that we're at in the history of neuroscience,

in the history of science really,

because scientists are helping to decipher

what you could arguably say

is the most complex structure in the universe.

( applause )

When I was still a tenured professor,

now I'm just a mere mortal,

when I was still a tenured professor at Caltech

and I could leap over tall buildings,

I was, um... My main pursuit was studying consciousness

the neural basis of consciousness.

And in particular I felt the best way to pursue that

was to work on theoretical ideas, but also to pursue

experiments in humans, 'cause if there's one thing

we know for certain about consciousness,

is that most of us are conscious most of the time.

In order to understand anything about the brain

and ultimately about psychology, we have to understand neurons.

We know a lot about nerve cells in post-mortem, in dead brains

and of course in animals. But there's a rare occasion

when you can actually listen in

to the way neurons talk to each other,

and that's during neurosurgery.

So in some subset of patients, that have epileptic seizures,

there's an idea that if you can locate

from the place in the brain from which the seizure originates,

and if you can then surgically remove that,

then in many cases depending on the type of epileptic seizure

the seizures will go away.

Now in some patients you can't locate it from the outside,

so then what the neurosurgeon does, implants up to

12 microelectrodes into the patient's head.

And so you can essentially triangulate.

When the patient has a seizure you can triangulate,

and then you can pinpoint where the seizure originates.

So now in principle we can listen to individual neurons.

And I say listen because the way they talk to each other

is they're sending out these brief electrical pulses

called action potential or spikes.

You can put them on a monitor

and you can actually listen to them.

( popping noises )

So these are actually neurons, nerve cells,

in a brain of a patient that are chatting to each other.

We don't--we're only beginning to understand

the code that they use to talk to each other.

But we can pick up this signal

and it's very similar in animals.

So the patient is conscious, you can do all sorts of games

with the patients or you can show him or her images.

So what we did, we probed and we showed different things

to the patients because we wanted to uncover

what is the trigger, what turns these individual neurons on?

See here, what you can see, we show this image of a spider,

of an animal, of the Eiffel Tower,

of a bunch of Kobe Bryant,

of a bunch of other famous people,

and here, of an actress called Jennifer Aniston.

Some of you may know her, she's a famous Hollywood actress.

But now, if you show images of Jennifer Aniston

the neuron will respond... ( makes buzzing noise )

Very reliable, on each trial.

The neuron didn't respond at the time she was married

to another famous actor, and, uh...

( audience laughing )

And the neuron didn't respond to that.

This is now in the textbook

and is called "Jennifer Aniston neurons".

So the idea is that things that you're very familiar with

like actresses or actors, politicians,

your spouse, your kids, your workers, your car,

your dog, anything that you see again and again

your brain abstracts

and represents by a bunch of neurons.

Not one, this isn't just one Jennifer Aniston neuron.

There may be 10,000, or maybe even more neurons

that respond relative specifically

to Jennifer Aniston.

And so the idea is this tells us something

about the way neurons...

The things that neurons care about.

So in this high-level part of the brain,

they care about things that we care about.

It's not surprising. I mean, we care about abstract things

like people and the relationship,

or like idea, concept things

like justice or democracy or America or Afghanistan,

all those things, and there will be groups of neurons

that very specifically respond to that

when you think about those things.

So you can do a lot of research at that level.

Um, so this is a neuron.

Here you have its sort of input region.

This is called the dendrite, in red.

And then here at the cell body

there's a lot of electric machinery

that we understand quite well.

It generates this action-- this pulse

when it's sufficiently excited,

and then it sends out that pulse onto the wire.

This is the output wire, it's very complicated.

And every time there's a connection

this is indicated in yellow and that's a synapse.

The synapse is a contact point between two neurons.

And how much one neuron influences the next neuron

is encoded in the strength of that synapse.

And all the evidence shows that a memory,

like the memory of my first kiss,

or the memory that I know what Julius Caesar said

when he was killed by his friend Brutus,

all that sort of memory is encoded

in the strength of billions of synapses

that constitute memory and that also ultimately

give rise to consciousness, the feeling of something.

What really gives rise to thought and consciousness

and memories is the cerebral cortex.

The cerebral cortex is really a sheet.

It's a pizza. It's pretty much...

Think of a pizza that's two to three millimeters thick,

pretty much like my vest here, two to three millimeter.

It's this size, and we've got two of them,

but they're highly folded.

And this is a computational tissue

that evolution invented roughly 200 million years ago.

It's common to all mammals, and it gives rise

to our identity, who we are, our feelings, our memory

our sense of selves.

And we at the Allen Institute and many, many other scientists

are trying to understand what is the universal...

what is the, sort of the algorithm,

what is the computation that's performed

within this dense forest of 100 billion neurons?

It's 100 billion trees that give rise to all of this.

So now what we're gonna do, we're gonna zoom in

in this last movie I'll show you.

We're gonna zoom in onto one piece, a sliver here

that's incredible thin.

It turns out for those of you who know about numbers,

twelve micrometers in thickness.

That's maybe a tenth of the width of a human hair.

It's very, very thin but we're gonna zoom in, in great detail

because the more we look, the more details we see.

I show this because the one thing

that you're confronted with is overwhelming complexity.

Each new generation of measurement techniques,

of microscopes, reveals more and more complexity.

It has to be complex because ultimately it has to give rise

to the subtlety of the human mind.

So what we'll see here is a piece of cortex

from the mouse brain. Here again is one of those neurons

just like the one we showed before.

You'll see a whole bunch of them, so we're gonna take a trip

with cool music, that starts up here

and that goes slowly down here.

And it visualizes every single synapse,

so what you're gonna see are three colors.

You'll see in high detail, you see magenta.

Each magenta pointer, each point is a synapse.

As I said, they are-- In this piece

there's gonna be a couple of billion synapses.

Green is a subset of one particular type of neuron,

and the blue color you see is tubulin.

It's dendrites and axons of other neurons.

This is one millimeter again, so the millimeter

is half the size of the width of a grain of rice.

All right, and now...

( music playing )

So it's a mouse brain.

The common laboratory mouse.

The size of the brain is roughly a sugar cube.

And that's where we'll zoom in.

Just remember, the magenta are the synapses.

The green is one set of neurons.

They happen to be called Layer Five for the experts.

And blue is tubulin that shows the wiring of axons.

And now we'll go through this cortex.

( applause )

Good evening.

So you might think after seeing that movie

that it's hopeless, that we can never understand anything

about something so complicated.

Um, so what I want to do

is to say that in fact we have learned enough

not only to understand some fundamental things

about how the brain works,

but also to intervene in ways where we can restore

lost functions, and I want to give you

just two examples of the kinds of things

that we can do because of our understanding of the brain.

So the first one is one in which...

where technology we have is going to allow us,

allows us to write into the brain,

to actually do something to transform the brain

by intervening in brain circuits.

So, let me just explain.

So every day when you move around,

your brain is working to produce movements,

and there's a very important chemical in your brain

called dopamine that comes from the bottom of the brain

in the brain stem, and it comes up

and basically dopamine is oozed all over your brain,

and in many areas it's sort of, uh...

...your brain is taking a bath in dopamine.

In some cases, the dopamine neurons degenerate, they die.

In fact, in all of us, we lose a little bit as we age.

But if these neurons die,

the circuits don't work properly and you get something

that James Parkinson described in 1817

as "the shaking palsy".

And what happens here is, you can see this lady

who has lost many of her dopamine neurons.

She has the shaking palsy.

You have a tremor, you can't move, you're rigid,

and you have difficulty initiating movement.

It's a severely debilitating disease,

and it's because of the loss of dopamine.

Now we can't put dopamine back in the brain very well.

There are some pills, but it doesn't work

exceptionally well in all cases.

But what we can do, is we can put

a stimulating electrode about the size of a small soda straw

that has the ability

to electrically stimulate at the end,

and we can, by turning on this stimulator

we can tickle these brain circuits and make them act

as if they had dopamine back again,

so they work again.

And as a consequence, we have a very remarkable result

when we turn on this stimulation.

So here is the same lady, after the electrical stimulation

has been turned on, and you can see

the shaking, the tremor, the rigidity is gone.

And this is an amazing reawakening

of these motor circuits. They are no longer held slave

to this disruption that's there with the lack of dopamine.

This kind of intervention in brain circuits

to rebalance, or what we call "neuromodulation",

modulating these brain circuits back to normal,

is now being tried in a large number of other disorders,

and as far ranging as dementia, Alzheimer's disease.

Imagine now we could bring that circuit back