Stanford University.
I would like to get
started, please.
So my name is Patrick House.
I am a neuroscience PhD student.
I work with Robert
in Robert's lab.
I'm a first year.
And I study something that
you guys will eventually
hear about, but I don't
want to ruin the punchline.
But today we're going to talk
about memory and plasticity.
And so two days
ago on Wednesday,
you guys all sat in
here, in this room.
And you learned, some of
you for the first time,
some of you for maybe
the 10th time, the basics
of neurobiology, of
how a neuron works,
how a neuron-- you have
a presynaptic cell,
you have a postsynaptic
cell, and this kind
of simplified version of the
communication and information
transfer.
And something
interesting happened
between now and then,
which is that now you
sit in the same room.
And something about you knows
something about neuroscience
now.
You heard one of the TAs talk.
You slept on it.
And then you come
back now and you
have assimilated, integrated
into your identity,
into what you know, new facts.
And this lecture is
about how you do that.
And to kind of get
at what memory is,
we need to think about
a lot of different ways
in which it's interesting, and
a lot of different spectrums
and severities about memory.
So why is it that some
memories last our entire lives,
whereas other memories, we
hear and they're fleeting?
They go away in a second.
Why is it that someone
sitting next to you in bed,
telling you a
story, and as you go
to sleep you can't remember it?
As you wake up, you can't
remember your dreams.
But if that exact same
person, that exact same story
was told to you as they were
sitting next to you in a car,
and you get into a
car accident, suddenly
that memory becomes salient.
You may remember it for years,
if not your entire life.
And you may actually associate
either the story itself,
the voice of the person,
with that traumatic event.
And you might get
post-traumatic stress disorder.
So if the mechanism is
the same between these two
types of memory, between ones
that are fleeting and forgetful
and ones that last your
entire life, the question is,
how does environment,
how does context
fit into shaping these
types of memories?
And so in order to
understand that,
we have to kind of get at, what
are the mechanisms of memory?
And how are these
contextually motivated?
So I want introduce to you
first Stephen Wiltshire,
who is an architect, if not
in practice, at least in mind.
He is an autistic savant.
And he has been mute
since age three.
And he has this remarkable
capacity, which I'm actually
going to test you guys on
slightly here, if you have
any kind of
inclination to sketch,
or you happen to have some
sketch paper with you.
I want you to-- this will
take approximately 60 seconds
to span across all
of Rome-- draw it
from memory in your 60 seconds.
Because Stephen Wiltshire
has this amazing capacity
to take helicopter rides--
he's done this over Tokyo.
He's done this over New York.
He's done this over
Rome and over London.
And in 20 minutes,
he can then sit down
and recreate every single
building, every single column,
every single window in
correct proportions,
from the correct angle in
which the helicopter ride was.
And so you may be thinking-- OK,
your 60 seconds are almost up.
Can you guys do it?
You may be thinking-- if any
of you are artists out there,
you may be thinking
this is unfair.
Why can't I do this?
And as neuroscientists,
our first thought
is, OK, this is unfair.
Why can't I do this?
But really, it can
tell us something
interesting about memory.
So you come at it
with two questions.
First question-- before and
after this helicopter ride,
what is different
in Stephen's brain?
And second, on this theme
of individual variation
that we keep harping on in
class, why is it that he can
do this and we can't do this?
And these are two
important questions
that if we could
answer those questions,
we would know a lot
about what memory is.
And so it really
makes sense to go back
to what it is that we
know so far about neurons,
the basics of one neuron
and how it is activated.
And so we have a
presynaptic cell,
and we have a postsynaptic cell.
And in our simplified version,
we can kind of know now--
and what I'm going to
tell you is that memory,
learning happens, to the best of
our knowledge, in the synapse,
in the space between the pre
and the postsynaptic cell.
But to understand why it is that
we think that, we kind of need
to go back about 100
years to when people,
scientists, neuroscientists
were investigating the brain,
investigating memory.
And they thought that the
smallest unit of the brain
that they knew was the neuron.
So because of our
tendency to explain
what we don't know in terms
are the smallest unit of thing
that we do know,
they thought OK,
this makes sense-- a
memory is a new neuron.
And when you learn
a new fact, when
you learn the basics
of neuroscience,
you are growing new neurons.
And each individual fact is
associated with one new neuron.
For instance, they
may have thought
that OK, you guys learned
on Wednesday that the axon
hillock is the site of the
generation of the action
potential.
So then that is a new
fact, and then a new neuron
would then be formed.
I just realized that that
actually might not make sense,
because at the time that they
thought that, they didn't know
what an axon hillock is,
so maybe that formulation
doesn't even make sense.
But the idea is that a
couple decades later, people
discovered the synapse.
They discovered that
neurons were not just
one interconnected thing,
that there is space.
There is a gap between them.
And as soon as they
discovered the synapse, that
then became the smallest
bit of information
we knew about the brain.
And then theories came out
saying, well, no, memory
must be the formation
of synapses.
So the dogma at the time was
then that OK, new fact, axon
hillock.
What does this
mean in the brain?
You can see this in the brain.
This takes the shape of a
new synapse being formed.
And what we think of now is that
well, this isn't exactly right,
because new synapses are not
being formed all the time.
And new neurons are not formed
in the adult brain, which
isn't entirely true, but
we'll get back to that.
But the idea is just that
memory and storage of learning,
what I'm going to tell you
is that it's in the synapse,
and that it involves modulation
and change of the synapse.
And why do we think that?
Because we understand
the molecules.
And we understand
at a molecular level
what's happening in a
synapse when it changes.
So that it is thus
now our smallest level
of understanding of the brain.
And so of course, we
think oh, well that's
probably where memory is.
So that's the dogma that
we're going to start with.
And we're going to
start with this idea
that memory is
synaptic plasticity.
Memory is when the
space between the
presynaptic and postsynaptic
neuron changes in some way.
And not only that, it
changes in one direction.
It gets stronger.
It's strengthened.
And so what this
means is that if you
have your presynaptic
neuron and you fire it,
and you get some
amount of response,
that over time, if you give
enough presynaptic activation
in a certain time window, that
you will then get a heightened,
strengthened response in your
postsynaptic cell eventually.
And that is the
kind of mechanism,
the overarching, broad
mechanism of LTP.
And so what we need to
do to understand memory
is to focus on the synapse.
So what we get is our
classical picture, which
is that you have your synapse.
And a neurotransmitter
is coming out.
And that neurotransmitter
is excitatory.
And in your postsynaptic
cell, what you're getting is
you're getting a small
amount of activation.
You're getting current
that comes into that cell.
You're getting ions,
some sort of response
for any individual piece
of neurotransmitter.
So what this is, is a
version, a simplified version,
of what is called
Hebbian plasticity.
And so there's this guy
Hebb, which you have to know.
There's a few of names you
have to know in neuroscience,
and he's one of them.
And Hebb came up with this
idea, the only bumper sticker
that neuroscientists ever
have on their car, which
is that neurons that fire
together wire together.
And what this is saying is that
you have your standard picture
of a very, very simplified
version of a presynaptic cell
that's releasing an
excitatory neurotransmitter,
and that when it does
so, you get a response
in your postsynaptic cell.
So if you will remember
from one lecture ago,
that excitatory
neurotransmitter is glutamate,
though if you're going
to spend any time
and energy into remembering
one neurotransmitter that
might be relevant for
the class, this is
the one you want to remember.
You don't have to remember it.
So mostly, the idea is
just that it's excitatory.
And why is this important?
Because information is
transferred in the brain
through activation.
And in order to
transfer information,
you need excitatory
neurotransmitters.
You need your neurons
to be activated.
But as we know from
what I've told you
so far, that repetition
is what drives memory,
I would suggest that you
remember that glutamate
is the excitatory, and one
and only neurotransmitter
that you have to know.
Say there's a test
question that says,
what is the one excitatory
neurotransmitter
in the brain that
you have to know?
You would respond glutamate.
And then you would be right.
And so you can imagine that
for this type of simplified
diagram, if we
were to strengthen
the synapse, if we were to
get some sort of plasticity,
some sort of change,
potentiation,
you could think of a
few ways of doing this.
You could take the
presynaptic neuron
and change how much excitatory
neurotransmitter is released.
You could change how much
glutamate is released.
And presumably, if you release
more of the little circles
with positive charge
in them, then you're
going to get more activation
in the postsynaptic cell.
Another thing you could
do is basic neurochemistry
in this diagram, is that each
of those neurotransmitters
is binding to a receptor
on the postsynaptic cell.
And so what you can do is
take that individual receptor.
And you can make it respond more
to a single, individual unit
quanta of neurotransmitter.
Alternately, you
could just increase
the number of postsynaptic
receptors on your cell.
And all of these would
be mechanisms by which
you could take this
very, very simple synapse
and potentiate it, such that
you get the same release,
you get the same
neurotransmitter.
And what you get is subtle,
because LTP is often
very subtle.
You'll just notice that the
response is slightly larger,
a slightly larger response
given the same amount of input,
given the same amount of
output of the presynaptic cell.
And this is the entire idea of
LTP, long-term potentiation,
this idea that at your
individual synapse,
you can potentiate it.
You can change it.
It is plastic.
But there should be
one large red flag
here, which is--
one of these caveats
is, well, your
presynaptic neuron,
how does it know whether or
not LTP should be undergone?
How does it know whether or
not LTP has been induced?
This requires a kind
of communication
between both the pre and
the postsynaptic cell,
that how would the presynaptic
cell, which has already
released its
neurotransmitter, know?
And what you get is this
kind of heretical type
of neurotransmitter
that can actually-- we
call it a retrograde
neurotransmitter--
that can actually be sent back
from the postsynaptic cell.
And it's a gas.
Nitric oxide is
an example of one.
It's what you get
at your dentist.
And it kind of goes
back and diffuses
back across the synapse
and actually modulates
how much neurotransmitter
gets released
from the presynaptic cell.
So we have these mechanisms.
We have these mechanisms of LTP.
And the question then is, where
does this happen in the brain?
And why is it that
we believe that these
are the places of LTP?
And one of the things
you need to know--
this is our first dive
into neuroanatomy--
is you need to know
the hippocampus.
It was introduced
to you last lecture.
But if there's one
neurotransmitter you
need to know, it's glutamate.
And if there's one neural
anatomical structure
you need to know at this
point, it's the hippocampus.
I'm kind of always jealous of
these autistic savants that
can memorize 10,000 digits of
pi, and take a helicopter ride
and then fully recreate the
cityscape of any city they see.
And if you read interviews
about how they do it,
it's really interesting.
So what they seem to
do is not memorize
just a sheet of a bunch of
digits, a string of 10,000
digits of pi.
They'll take a walk through
their childhood town.
And they'll say that they
put one of the digits
on each and every object.
So your mailbox will
be the first digit,
and then your neighbor's
door will be another,
and then their
window will be three.
And then they are
not re-conceiving
and reconstructing just a
sheet of boring numbers.
They're taking spatial
tours through their memory.
And what this always
compels me to do
is make these kind
of visual mnemonics.
So I'm going to give you a
visual mnemonic for the one way
you have to remember
that the hippocampus is
the site of memory
and the site of LTP,
insofar as this class is
concerned, which is-- OK,
hippo horse.
We learned that last time, it
looks kind of like a seahorse.
But that doesn't
really make sense.
What if you think about this?
What if you think about the
hippodrome back in Rome?
Hippodrome is the
circular arena where
you had your little chariot
races, because of horses.
And there's two
different scenarios
that I want you to imagine.
The first is-- you guys remember
Michael Jordan and Larry Bird?
They had this commercial
where they played Horse.
And what they were doing
is they were playing-- you
have to make a basketball shot.
And then the next one,
you have to remember
what that first
person did exactly,
and you have to recreate it.
So what I like to imagine is
Larry Bird and Michael Jordan
playing a game of horse in
the hippodrome, back in Rome.
And then you can kind of
get this idea of how memory
is related to the hippocampus.
and this horse structure.
And if that doesn't
work for you,
I have one more,
which is actually
my favorite, which
is you can imagine
the entire amphitheatre,
the entire hippodrome filled
with people.
And there was that one emperor
who named his horse a senator.
Do you guys know who that is?
What's his name.
I don't know his name.
Caligula.
Caligula, there you go.
So imagine the entire hippodrome
is filled with people.
And Caligula is there.
And he gets his senator horse
in the middle of the field.
And the horse is sitting
kind of cross-legged.
And he's typing out your
memoirs on a typewriter.
And that is how you're
going to remember
that the hippocampus, the
hippodrome, the horse,
is where memory is formed.
So now you guys are all
autistic savants now.
Really though, what
we need to determine
is, why is it that
we really think
that the hippocampus is the site
of LTP and memory formation?
It turns out that there is
actually adult neurogenesis
and adult plasticity.
So in the last 10
years, we've discovered
that the adult brain really
does actually form new neurons.
And for the last 100 years,
we kind of disregarded that
and said those guys
who initially believed
that every new neuron is
associated with every new fact,
those guys were just totally
wrong and ridiculous.
What a ridiculous concept.
And so perhaps
eventually, in the future,
we will have to
incorporate this idea
that there does seem to be
some neurogenesis in the brain.
But much like how we
learned that there
is non-genetic inherited
traits, which we had learned
from the disreputable Lamarck,
way back in Lamarckian
evolution, that there
is no-- for 100 years,
we thought, no, it's impossible.
There is no non-genetic
inheritance of traits.
But it turns out
that, well, OK, we
do seem to have some kind
of non-genetic inheritance.
And so Lamarck isn't
entirely wrong.
And it turns out this is a
kind of similar thing, where
the people of most disrepute are
often just a little bit right.
So probably, people
that used to think
that adult neurogenesis has
something to do with memory
are probably a little bit right.
But we're going to stick
with the canon, which
is that LTP happens,
and that it happens not
on the level of the neuron, not
on the level of the synapse,
but on the level of the
plasticity of the synapse.
And so why do we think
it's the hippocampus?
We get at it from a few ways.
The first way is that HM, this
kind of well-dressed epileptic
who had his hippocampi removed.
And what happened was
he had selective removal
of just his hippocampi.
And he could no longer
remember anything at all.
He could not form new
memories whatsoever.
So with these types
of conclusions,
in addition to evidence
that if you watch and record
from neurons in the hippocampus
as you're giving someone
a learning task,
then you see LTP.
If you pharmacologically
block LTP,
you see changes in
the hippocampus.
And so all these
pieces of evidence
are trying to get at the
idea that the hippocampus is
necessary for memory and
memory consolidation.
But if you introspect
a little bit,
you can probably
realize that well, we
undergo all kinds of forms
of learning and memory.
We have motor learning.
We learn how to shoot baskets.
We learn how to throw darts.
We understand
emotionally that events
that are more emotionally
salient are more memorable.
And so how is it that
these types of things
are also encoded
in our brain, also
encoded in the same region, the
one region, the hippocampus?
And what that turns out
to be is that, well, it's
not just that one region.
LTP is happening
all over the brain,
that if you look in your
emotional regulation centers,
if you look in your emotional
cortices, you also see LTP.
And this makes sense, because
these types of memories
have to have different methods
of storage and retrieval.
And also, that you can imagine
this type of excitation,
this type of synaptic
plasticity, can go wrong.
In post-traumatic
stress disorder,
for instance, you get LTP.
And you get LTP that is severe.
And you get severe LTP
potentiation of your synapses
in those emotion
regulation centers that
create a situation where the
context leads to memories that
shouldn't necessarily
be brought up,
that shouldn't
necessarily be retrieved.
And so we see this mechanism for
types of behavior that we know,
types of things like
why certain memories,
certain emotionally salient
memories last for a long time,
and others don't.
And we can also
imagine that this
is a physiological
process, and that it
can go wrong, occasionally.
We all know that
memories are degraded,
sometimes intentionally so,
sometimes unintentionally so,
that there are certain
things we want to remember.
And despite any and all
repetition about glutamate
being the excitatory
transmitter,
we just don't remember them.
And there are some that just
kind of fade away into time,
into the oceans.
And what is happening
is that there
are mechanisms for
intentional disruption of LTP.
And you can think of a few.
So hypoglycemic states, if
you are really, really hungry,
you get insulin cascades
that end up reducing LTP.
If you're starving,
it's not a good time
to try to remember things.
It's a good time
to try to go out
and expend energy finding food.
As we'll learn
later in lectures,
there are some stress hormones.
And these stress
hormones actually
give us a selective memory
advantage in the short term.
If you're in a car crash,
you remember the slow motion
details of the entire event.
And this has to do with
these stress hormones,
these fear hormones
coming out and saying,
OK, well, we want to be
able to remember this moment
so we can learn from it
next time, if we survive.
But if you do this chronically,
if you do this for a long time
window throughout the
lifetime of the organism,
then you can actually get damage
to LTP and damage to memory.
So it's about time window.
It's about the same
mechanisms that
can enhance memory can also
be deleterious eventually.
Another probably
more familiar one,
perhaps not to the
introverts, but perhaps
to the extroverts
in the crowd, is
that if this lecture
were on Saturday morning,
I could probably ask you
guys what you did last night.
And some of you would
not be able to tell me
with delicate accuracy
what happened on Friday.
And you might not be
able to tell me the story
that was read to you
at bedtime, or even
who read you the
story at bedtime.
And this is because ethanol,
alcohol, directly disrupts LTP.
And we see this.
And we see this in
the hippocampus.
And these are the types
of things, behaviors,
that we know of.
We know that emotionally
salient memories last longer.
We know that alcohol
somewhat-- there
are differential effects of
types of substances on memory.
We know that it's hard
to remember things right
before we go to sleep.
And so what's
interesting is, can we
get at a physiology that
explains all of these things?
And so I'm going to give you
60 more seconds-- there's
going to be a pop
quiz at the end,
by the way-- you have 60
more seconds to do this.
And what is interesting here
is that when we get down
to these physiological
mechanisms,
we have two ends of a spectrum.
We have HM and we have
Stephen Wiltshire,
someone who cannot form
any memories whatsoever,
and then someone who can do this
in a 20-minute helicopter ride,
recreate the entire landscape.
And the question is,
the theme of this class
is often one of
individual variation.
How is it that
one person can not
be able to form any
memories whatsoever?
How is it that one
person can have
an autistic,
photographic memory?
And where do we fit?
Where does memory fit in a
properly functioning way?
And like most of
the spectrums that
are introduced into
this class, one
of imprinted genes, tournament
versus pair-bonding species,
things like that, the
answer turns out to be we
are somewhere in the
middle between HM,
no hippocampi, no
formation of new memories,
and Stephen Wiltshire.
So one more thing
we need to discuss
with the theme of this
class is that often, we'll
give you a lecture and then
maybe in the next lecture,
maybe five minutes later,
we'll tell you it's all wrong.
Or we'll say, no, you've
been way too myopic.
That's not how you
should see these things.
And what we need to do in
order to understand somewhat
about the context of memories
is to take and expand
your myopic view of this
simplified version of a neuron.
So far, we've gone into
what a single neuron
functioning looks like.
And we've gone into what a
single neuron as it transmits
a signal to another
neuron looks like,
how there's a gap in between the
pre and the postsynaptic cell,
and what that information
transfer looks like,
and how we can change that
information transfer, how
we can make it plastic.
But there's a
problem here, which
is that if we're trying to
learn anything about the brain,
we have to understand that the
brain is really complicated,
and that there's
100 billion neurons,
and that sometimes these
individual neurons will connect
to 10,000 other neurons.
And sometimes, each of
those 10,000 neurons
will have 10,000 neurons
that connected to it.
And so the question--
I don't know.
As a neuroscientist, when I look
at that, the first thing I do
is want to give up.
And I do.
And then the second
thought is OK, maybe
it's time to expand
the simplified version
of the neuron that we have.
It's not just one neuron
talking to another neuron.
It's not just a single
synapse, but that it's
the dynamics of many,
many interacting neurons.
And as these dynamics
expand, as these dynamics
get introduced into 10,000
neurons at the same time,
10,000 dendrites,
dendritic arbors
connecting to 10,000
other axonal processes,
then we see that things
that didn't matter
so much in the single,
individual neuron actually
matter quite a bit
when you're talking
about 100 billion neurons.
So one of the things
to introduce here
is the concept of noise into
the individual signal transfer,
into the individual
information transfer.
A neuron, as we
presented it, was
something that fires
an action potential,
transmits information.
Every single action
potential leads
to neurotransmitter
release, which
leads to postsynaptic response.
But these are very
delicate things.
An individual
neuron is constantly
in flux with how much
current is coming in and out.
Ions are flowing around.
It's not as simple as
a static neuron that
then gets activated,
and then passes on
a message to another
static neuron, which
then gets activated.
What you get is
often, a lot of times,
you'll get random and
spontaneous generation
of signal, of action potentials,
and sometimes of current
in the postsynaptic cell.
And one of the major
tasks of the brain
is figuring out
what is signal, what
is appropriate and meaningful
signal, versus what
is this noise.
If you can imagine on
a single neural level,
the noise might not
have that much impact.
But if you're talking
about 100 billion neurons,
you're going to get noise all
over the place that will just
lead to this static of noise
that you don't know what
to make of the world anymore.
You don't know what
to make of the signal.
You don't know what to make
of individual neural signals.
And so what we need to do is
to start considering neurons
in terms of how they interact
in dynamics of groups.
And one of the first ways
and the most important ways
to think about this
is to understand
that neurons are not just
excitatory forces, that
information, yes, is
generated by glutamate
and the transfer of
excitation, but that neurons
have a capability to inhibit.
And one of the important ways
that they differentiate signal
from noise, one of the important
ways to learn what is noise
and what is not, is to inhibit.
And I'll explain
how it is exactly
that the inhibition works.
But one of the first--
oh, that's pretty high.
One of the first
ones to understand
is that a neuron can inhibit
itself, which is not really--
it seems like it could initially
be some sort of masochism,
but it's really not.
It's just that the neuron
is trying to sharpen
the signal that it's sending.
So a neuron is firing
and firing, over and over
and over, and what
it wants to say,
what it wants to be able
to do, is accurately give
a precise description of the
signal, of the information.
And what it can do is inhibit
itself to say, I'm done.
No more spontaneous noise.
No more spontaneous
little bits of current.
I am done with my signal.
And what this is, is it allows
for temporal sharpening.
It allows for the ability
of a neuron to say,
this was my signal.
It was meaningful.
I really meant it,
and inhibit the kinds
of random noise and spontaneous
things that could happen.
Another type of
inhibition that's
very important to separate
noise from not noise
is spatial inhibition.
So what this is, is
your individual neuron,
not only can it send
processes and inhibit itself,
it can actually send processes
out and inhibit its neighbors.
And how might this be useful and
important is that it can say,
essentially, OK,
this signal is real.
This signal is the
signal that I want
to send, the information
that I want to transfer.
And not only that,
ignore my neighbors.
It's really me.
And what this allows you to
do is get spatial sharpening.
So what this allows you to do
is say, in the field of things
that you're trying to
perceive, a certain neuron
will respond to a certain
section of that field.
And what this is saying
is, I am activated.
And you inhibit
your neighbors so
that you're more sure
that your signal is true.
And how can we relate this?
How can we make sense of this?
There's a very simple
type of feedback network
that should elaborate
this idea, which
is pain and pain sensation.
And so we all probably, at
some point in our lives,
presumably, have
discovered and felt pain.
And there's two general
qualities of pain.
You can have really,
really fast, sharp pain.
And you can have this dull,
aching, throbbing pain.
And what people found
when they investigate
into your spinal cord and
into your sensory peripheral
processes is how this
pain is generated.
And it's generated on two
separate types of neurons.
And one carries fast pain, one
carries the sharp, fast stuff.
One carries the
slow, dull stuff.
And what you find is that
these are intertwined
in this delicate
feedback loop, such
that the fast, spiking,
first pain will generate,
eventually, the
slow-moving pain.
It will fire the other neurons
next to it, the neighbors,
and say, OK, also start
this slow pain spike.
But then the slow pain
spike can come back
and inhibit the first sharp
spike, such that it stops.
We're trying to get
information about the world.
And your body is
trying to do what
it can with that information.
And if you get
stung by something,
you want really sharp
pain to be like,
hey, pay attention to that.
Make sure it's not a
scorpion that's still there.
But you don't need this
sharp pain forever.
You want to be able to inhibit
it and just say, OK, pay
attention.
But then, just to make
sure you don't walk on it
anymore and get
it infected, we're
going to make it
hurt a little bit.
And so this is your body
trying to make the most
of this type of information.
And what it's doing is
using lateral inhibition
in this complicated way,
actually simple way,
to allow for these two types of
transmissions of information.
That was a very simple example.
And I think there's a much
more complex example when
we go into the types of
complex visual stimuli
that vision gives us.
And you can imagine that lateral
inhibition, the same type
of spatial sharpening
of a signal,
can come into play as we're
trying to figure out and piece
together the visual world.
So what this is doing, what
this kind of lateral inhibition
allows for, is it allows for
visual neurons to receive input
and then to say, it is me.
This is the signal
that I want to send.
Not only that,
inhibit the neighbors.
And what this leads to
is this emergent property
of these retinal
cells that allow
for specific types
of signal and allow
for specific types
of receptive fields.
So in your eyes, your neurons
in the back of your eyes,
if you just stand
still, they only
have a certain angle of
light that they can get.
And that idea is this
idea of receptive fields,
that they are responsible
for that field.
And they're
responsible for saying,
if there's a signal
there, this is what it is.
And this is how it's relevant.
And what this type of lateral
inhibition allows you to do
is it allows you to say, OK.
Your neuron gets
a signal, and it
wants to say, OK,
that's an edge, an edge
detection, contrast detection.
If you look around at
the objects in the room,
often you define
them by their edges.
So we have this elaborated
neural mechanism
involving inhibition
and excitation
that allows for this type
of contrast enhancement.
And what can we do
with this even more?
So these guys Hubel
and Wiesel decided
that they were going to look--
OK, another brief anecdote.
So there's this commercial
when I was young.
And it was Michelin Tires.
And if any of you guys ever
become marketing people,
which there's enough of you that
statistically, someone will.
I don't know why you
don't make commercials
that are scary, because this
commercial frightened me.
And I was, like, six.
And I remember it to this day.
So why not, if you want someone
to remember your product,
just make it-- take
what you know from this,
and use it to manipulate people.
That's what education is.
And so I remember
this commercial.
And I just remember it
was for Michelin Tires.
And their whole point was
that no matter how fancy
your car is, no matter how
much you spend on your car,
there's only four
points of contact
between you and the road.
And it's on your tires.
And I don't know why, but this
blew my mind, and it scared me.
And it made me recognize
that, yeah, you
should get good tires.
So Hubel and Wiesel, they took
essentially the same logic,
which is that we have this
complicated visual world,
and we know that we put
it together somehow,
but our only access
to this information
is through the retina.
We have the light is the road.
These are our two tires.
We only have two tires
to connect with the road.
And so their logic
was that if we
look at each individual
neuron in the retina
and trace it back, we should
be able to see, somehow,
how this visual
world is constructed,
how it is that we go from the
only signal, the only signal
from the outside
world we get, to
this complicated visual field.
And what they found
was that if you
look at the neurons in
the back of a retina,
and then look at where
they synapse, back
in your visual
cortex, they found
a one-to-one correspondence,
that if you activate
a certain neuron in
your retina, you'll
get a spatiotopic-- which
means they're oriented
in the same way,
and all the neurons
are aligned in a
similar way-- field
in the back of your
visual cortex, in V1.
And so what that
essentially means
is that your eyes are smushed
to the back your head.
There's no information that
necessarily gets enhanced
or reduced between your
retina and the back
of your visual field.
And they're like, OK, great.
And so these guys, Hubel and
Wiesel, won the Nobel Prize.
If you could win more
than one, they probably
would have won four by now.
They were these Harvard
neuroscientist back in the day.
And they are pretty much
who you need to know.
You need to know Hebb.
You need to
understand glutamate.
You need to understand LTP.
And Hubel and Wiesel, if you're
going to be a neuroscientist,
be interested in the
brain, they will come up.
And if you're a
neuroscientist, you
have to invite them
to your wedding.
You have to do everything.
I don't even know if they're--
they might even be dead.
You have to seance
them, or something.
But what they decided to do
was then, OK, now we're at V1.
We're at the one level
of visual cortex.
What else can we do?
Where does the scene get
constructed that we see?
And what they did was
looked one layer up.
And they did the
exact same thing.
They fired individual
retinal neurons.
And they looked in
the next layer up.
And absolutely nothing happened.
There was no activity anywhere,
no matter what they did.
It fired all of them, and
there was no activity.
And they were like, oh, damn it.
We're not going to get
invited to any weddings.
What are we going to do?
But what they discovered
was that if you activated
enough retinal
neurons, and that they
were in a certain spatial
orientation, say a line,
then you get activation
in this other layer
of your visual cortex.
And what they discovered,
and what was on, I'm sure,
the construction of all of
their wedding invitations,
was that if you have
certain neurons that
are selective to certain
orientations of lines, like so,
if you imagine these
are four neurons,
a single neuron will be
responsive to a vertical line.
A single neuron, another
one, a different one,
will be responsive
to a 45-degree angle,
a horizontal line, 135 degrees.
And so what you get, and you're
starting to piece together,
is this way of constructing the
visual world that is layered,
and that extracts out features,
and that through those features
you get individual
neural activation.
And you might imagine that
if you go up even further,
you would get some sort
of more higher order
types of activation,
individual activation,
in your visual cortex, something
like, say, a neuron that only
responds to an orange, or
a neuron that only responds
to a banana, or a
neuron that-- so this
is one of the terms
in the field--
only responds to
your grandmother.
And they call it a
grandmother neuron.
And there's this kind
of El Dorado type
quest for grandmother neuron.
Where can we find it?
And the problem is,
nobody ever found it.
So then the question
becomes, again,
related to memory, related
to even our understanding
of these kind of
networks of neurons.
Where are these memories stored?
This is slightly out of order.
But basically, this is
an example of, again,
your lateral inhibition.
So to understand how it is that
these signals are sharpened,
this is a nice visual illusion.
Do you guys see little dots
of dark between each of those?
That is an artifact.
That is an artifact of
your visual perception.
That is an artifact of
you constructing that.
And why is that happening?
Because at each of those
individual corners,
you're getting the
most amount, because
of the four axial bars of
white, of lateral inhibition.
So in every single one
of your brains right now,
whenever you look at
the individual corner,
you're getting
lateral inhibition.
And so you can imagine
that this type of thing
is a demonstration of
lateral inhibition.
Another type of thing, when
I was talking about pain,
there's this fascinating
thing where-- we all
know this-- where if
something itches, say,
you have a mosquito bite.
And you want to scratch
the hell out of it,
because sometimes it
feels really good.
You notice also that you
can scratch around it.
You can make hard,
kind of painful stimuli
in the immediate
vicinity, and just
do it really,
really hard enough.
And you get lessening of pain.
And what that is, is
the same type of thing.
It's lateral inhibition of the
focal point of the mosquito
bite.
And so these things
sound abstract,
but these things
really are real.
And we can see them,
and we can feel them,
if we know where to look.
So one last idea.
We're trying to
get at, OK, where
are these memories stored?
Where are these facts?
Where is what you know now
about neurobiology stored?
And it's helpful to introduce
the idea of neural networks.
There's 100 billion
neurons in the brain.
These are not
communicating one to one.
These are communicating
with tens of thousands
of other types of neurons.
And if you simplify this
down to just the basic idea
of a neural network,
such that you
have your bottom,
first layer cells.
And these first layer cells
respond to, respectively, left
to right, Monet, Cezanne, Degas.
They just respond.
For some reason,
they have been tuned.
They have undergone LTP.
That is what they respond to
in this very one-to-one Hubel
and Wiesel kind of way.
But what we notice is that
there's this elaborate property
you get when you start
to combine neurons
with many, many other
types of neurons, which
is that you get a network.
And you get a network without
one-to-one correspondence.
So if you look at the top
row, and you get neurons A
through E, A still responds
in this one-to-one way,
with just Monet.
E, again, you got just Degas.
So those are not really
informative in the way
in which we want to understand
the emergent property,
and what's important
about neural networks.
What we get out
of neural networks
is emphasized when
we focus on C. Neuron
C doesn't know-- if it gets
activated, what can you tell?
You don't know which
input it came from.
You don't know whether it came
from the first-layer neuron
1, first-layer neuron 2, or 3.
You don't know whether or not it
was a Monet, Cezanne, or Degas.
All you know is that
it's one of those three.
And what you get
now is this idea
that you can have concepts,
and you can have categories.
And you can have a
category of impressionism.
That doesn't
necessarily give you
information about individual
types or names, or which
neuron it came from.
But you have a
network of neurons
with different concepts in it.
And amidst this
network, you can now
understand how it is that
environment and context can
impinge on the storage
and retrieval of facts.
So the idea that emotionally
salient memories are longer
lived in your brain, in your
synapses, in your plasticity,
than other ones,
well, how is that true
if they're not contextually
related, if the mechanism is
the same everywhere?
But what you begin to see is
that if you combine context
in this version of
neural networks,
you start to get the neural
representation of context,
the neural representation
of environment.
And this makes sense
if you think about how
we try to remember things.
If you try to
remember something,
and you know it's an
impressionist painter,
or you know it's
within a category,
but you're not quite
there, you kind of
take a tour of categorical
ways of thinking
and categorical learning
and categorical objects
in the world to try to
get at how that one fact,
that one bit of information
that you're trying to remember.
So it's not that individual
memories are stored in neurons.
It's not that they're stored
in the generation of synapses.
It's not that they are stored
in entirely just the plasticity
of single synapses.
It seems that we can
get at and explain
a lot of these types of
memory by understanding
that memory is one
aspect of the formation
of these neural networks,
and that if we have
100 billion neurons,
we can imagine
elaborate and complex ways
of designing these things.
So here we go, one more time.
Many very different
things happen
when we remember,
everything down
from the synaptic
plasticity all the way up
to this impressionism,
categorical way of thinking
and remembering about things.
And what is again
interesting here
is that you can
imagine-- what we've
learned about polymorphisms,
genetic individuality
and variation, that
certain people can have
different stress responses.
The person next to you can
have a different response
to stress than the other person.
One person will be more
afraid of public speaking
than the other person.
One person will
respond a certain way
based on prenatal,
postnatal environment,
all these different things,
all these different variations,
these polymorphisms that lead to
individual and varied behavior.
And now we can understand that
a polymorphism in how much
presynaptic glutamate
gets released-- remember,
glutamate, excitatory--
a polymorphism
in how strongly your
postsynaptic receptor responds,
a polymorphism in the ways in
which your neural networks are
constructed, these types
of individual things,
which each are their own
variable in your brain's
construct of memory, can lead
to different and individual ways
in which we remember.
Some people are just better
at remembering than others.
And what we're trying to get
at is from the spectrum of HM,
who can't remember anything,
to Stephen Wiltshire, who
can remember this, and where
the genetics and the environment
impact our individual memory.
And I think that's it.
So we'll take a
five minute break.
[APPLAUSE]
I'm going to talk to you guys
about the autonomic nervous
system.
So basically, autonomic
sounds like automatic.
This is anything that's
going to happen automatically
in your body, not quite
the hippocampus, horse,
like hippodrome-- like
automatic, autonomic.
So basically, your heart
beating, digesting,
goosebumps, orgasm, things that
you don't have control over--
[LAUGHTER]
Good stuff, right?
This is going to be your
autonomic nervous system.
So first, the nervous
system, remember,
is split up into the
central and the peripheral.
So our central nervous system is
our brain and our spinal cord.
And our peripheral
nervous system
is everything else
on the periphery.
And then within that, the
peripheral nervous system
can be split up into the
somatic nervous system
and the autonomic.
So we're going
over the autonomic.
Remember that.
But just to tell you
about the somatic,
that's basically the
voluntary nervous system.
So if you want to pick
up a pen off the ground,
your brain says, OK, I
want to pick up a pen.
Send the message to my muscle.
Muscle's going to
pick up the pan.
It's also your
sensory info, so when
you touch something or
smell something, information
from the periphery going to
your central nervous system.
And autonomic
nervous system, what
we're going to talk
about today, can
be split up into the
parasympathetic and sympathetic
nervous systems.
We'll go over all
those in detail.
But for right now,
one last comparison
of the voluntary and autonomic.
So the voluntary nervous
system, remember, voluntary,
moves muscles.
Autonomic, it's involuntary,
moving organs, your heart,
your digestive
system, your lungs.
The voluntary nervous
system's actually myelinated.
So what that means is there's
a myelin sheath covering
the axon, as you can see there.
And the action
potential actually
can speed up and go
down the axon faster.
And the autonomic nervous
system's actually unmyelinated.
These are just fun facts.
So it goes a little bit slower.
The good stuff, autonomic
nervous system--
so we have sympathetic
and parasympathetic.
And sympathetic is
that nervous system
where you hear fight or flight.
So anything exciting,
arousal, alertness, emergency,
like if you have a
hippo chasing after you
or something, definitely
sympathetic nervous system.
If you like somebody and are
talking to them first time,
sympathetic nervous system
activation, you're excited.
Parasympathetic is more of
the calm, vegetative function.
So after you have a huge meal,
or when you want to take a nap,
anything like that, growth,
repair, total relaxation state.
And as you can see,
they kind of sound
like they have opposing
functions, because they do.
And they tend to
work in opposition,
so it's kind of like
putting your foot on the gas
and the brake at the same time.
You can't really do that,
because they're opposing.
When the parasympathetic
system is on,
your sympathetic nervous system
is usually off, and vice versa.
So they work together to keep
our body going automatically.
OK, sympathetic nervous
system-- so remember,
this is like that huge animal,
whatever your favorite one is,
chasing after you.
What do you do?
Well, your heart speeds up.
It's going to beat faster.
You're going to breathe more.
You're going to vasoconstrict.
So what that means is you're
sending the blood-- you're
basically constricting
your blood vessels
and sending blood more to your
lungs and to your muscles,
so you can run away.
You're going to
inhibit digestion.
When you're running
away from a hippo,
you don't care about digesting
the sandwich you just had.
You're going to sweat.
Your muscles will
tense, anything
you would think of when you're
just totally freaked out.
And the parasympathetic
nervous system-- I
really like these pictures.
I found the dog, and
I got super excited.
And then I found him,
and I wanted to name him,
but I haven't thought of it yet.
But basically, they're
resting and digesting.
They're just taking it
easy, like growth, repair.
Basically anything you would
do when you're not stressed,
you have time to do now.
Your immune system
can function well.
You can spend time
digesting and urinating.
Sympathetic nervous
system-- So we're
going to look into the
neurotransmitters involved
in both the symptoms now.
So neurons-- what's
being communicated?
And I know that Pat told
you glutamate's the best.
But I'm going to fight that and
tell you that norepinephrine
is one of the good ones, too.
So basically, you
release norepinephrine
in the target organs
when you're dealing
with the sympathetic
nervous system.
So the hippo coming
at you, what you do
is you're going to
release norepinephrine,
NE, onto the target organs.
And you can see the
organs on the right.
It affects all of those.
So it's going to your heart.
It's going to your lungs.
It's going to your
kidney, your bladder.
And it's telling it-- when
it receives norepinephrine,
those organs know, OK, my
sympathetic nervous system
is activated.
I'm going to fight or flight.
I'm going to run away right now.
Or I'm going to start-- my
heart's going to beat faster.
And the one exception is the
sympathetic nervous system
actually releases
epinephrine in the adrenal.
And this is just
a cool exception.
Epinephrine, remember it's one
step away from norepinephrine
in the biosynthetic pathway.
So you can make epinephrine
from norepinephrine,
so they're not really
that different.
And epinephrine's also
called adrenaline-- adrenal,
adrenaline, see the resemblance.
And this is just
another diagram, again,
showing you norepinephrine
released on the target organ.
So you think of sympathetic,
you think of norepinephrine.
And you can see how it will
go and accelerate the heart
beat, stuff like that.
And just more in
detail, if you've
taken bio core-- I don't know
about [INAUDIBLE] bio core,
but definitely bio core-- you
know that it's not that simple.
You don't need to
worry about this.
But there's actually
an intermediate step,
where the spinal cord
projections actually
first go to this ganglion, which
then goes to the target organ
and releases NE there.
But don't worry about that.
Just know norepinephrine,
sympathetic.
Parasympathetic
nervous system-- so we
have another cool
neurotransmitter
besides glutamate and NE,
which is acetylcholine, or ACh.
And the parasympathetic, you see
it goes to all the same organs.
But now, when it releases
ACh, those organs
know parasympathetic,
rest and digest.
I have time to finish my
meal and do everything that I
can do when I want to relax.
And again, there is
an intermediate step,
where you release acetylcholine
first in the target organ.
And then a second neuron goes,
releases acetylcholine again.
This [INAUDIBLE]
Ach, parasympathetic.
And if you want more
details about it,
too, this slide is
totally extra details.
But you can see the projections
from the spinal cord
actually lead from
different places
in the parasympathetic and the
sympathetic nervous system.
And you can just see at
the end, acetylcholine
and norepinephrine
being released.
So this is a really
important slide.
That's why I put stars on it.
[LAUGHTER]
Even Sapolsky, when
he saw my PowerPoint,
he was like, spend a lot
of time on that slide.
So I'm going to.
So we're going to look at
exactly what happens when
your parasympathetic or
sympathetic nervous systems
are activated, and compare
them in different organs.
So the easiest one to start with
is your cardiovascular system,
so your heart.
You're running
away, you're scared,
or you're meeting someone
new for the first time
that you really like.
And your sympathetic
nervous system turns on.
Your heart's going
to beat faster.
Remember that.
So your heart actually
has a myogenic rhythm,
which means it actually
has a muscle that
is controlling its beating.
But what the brain does, and the
sympathetic and parasympathetic
nervous system does,
is it can change
how fast the heart beats.
So your heart's beating faster.
Your blood pressure
will increase
when your sympathetic
nervous system is on.
You're going to
vasoconstrict, remember, send
the blood to your muscles,
so you can run away and all
that good stuff.
And parasympathetic-- opposite.
Slower heart beat,
vasodilation of the vessels.
Blood's now going to the
GI tract for digestion,
and everything like that.
Another fun example is
the GI tract itself,
so your gut, your stomach,
your small intestine.
So basically, parasympathetic
activity, when you're resting,
you have time to digest.
So what you do is you
stimulate the secretion
of the acids and enzymes
needed for digestion.
You move your small
intestine with a contraction
called peristalsis.
And basically, you can go to
the bathroom, and everything
that you would do
while you're relaxing.
Sorry.
So in the heart
and the GI tract,
you can pretty much see that
they're working in opposition.
So when the heart beats
up with sympathetic,
it slows down with
parasympathetic.
GI, the opposite case,
parasympathetic turns it on,
speeds up digestion.
Parasympathetic turns it off.
I'm sorry.
This is the important slide.
So one place where they
actually do work together
instead of actually
opposing each other
is in the male
reproductive system.
And they work together for
you to erect and ejaculate.
So what happens is in
order to have an erection,
you have to be stress free.
You can't be worrying
about your test.
So which one do you think
is in charge of erection,
parasympathetic or sympathetic?
Parasympathetic.
Perfect.
So parasympathetic activation,
you get an erection.
Now let's say you
have an erection.
And now you're with
somebody, maybe.
I don't know what you're doing.
[LAUGHTER]
Whatever's happening-- sorry.
All of a sudden, you feel
your heart beating faster.
You start sweating a little bit.
Your sympathetic nervous system
is turned on a little bit now.
So now we have parasympathetic,
we still have our erection.
But we also have some
sympathetic activity,
and then more and more
sympathetic activity.
And all of a sudden, sympathetic
activity completely takes over.
And what happens?
You ejaculate, right?
So parasympathetic-- erection,
sympathetic-- ejaculation.
And it's actually a cool fact
about erectile dysfunction
that about 60% of the cases are
due to stress and not actually
organic basis in your body.
So if you're stressed
out all of the time,
your parasympathetic
activity won't turn on,
so you can't have an erection.
And also, we can explain
premature ejaculation,
if you want to to
your friends tonight.
You can just be like,
well, let's think about it.
So I have an erection, but I'm
going to ejaculate too soon.
So parasympathetic transition
to sympathetic transition,
or the parasympathetic
transition to sympathetic,
happens too quickly, your
premature ejaculation.
[LAUGHTER]
And then health,
so immune system.
[LAUGHTER]
When your parasympathetic
system is on,
you can take care of
your immune system.
You have the time to make
the white blood cells.
But when you're chasing away
from a predator or an elephant,
you really don't care about
making new white blood cells.
And this could also explain
why it's easier to get sick
when you're stressed out.
Your sympathetic
is too much caring
about your stressful
situation than taking
care of your immune system.
I don't know-- oh my
computer goes on sleep.
I think that's it.
So again, we see there's
a balance between the two
branches.
So sympathetic, you're
running away from a snake.
When that's on,
parasympathetic's
off, and vice versa.
And there's actually a really
cute video that I found.
And you have to click it twice.
So the sympathetic
nervous system, this video
will tell you everything
that I just told you.
It increases heart
rate, makes your pupils
dilate so you can see further,
run away from the predator.
You don't have time to digest.
You don't care about nasal
secretions right now.
[LAUGHTER]
You're not going
to produce saliva.
Who cares about eating?
Inhibits the liver,
kidneys, and gall bladder,
and stimulates sweating.
We're going to sweat when we're
running away, getting scared.
Causes piloerection,
so when your hair
stands when you're nervous.
Makes the lungs dilate,
you can breathe faster.
Increases muscle strength
so you can run away,
and is important for orgasm.
[LAUGHTER]
Sorry.
Parasympathetic, opposite, so it
makes your heart rate go down.
Pupils are going to contract.
You're going to digest.
You're going to like the
nasal secretions now.
[LAUGHTER]
You're going to stimulate
the liver, the bladder,
and the kidneys.
You constrict your lungs.
You're going to pay more
attention to your digestion.
And it's important for sexual
arousal, remember erections.
You can play it again later.
So an important
point to make is when
we think about sympathetic
nervous system,
we're thinking about arousal,
emergency, fight or flight.
But that doesn't mean it
always goes to the organ
and excites it.
So in the heart,
when norepinephrine
goes from the sympathetic
nervous system to the heart,
it does excite the heart
and make it beat faster.
But when it goes
to the GI tract,
it inhibits GI tract activity.
So it's not always excitatory,
it's not always inhibitory.
It depends on the organ.
Same with parasympathetic.
We think of it as being
the slower moving one.
But in the GI tract,
it does excite it.
In the heart, it inhibits.
So what does that mean?
It means we need two different
receptors on our organs
that respond to norepinephrine
or acetylcholine.
So on the heart, for instance,
for norepinephrine, you'll
have an excitatory
norepinephrine receptor,
because it will get excited
and make the heart beat faster.
But in the GI tract, you'll have
an inhibitory norepinephrine
receptor that will respond to
the sympathetic nervous system
and slow it down.
And then for the
parasympathetic,
you'd have an excitatory ACh
receptor on your GI tract
to speed it up, to
digest more food.
And you'll have an
inhibitory ACh receptor
on the heart to slow it down.
So just see you
can't always have
the same receptor
on the same organ,
or else it wouldn't
respond right.
And this is just
showing you, again.
So the heart there, you have
your inhibitory ACh receptor,
which tells your
heart to slow down.
Excitatory norepinephrine,
heart speeds up.
And in the GI tract, if
ACh is coming your way,
it will attach to the
excitatory receptor,
and it'll be like, digest.
And you have the inhibitory
norepinephrine receptor there,
too.
So if sympathetic activity
is being stimulated,
norepinephrine will land there
and will slow down digestion.
So if you've taken bio core,
if you want to know more--
there's actually names for all
of these forms of receptors
that I put there, just in
case you're extra interested.
But on the heart, I think
the coolest fact about it
is the beta blocker.
So the form of the
receptor on the heart that
responds to the
sympathetic nervous system
is actually called
a beta receptor.
And what beta blockers do,
they block the receptor,
the beta receptor.
So this is why beta
blockers are used
for slowing down heart
rate, reducing hypertension.
It's basically
blocking the effects
of the sympathetic
nervous system.
And Pat actually just
told me, which is great,
that the one drug that's
banned from the Olympics
are actually beta blockers,
because if you think about it,
a huge advantage would
be to be less stressed.
So if they're
blocking the receptor
on your heart that
responds to stress
and the sympathetic
nervous system,
you can see how it could
allow you to relax more.
So it's a fun fact.
So now we're going to
talk about the regulation
of the autonomic nervous
system, so what's
happening in the brain that's
resulting in norepinephrine
or acetylcholine being released.
And the center of regulation
is now the hypothalamus.
So we just talked
about the hippocampus,
so this is a different area of
the brain, the hypothalamus.
It's going to be very
important on Monday as well,
when Tom and Will talk
about the endocrine system,
because the
hypothalamus directly
affects the pituitary
gland, which is center
of your endocrine system.
So basically, the hypothalamus
here contains the cell bodies,
or is just one synapse away
from all the cell bodies
that project onto
the target organs,
from the spinal cord
to the target organs.
So basically, the hypothalamus
will tell the spinal cord
what to project onto the organ.
So an example of this
would be in your heart.
And this is actually
called the baroreflex.
And this is just an example of
how your hypothalamus is going
to help your body
maintain status quo,
so make sure that your blood
pressure's never too high,
your heart's beating
at a normal speed.
So let's say you're
hemorrhaging,
because I don't know, a
hyena just attacked you.
That's weird.
So anyways, you're hemorrhaging.
And you're losing
a lot of blood,
so your blood pressure's
going to go way down.
And you have these receptors
in your blood vessels
that are called baroreceptors.
And they'll say, OK, blood
pressure's way too low.
What do I do?
They're going to send that
info to the hypothalamus--
remember the hypothalamus,
center of regulation.
And the hypothalamus
will be in charge
of sending that
information along
to the spinal cord, which will
then project onto the heart
and tell it to beat faster.
Sympathetic nervous
system will be activated.
Beat faster, increase
my blood pressure,
so that you'll make up
for the loss of blood
that you just had.
And the opposite would happen
if your blood pressure is
getting too high or something.
Maybe the info will
be sent to your brain.
And then you can
decrease blood pressure
through the parasympathetic
nervous system.
So reptiles, everybody kind of
has that hypothalamus control
of the-- yeah.
Sorry, I had a question
about the [INAUDIBLE].
This is kind of a
[INAUDIBLE] question,
but is it actually stimulating
the sympathetic nervous system?
Or is it normally stimulating
the parasympathetic and then
stops the stimulation?
Oh, because remember,
one's on or off.
So like which one's normally on?
Do you guys know?
Anybody know?
There's just a baseline
balance [INAUDIBLE].
Yeah.
So what about mammals?
Mammals have emotions.
And we have an
emotional regulation
are in our brain that's
called the limbic system.
And we're going to learn
a whole lecture just
about the limbic
system in general.
But basically, it has everything
do with emotions, behaviors,
memories, all
mammalian type things.
So now we see this realm where
not just losing all your blood
can activate or stimulate
the nervous system
and cause a parasympathetic
or sympathetic response.
But now just seeing
someone you hate
can cause a sympathetic
response that's
very similar to
losing a lot of blood.
And this is pretty amazing.
Wildebeests, for instance,
if they see their enemies,
the info will be sent from
just the smell of their enemies
to the limbic system, project
onto the hypothalamus, spinal
cord, to the sympathetic
nervous system,
be like, I don't
like you response.
The sympathetic
nervous system wanting
to either fight or flight.
And then in the
realm of primates,
we also have our cortex.
And what the cortex does is
it makes thoughts and memories
really important.
So now, instead of just
having-- losing a lot of blood,
we're changing how
our body functions.
And now, not even
having to sense-- we
don't need to have a sense.
We can just think
about a thought.
And that can go ahead
and change the way
that every organ in
our body functions,
which is pretty amazing.
So when you're thinking
about a test, for instance,
you're going to
activate your cortex.
And this will activate your
limbic system, and then
your hypothalamus.
So that's known, actually, as
the triune system of the brain.
You have the cortex
in primates, mostly.
Then you have the limbic
system, mostly mammalian.
And then you have
the hypothalamus.
So it's going to go to each one
of these layers of the brain.
And just thinking
about a test can
cause a sympathetic
response, where
you start sweating, getting
nervous, stressed out.
And it's pretty amazing that
if you lost a lot of blood
in a reptile, we can stimulate
the same response just
thinking about
something, or thinking
about someone on the other
side of the world dying.
It's just amazing
what primates can do.
And an interesting
example of this-- and I
think we're having a lecture
on depression, so I don't
want to give it all away yet.
But if you think
about it, the symptoms
of depression, loss of
pleasure, pain pathways on,
don't want to have
sex, aren't in the mood
to eat, you're exhausted all the
time, a lot of these symptoms
are the same symptoms
you would see
if your sympathetic nervous
system was overly activated.
And we can see how the
cortex having bad thoughts
can go and activate that
system in the same way, links
to depression.
And the last thing
I wanted to talk
about in terms of the
autonomic nervous system
was the plasticity of it.
So we just learned the
plasticity in neurons,
in the synapses.
So that's when it
can change over time.
And the autonomic nervous system
can actually change over time,
in terms of how receptive,
or when it turns on and off.
And a molecular
example of this is
if you're a very
stressful person,
and you're stressing
all the time.
Well, then you need a
lot of norepinephrine.
What do you do if you're
stressing all the time?
You increase the
synthesis of the enzyme
called tyrosine
hydroxylase, I believe.
Yeah, it's up there.
And basically, this is
the rate limiting step
in making norepinephrine.
So if you increase
more of the enzyme,
you increase more of
the norepinephrine,
you can sustain the
stress response.
Another example,
cellular example,
is that we have projections from
the sympathetic nervous system
to the skin, eyes,
nose, everything
that's going on out there.
And let's say we
see something scary.
We can make those receptors more
sensitive to that scary thing.
So we can say, hey, it
actually smells that enemy.
We can make it seem scarier.
The sympathetic nervous
system can turn on faster,
so sensitization.
There's also the opposite
end of the spectrum,
where you habituate to things
that are going on outside.
So scary stimuli--
if you see a spider
in your room the
first time, you're
probably going to freak
out when you're younger.
Lots of sympathetic activity,
running away, fight or flight.
You decide to fly, because
I don't like spiders.
But basically, after a while,
second time you see a spider,
you're just like, oh,
this is still scary.
Maybe I'll run away.
The third time,
maybe you decide,
whatever, I'm just going to
leave it there at this point.
And you're habituated to it.
So you've made the thresholds
of your sensory receptors,
they don't care as much.
They don't respond as much.
And a last example, when we're
talking about cognitive thought
and the cortex and
what that can do
to change our autonomic
nervous system,
is an example of biofeedback
and blood pressure.
So basically, if you
have high blood pressure,
you can go into the
doctor's office.
And you have two options.
You can take medicine, or
you could try biofeedback.
And what they do
is they tell you
to think of a pleasant thought.
So think of your
favorite vacation,
or think of your
favorite person,
or just think of the
beach in general.
And what you'll see is that your
blood pressure will actually
decrease with a certain thought.
And then the doctor
will tell you to think
about that thought again.
Your blood pressure
will decrease.
And thinking more and
more about that thought,
helping your blood
pressure decrease,
what you do is you potentiate,
remember, you make stronger
the connection where a
cortical thought can go ahead
and activate more
parasympathetic tone,
have less sympathetic tone.
So we're potentiating
that pathway
by which a thought can cause
our blood pressure to decrease,
which is pretty cool.
So the take home points,
if you want to just know
what to remember from this.
Know the broad difference
between autonomic,
automatic, and the voluntary
nervous system, what we
talked about at the beginning.
Understand the neurotransmitters
involved in each,
and why you need two
types of receptors,
the inhibitory and excitatory.
Know one or two examples of
what the parasympathetic--
that's what PNS,
by the way, means--
and sympathetic nervous
system do to an organ.
So remember the heart,
the digestive tract,
the male reproductive system.
And then know a broad overview
of how the brain regulates
the autonomic nervous system,
so hypothalamus, cortex,
and we have the limbic system.
On Monday, we're going
over endocrinology.
So have a good--
For more, please visit
us at Stanford.edu.
