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  • We live in in a remarkable time,

  • the age of genomics.

  • Your genome is the entire sequence of your DNA.

  • Your sequence and mine are slightly different.

  • That's why we look different.

  • I've got brown eyes;

  • you might have blue or gray.

  • But it's not just skin-deep.

  • The headlines tell us

  • that genes can give us scary diseases,

  • maybe even shape our personality,

  • or give us mental disorders.

  • Our genes seem to have

  • awesome power over our destinies.

  • And yet, I would like to think

  • that I am more than my genes.

  • What do you guys think?

  • Are you more than your genes?

  • (Audience: Yes.) Yes?

  • I think some people agree with me.

  • I think we should make a statement.

  • I think we should say it all together.

  • All right: "I'm more than my genes" -- all together.

  • Everybody: I am more than my genes.

  • (Cheering)

  • Sebastian Seung: What am I?

  • (Laughter)

  • I am my connectome.

  • Now, since you guys are really great,

  • maybe you can humor me and say this all together too.

  • (Laughter)

  • Right. All together now.

  • Everybody: I am my connectome.

  • SS: That sounded great.

  • You know, you guys are so great, you don't even know what a connectome is,

  • and you're willing to play along with me.

  • I could just go home now.

  • Well, so far only one connectome is known,

  • that of this tiny worm.

  • Its modest nervous system

  • consists of just 300 neurons.

  • And in the 1970s and '80s,

  • a team of scientists

  • mapped all 7,000 connections

  • between the neurons.

  • In this diagram, every node is a neuron,

  • and every line is a connection.

  • This is the connectome

  • of the worm C. elegans.

  • Your connectome is far more complex than this

  • because your brain

  • contains 100 billion neurons

  • and 10,000 times as many connections.

  • There's a diagram like this for your brain,

  • but there's no way it would fit on this slide.

  • Your connectome contains one million times more connections

  • than your genome has letters.

  • That's a lot of information.

  • What's in that information?

  • We don't know for sure, but there are theories.

  • Since the 19th century, neuroscientists have speculated

  • that maybe your memories --

  • the information that makes you, you --

  • maybe your memories are stored

  • in the connections between your brain's neurons.

  • And perhaps other aspects of your personal identity --

  • maybe your personality and your intellect --

  • maybe they're also encoded

  • in the connections between your neurons.

  • And so now you can see why I proposed this hypothesis:

  • I am my connectome.

  • I didn't ask you to chant it because it's true;

  • I just want you to remember it.

  • And in fact, we don't know if this hypothesis is correct,

  • because we have never had technologies

  • powerful enough to test it.

  • Finding that worm connectome

  • took over a dozen years of tedious labor.

  • And to find the connectomes of brains more like our own,

  • we need more sophisticated technologies, that are automated,

  • that will speed up the process of finding connectomes.

  • And in the next few minutes, I'll tell you about some of these technologies,

  • which are currently under development

  • in my lab and the labs of my collaborators.

  • Now you've probably seen pictures of neurons before.

  • You can recognize them instantly

  • by their fantastic shapes.

  • They extend long and delicate branches,

  • and in short, they look like trees.

  • But this is just a single neuron.

  • In order to find connectomes,

  • we have to see all the neurons at the same time.

  • So let's meet Bobby Kasthuri,

  • who works in the laboratory of Jeff Lichtman

  • at Harvard University.

  • Bobby is holding fantastically thin slices

  • of a mouse brain.

  • And we're zooming in by a factor of 100,000 times

  • to obtain the resolution,

  • so that we can see the branches of neurons all at the same time.

  • Except, you still may not really recognize them,

  • and that's because we have to work in three dimensions.

  • If we take many images of many slices of the brain

  • and stack them up,

  • we get a three-dimensional image.

  • And still, you may not see the branches.

  • So we start at the top,

  • and we color in the cross-section of one branch in red,

  • and we do that for the next slice

  • and for the next slice.

  • And we keep on doing that,

  • slice after slice.

  • If we continue through the entire stack,

  • we can reconstruct the three-dimensional shape

  • of a small fragment of a branch of a neuron.

  • And we can do that for another neuron in green.

  • And you can see that the green neuron touches the red neuron

  • at two locations,

  • and these are what are called synapses.

  • Let's zoom in on one synapse,

  • and keep your eyes on the interior of the green neuron.

  • You should see small circles --

  • these are called vesicles.

  • They contain a molecule know as a neurotransmitter.

  • And so when the green neuron wants to communicate,

  • it wants to send a message to the red neuron,

  • it spits out neurotransmitter.

  • At the synapse, the two neurons

  • are said to be connected

  • like two friends talking on the telephone.

  • So you see how to find a synapse.

  • How can we find an entire connectome?

  • Well, we take this three-dimensional stack of images

  • and treat it as a gigantic three-dimensional coloring book.

  • We color every neuron in, in a different color,

  • and then we look through all of the images,

  • find the synapses

  • and note the colors of the two neurons involved in each synapse.

  • If we can do that throughout all the images,

  • we could find a connectome.

  • Now, at this point,

  • you've learned the basics of neurons and synapses.

  • And so I think we're ready to tackle

  • one of the most important questions in neuroscience:

  • how are the brains of men and women different?

  • (Laughter)

  • According to this self-help book,

  • guys brains are like waffles;

  • they keep their lives compartmentalized in boxes.

  • Girls' brains are like spaghetti;

  • everything in their life is connected to everything else.

  • (Laughter)

  • You guys are laughing,

  • but you know, this book changed my life.

  • (Laughter)

  • But seriously, what's wrong with this?

  • You already know enough to tell me -- what's wrong with this statement?

  • It doesn't matter whether you're a guy or girl,

  • everyone's brains are like spaghetti.

  • Or maybe really, really fine capellini with branches.

  • Just as one strand of spaghetti

  • contacts many other strands on your plate,

  • one neuron touches many other neurons

  • through their entangled branches.

  • One neuron can be connected to so many other neurons,

  • because there can be synapses

  • at these points of contact.

  • By now, you might have sort of lost perspective

  • on how large this cube of brain tissue actually is.

  • And so let's do a series of comparisons to show you.

  • I assure you, this is very tiny. It's just six microns on a side.

  • So, here's how it stacks up against an entire neuron.

  • And you can tell that, really, only the smallest fragments of branches

  • are contained inside this cube.

  • And a neuron, well, that's smaller than brain.

  • And that's just a mouse brain --

  • it's a lot smaller than a human brain.

  • So when show my friends this,

  • sometimes they've told me,

  • "You know, Sebastian, you should just give up.

  • Neuroscience is hopeless."

  • Because if you look at a brain with your naked eye,

  • you don't really see how complex it is,

  • but when you use a microscope,

  • finally the hidden complexity is revealed.

  • In the 17th century,

  • the mathematician and philosopher, Blaise Pascal,

  • wrote of his dread of the infinite,

  • his feeling of insignificance

  • at contemplating the vast reaches of outer space.

  • And, as a scientist,

  • I'm not supposed to talk about my feelings --

  • too much information, professor.

  • (Laughter)

  • But may I?

  • (Laughter)

  • (Applause)

  • I feel curiosity,

  • and I feel wonder,

  • but at times I have also felt despair.

  • Why did I choose to study

  • this organ that is so awesome in its complexity

  • that it might well be infinite?

  • It's absurd.

  • How could we even dare to think

  • that we might ever understand this?

  • And yet, I persist in this quixotic endeavor.

  • And indeed, these days I harbor new hopes.

  • Someday,

  • a fleet of microscopes will capture

  • every neuron and every synapse

  • in a vast database of images.

  • And some day, artificially intelligent supercomputers

  • will analyze the images without human assistance

  • to summarize them in a connectome.

  • I do not know, but I hope that I will live to see that day,

  • because finding an entire human connectome

  • is one of the greatest technological challenges of all time.

  • It will take the work of generations to succeed.

  • At the present time, my collaborators and I,

  • what we're aiming for is much more modest --

  • just to find partial connectomes

  • of tiny chunks of mouse and human brain.

  • But even that will be enough for the first tests of this hypothesis

  • that I am my connectome.

  • For now, let me try to convince you of the plausibility of this hypothesis,

  • that it's actually worth taking seriously.

  • As you grow during childhood

  • and age during adulthood,

  • your personal identity changes slowly.

  • Likewise, every connectome

  • changes over time.

  • What kinds of changes happen?

  • Well, neurons, like trees,

  • can grow new branches,

  • and they can lose old ones.

  • Synapses can be created,

  • and they can be eliminated.

  • And synapses can grow larger,

  • and they can grow smaller.

  • Second question:

  • what causes these changes?

  • Well, it's true.

  • To some extent, they are programmed by your genes.

  • But that's not the whole story,

  • because there are signals, electrical signals,

  • that travel along the branches of neurons

  • and chemical signals

  • that jump across from branch to branch.

  • These signals are called neural activity.

  • And there's a lot of evidence

  • that neural activity