down it causes the calcium channel to open
in response to positive voltage. Calcium comes in,
actives at the kinase. The kinase phosphorilates synapsin.
And now the phosphorilated form of synapsin likes to bind to something
in the membrane. That's it. How many of you still
know what a Rube Goldberg machine is? Good. OK. This is one of these
just great, well, others of you should look it up on
the Web because they're just great cartoons, the Rube Goldberg cartoons
about the machine where the rooster crows startling the cat which tugs
the thing with causes this to flop which causes the eggs to go in the
pan which causes the thing to cook which causes whatever.
And I always think about these in terms of great molecular Rube
Goldberg machines. So, this is the Rube Goldberg
machine that gets this synaptic vesicle to fuse there.
OK? Good. Every bit of neurobiology has a molecular
mechanism to be explained like this. So, now let's go onto the next
bit. How does this signal gets sensed at
the next cell? What are we up to?
Number three. So, let's look at a specific junction.
Instead of looking at the junction between two nerve cells,
let me start with the junction between a nerve cell and a muscle
cell, the neuromuscular junction. OK? So, I've now replaced my
post-synaptic neuron by a muscle fiber here. This is
a muscle fiber. So, when it spritzes out the stuff
the neurons that innervate muscle fibers, actually,
I'm going to expand that a bit, the neurons that innervate muscle
fibers, here's the muscle, and I'll put it at some distance
here, muscle, spray out a particular transmitter in response
to the calcium influx. And that transmitter is called
acetylcholine, henceforth ACH.
Acetylcholine is spritzed out into the synaptic cleft and comes out.
And what do you think acetylcholine is going to do?
I've got to send the chemical signal to the next cell.
I've got to somehow send that signal to the surface.
It's going to bind to something on the next cell.
You know the deal, right? So, it's going to have to
bind to a protein on this cell. And, remarkably, what it binds to
is called an acetylcholine receptor. OK? Very reasonable stuff. An
acetylcholine receptor. The acetylcholine receptor happens
to be an ion channel, but it's not a voltage-gated ion
channel. It's not an ion channel that opens in response to the
voltage. It's an ion channel that opens in response to acetylcholine.
It's what we'd call a ligand-gated ion channel because it's gated by a
ligand, acetylcholine. So, this guy here is a ligand-gated
ion channel which, when acetylcholine binds to it,
swings open. And what it does is it allows in sodium.
Bingo. Now, when sodium comes in what happens? Action potential.
But what a second. This is a muscle.
All membranes have the machinery to
have an action potential? Nah, liver cells are pretty passive.
You do this to a liver cell it kind of sits there.
But muscle cells do have an action potential mechanism.
They do respond here like a neuron, an action potential. And so what
happens when I open up some sodium channels to the resting potential
of my muscle? What was the resting potential of my
muscle? About minus 70. What happens when I open up these
ligand-gated sodium channels? Sodium rushes in. What does it do
to my membrane potential? It makes it more positive.
What does that do? It triggers an action potential spreading
throughout the muscle. And because the muscle has an
action potential --
-- all you have to do is manage to get this going in a little patch of
the muscle and it spreads throughout the muscle fiber.
One neuromuscular synapse will be sufficient to activate the muscle,
in principle, because you have this action potential mechanism.
And then when the action potential fires in the muscle it actually
causes other channels to open, including some calcium channels.
The calcium channels cause calcium to come in. The calcium causes your
muscle to contract because of sliding of actins and myosins and
things like that. That's how it works.
That's this Rube Goldberg machine. All right. So, let's get ready.
Let's fire. Let's send a neuromuscular signal down.
Contract. Now here's the problem. I've got all this acetylcholine
sitting around in my synapse activating the ligand-gated sodium
channel causing sodium to come in, but I would like to relax my muscle,
please. What are we going to do about this?
I could trigger another channel,
and maybe it could be a delayed acetylcholine activated yeah,
dah, dah, dah, dah, dah, dah, that's possible. I could have it close
itself. These are all perfectly reasonable possibilities,
and we're going to refer them to the engineering committee.
What else? You could get rid of the acetylcholine some other way.
It turns out the latter is the solution here.
We would like to have some enzyme that chews up the acetylcholine.
How about acetylcholinesterase? So, let's put acetylcholinesterase,
ACHE, acetylcholinesterase in the synaptic cleft.
Then when I spritz acetylcholine it gets to the other side,
but very rapidly the acetylcholinesterase is degrading it.
And so it has a very short time of persistence in the synaptic
cleft. OK? That works. So,
that's how I run a neuromuscular junction. OK?
So, acetylcholinesterase is very important. Now,
again, as with many of the things I've talked about,
we really know these things are true when we're able to inhibit them in
different ways. So, I want to take a moment and
talk about drugs and toxins. Because they help us to probe these
different processes. Anybody ever have fugu?
Does anybody know what fugu is? What's fugu? It's a blowfish.
Right. It's a puffer fish eaten in sushi, and it's an extraordinary
delicacy. And why is that? Right. Because it's one of the only
sushis where you really have to worry about improper preparation,
not just giving you food poisoning or a stomachache or something like
that, but it's lethal prepared incorrectly. The reason it's lethal
incorrectly prepared is because the blowfish has a specific poison
called tetrodotoxin. So, if you eat sushi,
so, in fact, chefs in Japan require a license to prepare fugu
for customers. Every once, every couple of years
some famous actor or personality prepares his or her own fugu and
dies from it and it's in the papers. Seriously. This has happened to
people. They're able to do this. Anyway, tetrodotoxin, tetrodotoxin
is from puffer fish, fugu. Why does this stuff kill you?
It turns out that what tetrodotoxin does, this wonderful poison from
this sushi, is that it irreversibly binds, irreversible binding and
inhibition of voltage-gated sodium channels.
Why would this be an inadvisable thing to have?
Suppose you irreversibly bound to and inhibited your sodium channels,
your voltage-gated sodium channels, what would you be unable
to accomplish? An action potential.
This is ill-advised to be unable to accomplish an action potential.
You can imagine that what it leads to then is a paralysis and a very
serious one, and if it's irreversible this is not a good
thing. There are other things. Has anyone ever fired poison darts
in South American jungles? [LAUGHTER]
Well, if you have, you would have tipped them with
qurare. Qurare is used to make poison darts. What qurare does is
it reversibly binds, still not good, but it's a
reversible binder to the acetylcholine receptor and it
prevents it, it blocks the binding of acetylcholine.
Your acetylcholine receptors, therefore, cannot respond to your
acetylcholine. What will that do?
A flaccid paralysis because you're unable to move your muscles.
So, if you were trying to shoot prey in the forest and you send the
poison dart that has qurare, it will cause the animal to then
flop over. Yes? Snakes. Ooh,
what kind of snakes? Venomous steak snakes,
yeah. [LAUGHTER] Like bungarus snakes, the really poisonous ones.
So, it turns out, great question, that they make something called
alpha-bungerotoxin. Venomous snakes,
next thing on my list, exactly. The only improvement they
make here is that this is an irreversible binder to the
acetylcholine receptors. Very impressive stuff. Different
stuff. We'll come back to jellyfish. But, basically,
everything you know out there that's noxious is being noxious in some way
that affects molecular biology. Not all of it affects the nervous
system. Those of you who like to collect mushrooms may wish to avoid
amanitas mushrooms. They make amanitas.
Amanitan is an irreversible binder that affects polymerase,
RNA polymerase. Not a good thing to lose either. So,
all parts of this course have interesting poisons that will affect
it but we'll focus on the poisons effecting neurobiology today.
And then there's a human made thing. Do you remember the, well, those of
who have heard of World War I, nerve gas or, in particular, who
remember the attack in the Tokyo subways with sarin,
a particular kind of nerve gas. Do you know what that stuff does?
It is a potent inhibitor of the enzyme acetylcholinesterase.
What would happen if I inhibited your acetylcholinesterase?
The muscles tense up and I'm unable to relieve them because,
just like I was doing there, because my acetylcholine is not
broken down in the synapse. So, this is a nice menu of
interesting poisons and fun facts to know and tell and good things to
avoid. There are more drugs and things that we can come back to.
So, now let's talk about, let's move onto other synapses.
Let's take a look at nerve-nerve synapses.
So, we looked at a nerve muscle
synapse. What were the properties of this nerve muscle synapse?
Well, it had the property that a single neuron innervates a single
muscle fiber. All right? This was a one-to-one single fiber,
sorry, single neuron, single fiber.
When we get to nerve-nerve synapses, they're more complex. Multiple
different nerve terminals may synapse upon the same neuron,
as I indicated last time. There might be a thousand different
nerve terminals synapsing on the dendrites of a postsynaptic cell,
but let's look at one of them for a moment. Then we'll come back to how
a thousand can work together. So, here's one.
And here's my dendrite that I'm synapsing on here.
The nerve terminal releases into, sorry, into the synaptic cleft some
neurotransmitter. It turns out there's a wide variety
of neurotransmitters that get released while the neuromuscular
junction involves acetylcholine. One example that might be involved
here is something called glutamate. What's glutamate?
It's an amino acid. Glutamic acid. It's the ion of
glutamic acid. That actually is a neurotransmitter.
Ever have monosodium glutamate. Does anybody get a headache from
monosodium glutamate? I do. That's because it's a
neurotransmitter. It messes with brain chemistry.
So, glutamate. Glutamate is released.
And what is does is there is a channel on the post-synaptic cell
that binds glutamate. And it, too, is a ligand-gated ion
channel. And it could be, for example, a sodium channel.
Other neurotransmitters might use other channels.
What happens if I spritz some glutamate on a dendrite of a cell
that has a glutamate-activated sodium channel?
What will happen in that dendrite? Sodium will rush in causing the
membrane potential to become depolarized and then positive and
then causing an action potential? No. It turns out that that last
bit doesn't happen because the dendrites don't have the action
potential machine. The action potential machinery is
interestingly confined to the axon. It's not found on the dendrites.
So, when we spritz with glutamate, what will happen is if this is a
glutamate-bearing synaptic terminal the membrane potential here will
become locally positive. But it is not an explosive
regenerative action potential because there are no voltage-gated
sodium channels that are going to open in response to that local
depolarization. So, it became a little positive
over in this corner of the neuron. Now, if it gets a little positive
over in this corner of the neuron, you know, it's going to draw some
negative charges from over here, right, to offset that local
positivity. But if it's just a local little patch of positive then
it draws a little bit of negative charge. But is that going to be
enough to depolarize over here? No. So what do you want to do?
Have more. Suppose I have two glutaminergic
synapses and they fire, it might be. Probably not.
Maybe they have to fire at the same time. Maybe if I have a hundred out
of a thousand. Imagine that I have a hundred
different glutaminergic synapses that fired simultaneously then what
will happen? I'll get positive charges at all of them.
And maybe that's enough to draw some negative charge away from the axon
and start an action potential going, or maybe not. Maybe you need two
hundred. What if they don't fire at exactly the same moment?
Well, the minute one fires it makes it locally positive,
but then it starts restoring itself so that if they're separated in time
they're not as effective as if they happen simultaneously.
So, we have an extraordinary complex analog integration
circuit here. The analogy integration circuit
depends on the temporal arrival of these signals.
And what else does it depend on? The number of the signals. So,
let's get this down. We're going to integrate the
It'll depend on their timing, the number, and the geometry,
because it turns out that doing it at different places in the,
now, I drew my dendritic tree, the dendrites as all these little
hairy spikes coming off the cell body, but the dendrites are vastly
more complex than that. Some cells have elaborate dendritic
trees. The dendritic tree,
the dendrites of some neurons, here's the cell body, can go off in
all sorts of wonderfully complex patterns. And it may be more
effective to hit synapses close to the cell body or synapses on
different parts of the tree. And so that the entire shape of
that dendritic tree can have an effect, and where you're hitting it
has an effect. So, whereas the action potential is
a very simple thing, which you might say just replace it
by a wire for our computer modeling studies, goodness,
nobody has actually succeeded in building a perfect model of the
integration properties of an dendritic arbor for a single neuron.
They can get guess and approximations.
So, there's an amazing integration that's going on here.
But it turns out that it's more complex than that because,
you see, I said that we had these, say, glutamate neurotransmitters
here that were causing positive charges to rush in.
It turns out there are other neurotransmitters that activate
other channels in the membrane. And, for example, there are some
neurotransmitters that activate, like glycine, another amino acid
activates ligand-gated chloride channels.
So, glutamate, one amino acid activates sodium
channels. Sodium rushes in. Glycine activates chloride channels.
What will chloride do? It can come in.
What will it do when it comes in? Negative. Oh, my goodness. So,
when glycine is spritz on the post-synaptic cell chloride comes in
and the cell becomes locally more negative. These are called
By contrast those that admit positive ions excitatory synapses.
Neurons can have both inhibitory and
excitatory synapses on their dendrites. So,
the postsynaptic cell will be receiving positive signals,
positive ions coming in from excitatory synapse and negative
signals, inhibitory signals with negative ions coming in.
The integration of charge in the dendritic arbor is an integration
problem of the timing, number, geometry and sign,
positive or negative, of these activation signals.
That's what's going on. And what happens is the neuron
integrates these signals, positive and negative. So,
we'll make this one a glycine neuron, negative, negative, negative.
All that integration takes place right over here in the region of the
cell called the axon hillock, which is the first place that the
action potential mechanism is found. And, of course, that integration is
nothing more and nothing less than figuring out whether the membrane
potential gets above minus 50. If it gets above minus 50 it fires.
Does the nucleus participate in the, in what way would the nucleus
It's an interesting question. I mean the nucleus does, in a sense.
The geometry of that cell body there has some effect on the
electrical properties and all that, but if you think about the
timescales. How often do neurons fire? At a frequency often of about
a millisecond. So, that means everything I've just
old you, this complex integration problem is occurring within
a millisecond. The processes in the nucleus that I
think about typically of transcription and translation and
all that are operating several orders of magnitude more slowly than
that. You know, they'll operate, even in the best of
circumstances, at seconds, and often at more than
that, minutes before you could get transcription and translation and
stuff like that going. So, the nucleus, I think,
for the most part, better get its act together by producing stuff and
getting it out to the periphery, but probably through the expression
of the genome can't do much in a relevant millisecond or so.
But I wouldn't be shocked if some neurobiologist knows better than I
do that nucleoli do something. I mean there are many cleaver
things that are going on. I'm sure a cell has wasted anything,
but with respect to the operations we've talked about probably not.
OK? But I'm always reluctant to say something never happens in any
possible way. All right. So, now how does all this get stuck
together? Well, not only do we have this
complex integration within the dendritic arbor but,
of course, the neurons are stuck together into circuits themselves.
If we had more time I would draw the circuit that you use to
integrate complex functions in calculus, but not having much time
I'm going to just go for a much simpler circuit here.
I'm just going to go back to nerves and muscles. And here we go.
Suppose I tap right here below your knee. What happens?
There's a reflex. Let's at least get that going,
OK? What happens is when I tap there above your patella,
here's your kneecap here, there's a sensory neuron.
The sensory neuron brings out a signal and it goes into the
spinal column here. This is a reflex.
It doesn't need to go up to your brain. You don't need to think a lot
about it. And it goes into the spinal column here into the dorsal
root ganglia. This is a cross-section.
The, sorry, sensory neuron comes in here. And what it does is that
sensory neuron makes a synapse, and actually another synapse, and it
makes a synapse on a motor neuron. The motor neuron comes back and
synapses on that very muscle. It is the simplest possible circuit.
I sense, I send one sensory signal up into the spinal cord,
there's an excitatory positive synapse onto a motor neuron,
this motor neuron fires and contracts my muscle so I go back.
At the same time, this guy makes another synapse,
a positive excitatory synapse on a little cell that is an interneuron,
that's an intermediate neuron. That intermediate neuron makes a synapse
on a second motor neuron, but this is an inhibitory synapse.
That motor neuron sends its process
out and is affecting the opposite muscle. So now what happens?
Let's get this straight. I hit over here.
And the signal goes back to my spinal cord. The sensory neuron
causes one motor neuron, directly by firing on it,
to contract. It causes an interneuron to fire that inhibits
the opposite motor neuron. What happens if you inhibit the
opposite motor neuron? You relax the contraction,
or you at least don't contract the opposite muscle.
So, what happens is you send a positive signal to the muscle on one
side and you inhibit the signal to the muscle on the other side.
It's a very simple circuit. It's got one sensory neuron.
Two motor neurons. One interneuron. It's got two positive excitatory
synapses. It's got one negative inhibitory synapse.
That's about it. Presumably, everything else that goes on in
daily life is basically the same thing. This is probably what eating
lunch is like, falling in love is like and things
like that, although the details remain to be worked out for exactly
how that stuff works. There is a large collection of,
I give you the simple examples because obviously we don't know a
lot of the complex examples. There is a lot more to this.
If had time in the course we could go into what's known about more
circuits. I joke. We know about the circuits that
help you see vision, that allow you to pick up signals in
your retina, transmit them back and reconstruct things with positive and
negative signals that allow you to see a straight line,
for example, and recognize a straight line.
And there are patterns of cells that send positive signals and negative
signals, and when you integrate them you can get a signal if and only if
there's a straight line at this angle in your visual field.
And people know about that kind of stuff, but some of the more complex
stuff we don't know about. There are lots and lots of
neurotransmitters, glutamate, glycine,
histamine, serotonin. ATP can be a neurotransmitter.
Adenosine can be a neurotransmitter. There are peptide neurotransmitters.
Endorphins, oxytocins and even gases. Nitrous oxide is a neurotransmitter.
And then some of the drugs you may know work by affecting these
neurotransmitters. Prozac and the general class of
selective serotonin reuptake inhibitors. Prozac effects a
specific process with a neurotransmitter.
There's a neurotransmitter serotonin. After it's fired out,
instead of acetylcholesterase being in the synapse destroying it or some
other enzyme destroying it, it's taken back up by the cells.
If you could inhibit the process by which you take up your serotonin
again, the serotonin would last longer in your synapse and you would
be happier, give or take, roughly speaking to the extent that
more serotonin is a good thing. And that's what Prozac does.
Actually, it's one of the things Prozac does. There's good evidence
now that Prozac does other things, too, including causing neuronal cell
growth, but that's a whole other story.
There are things like cocaine. Cocaine is a bad thing because it
inhibits certain sodium transporters and other things.
And if you go through all of the different psychoactive drugs they're
affecting different parts of these processes. So,
for Friday I've invited a colleague who is a real neurobiologist,
I'm not a card-carrying neurobiologist,
to talk about some of the more far out things of learning and memory.
Andy Chess who's a good friend and a colleague is going to talk about
learning and memory. And then have a good time with him,
and I'll see you subsequently.