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  • Thank you very much for that generous introduction.

  • It's a pleasure to be here.

  • Today my subject is "Enhancing Brain Plasticity."

  • And what I'm going to do in the next few minutes hopefully is

  • to tell you a little bit about what brain plasticity is, how it works,

  • what we're doing to try to enhance it,

  • and what you can do to enhance the plasticity of your brain.

  • So at end of these 18 minutes,

  • I hope that all of that will transpire.

  • So, what is brain plasticity?

  • Well, brain plasticity is the process by which your brain changes

  • depending on what has happened to it.

  • And brain plasticity would include, for instance, memory.

  • If you remember this lecture tomorrow - and I hope you will -

  • it's because of brain plasticity.

  • But brain plasticity is more than memory.

  • It's the process by which your brain is involved in learning,

  • say a new skill, learning to ski or play Sudoku; do things like that.

  • It's the process by which you recover from brain damage of various sorts,

  • for instance, after a neurotrauma or a stroke.

  • and it's also how you adapt to the fact

  • that you now weight 20 pounds more after Christmas,

  • and all your biomechanics are different, yet you still have to walk gracefully.

  • So all of that is brain plasticity.

  • Now, most of what you need to learn about brain plasticity in this talk

  • can be summarized in the following slogan

  • - OK? So after this, you can just go to sleep -

  • slogan is "Neurons that fire together wire together."

  • Contiguity breeds connectivity.

  • And this is a lesson that has been learn in the last 20 or 30 years of neuroscience research.

  • I'm going to tell you a little bit about just how that actually works.

  • So let's focus at the beginning on one part of neuroplasticity,

  • the plasticity that we think of as memory.

  • So what's a memory anyway? What is a memory?

  • Well, I submit to you that a memory is nothing more than your ability to relconstruct the whole from a degraded fragment.

  • Nothing more than that. So what do I mean by that?

  • Let's talk about a specific memory.

  • How about the memory of, I don't know, your grandmother?

  • You see all these points of light behind you.

  • Imagine that they're all points of activity inside your brain.

  • If you look at this part of the brain here in the back, the visual cortex...

  • Imagine that this is what your grandmother looked like,

  • the activity that your grandmother evokes in your visual cortex,

  • during your interaction with her.

  • Here's the auditory cortex, and this is the sound of her voice,

  • or the things, the wise things she said to you.

  • You know, this is the parietal cortex, the somatosensory cortex,

  • this is the touch of her skin, the texture of her clothes.

  • Up here in the smell cortex is the smell of her perfume, things like these.

  • All of these points of light represent activity that occurs in your brain

  • while you're interacting with your grandmother.

  • And now remember the slogan: "Neurons that fire together wire together."

  • So as you interact with your grandmother over the years,

  • the sound of her voice, the texture of her clothes,

  • what she looks like, the smell of her perfume,

  • the taste of her cookies, all those things associate.

  • They come together, they're active at the same time,

  • and neurons that fire together wire together.

  • Many of you have probably not seen your grandmother for a very long time.

  • She may be dead. So what happens?

  • You're walking, I don't know, along Robson Street,

  • and you walk past the store, and you smell the perfume.

  • Out of that store comes the perfume.

  • And what happens? Your grandmother is right there.

  • All of her is right there: the sound of her voice,

  • what she looks like, the texture of her clothes,

  • all the other attributes of your grandmother

  • can be evoked just by stimulating one part of it.

  • And that's because neurons that have been firing together for years

  • have now wired together.

  • You can enter the circuit at any point.

  • A piece of music that your grandmother liked

  • is enough to activate that circuit as well.

  • A picture of her is enough to activate it.

  • And that's what we think is a key part of the memory process,

  • and that's why neurons firing together are so important.

  • In neuroscience now we can actually make neurons...

  • Here we have two neurons,

  • and these neurons are in a mouse brain, but what we've done is

  • we've taken two neurons, and we've stuck into them a gene that we borrowed from jellyfish.

  • It's the gene that makes jellyfish glow green at night,

  • and we've stuck it into these two neurons, and now they too are glowing green,

  • and you can see two neurons connected to each other.

  • The soma is the cell body, the axon is the sending end of the neuron,

  • the dendrite is the receiving end of the neuron.

  • And what we can do is we can take these two neurons,

  • and force them to associate.

  • We can take the neuron on the left and tickle it with an electrical stimulus,

  • zap! zap! zap!, we make it fire.

  • And if we make it fire hard enough, we can get through the axon,

  • we can activate the next neuron, the neuron on the right.

  • Neurons that fire together wire together.

  • So we go prrp! prrp! prrp! and after a time, what we find is if we make those two neurons associate

  • the connection between them will get stronger,

  • and we're understanding the mechanisms by which that works.

  • Now the way in which the two neurons connect to each other is right over here

  • at a place called the synapse.

  • Over the last decades, neuroscience has really understood the synapse in ways that were just not possible before.

  • So the next slide gives you an illustration

  • of what the synapse looks like.

  • Those little blue dots on the top are the transmitters released by the axon,

  • and then they activate all of these receptors,

  • and all of that machinery in the next neuron,

  • and ultimately that causes the neuron to fire.

  • But you know there is much more to it,

  • It's these receptors that are actually very important.

  • You see this receptor? It's called an AMP receptor.

  • It's kind of boring. If you put more in, more comes out.

  • In other words, if you give it a weak stimulus, it gives a weak response,

  • if you give it a stronger stimulus, it gives you a stronger response,

  • if you give it a really strong stimulus, it gives you a really strong response called linear.

  • Look at this kind, the NR receptor, also called the NMDA receptor.

  • It's very interesting. Very undemocratic receptor.

  • It hates weak inputs: you give it a weak input

  • not only does it not respond, but it actually goes negative.

  • You give it a slightly stronger input; still not very interesting.

  • You give a strong input; it goes crazy.

  • And when it goes crazy, what it does is it activates all this machinery down here,

  • and the effect of all that machinery is

  • to put in more of these ordinary boring receptors.

  • What that means is if you can tickle the fancy of this NMDA receptor,

  • you'll put in more of these ordinary AMPA receptors into the synapse,

  • and then the synapse will become stronger.

  • And that actually seems to be the core mechanism of memory,

  • of strengthening connections between two neurons,

  • of how strong inputs and contiguity can result in a stronger synapse.

  • And that's actually how we think you remember today's lecture.

  • (Laughter)

  • "So OK Max. That's all been great biochemistry.

  • I'm all excited. Fine. Good. Well, what have you done for me lately?

  • How's my memory going to improve from all this?"

  • I can tell you that scientists are working very hard.

  • All of this understanding is leading to new strategies and therapies.

  • If you actually look here, it turns out that if you block this,

  • this is very important in getting this whole process to happen.

  • We're working on drugs that will tickle this pathway

  • to give you a better memory.

  • But we're not there yet.

  • It turns out that there's a crucial structure in your brain

  • that seems to be actually very important for your memory.

  • It's called the hippocampus.

  • So they're all these points of light on the outside of your cortex.

  • They all funneled down to the hippocampus

  • which again represents the memory trace

  • in a compressed and higher form.

  • We can now record the activity of hundreds of points in the hippocampus,

  • hundreds of cells, as animals, for instance, run through a maze.

  • What we can do now is we an understand the functions of the hippocampus so well

  • that we can actually, without knowing where the animal is, we can say:

  • "These are the cells that are active now - the animals of the first choice point -

  • Now is at the second choice point. Now is at the third choice point."

  • And we can hear all this simply by recording the activity of all these neurons inside the hippocampus.

  • I want to tell you about an experiment that was done at MIT about ten years ago by Matt Wilson.

  • He was studying the hippocampus

  • as the rat was learning the maze,

  • he was going through the first choice, blah, blah, blah.

  • The experiment ends. He closes up the apparatus,

  • the animal sitting in the vestibule of the maze now, not in the maze,

  • and he starts to write up his lab notes.

  • He's still listening to all these neurons.

  • What he finds is while he's writing up the notes, he hears the neurons, you can hear them on loudspeaker.

  • The animals running through the maze.

  • How could that be?

  • Well, it turns out he goes over,

  • he looks at the animal, the animal is asleep,

  • but the hippocampus is still running through the maze

  • while the animal is asleep.

  • And there is now overwhelming evidence that what actually happens at night,

  • every night, after you learned stuff during the day is

  • that during sleep you replay and rebroadcast the memories of the day

  • back out from your hippocampus to the rest of your cerebral cortex,

  • rehearsing those memories again,

  • strengthening the association among all those points of light.

  • So what's my advice if you want to to improve plasticity?

  • Get a good night's sleep. It's very important.

  • Here's another thing you can do if you want to improve your memory capabilities and your brain plasticity,

  • and that is do physical exercise.

  • Do physical exercise.It used to be thought that we already had all the brain cells

  • we're ever going to have; that's not true.

  • We're actually making thousands of new brain cells every day,

  • and you can double or triple the number of brain cells

  • that you make next week by doing physical exercise.

  • Here's an experiment which we did, again, in rats,

  • where we can paint the new baby brain cells red,

  • the ordinary cells are green.

  • We take animals, we put them in an enriched environment,

  • We have other animals in an impoverished environment,

  • we find the enriched environment animals make more cells,

  • and we fractionate the environment;

  • we consider social cues, cognitive stimulation,physical stimulation.

  • What's important?Physical exercise.

  • More important than having friends, more important than playing Sudoku,

  • more important than all that stuff; do physical exercise.

  • (Laughter)

  • So what we're trying to do is to understand what actually happens in the brain when you do exercise.

  • And we're understanding there're growth factors that go on,

  • parts of these NR2B receptors are turned up,

  • and the entire plasticity machinery is turned on

  • along with these new baby cells.

  • We have a very good target now,

  • and we're actually working to develop a drug

  • that will enhance your neurogenesins, your ability to produce new brain cells.

  • And, by the way, this happens most in hippocampus I told you about.

  • And we're working very hard to basically develop that drugs

  • so you won't have to do all that messy exercise,

  • or hopefully, it will be synergistic with exercise.

  • So you can make three times as many more brain cells with physical exercise

  • , maybe three times as many,

  • again, with the drug and physical exercise.

  • So, there's been a lot of work on understanding...

  • There's been a lot of work

  • on looking at what happens in humans who do exercise,

  • and this is a longitudinal study that we're involved with.

  • As you get older,

  • your hippocampus shrinks along with everything else in your brain,

  • but if you look at the red group,

  • what you can see is that in a one-year longitudinal study,

  • the control group is doing stretching,

  • the experimental group is doing physical exercise,

  • the volume of the hippocampus doesn't shrink,

  • and in fact, it even gets bigger.

  • So what's my message? Do exercise.

  • We're trying to understand what kind of exercises you should be doing.

  • Here's a study by Teresa Liu-Ambrose from our center,working with a group of women in Dunbar.

  • What she finds actually is that cardio is important,

  • but actually doing weights is also surprisingly important.

  • So do both cardio and resistance training,

  • because that will actually enhance your cognitive performance.

  • One of the things we've been able to achieve in the last few years in the field of brain imaging,

  • is that not only we can see what parts of the brain are active,

  • but we can now actually see the pathways in the brain.

  • And we can see how they change as a function of usage.

  • And this slide shows you this.

  • Now, what we're learning then is under certain circumstances,

  • pathways can be too weak or perhaps even too strong.

  • And we're learning how to modulate the strengths of brain pathways.

  • There's a new technology,called Transcranial Magnetic Stimulation that Lara A. Boydis using in our Center.

  • We put somebody in this apparatus,

  • and we can stimulate one place in the brain,

  • or several places in the brain.

  • And what we can do again now, is to literally arrange

  • - remember, neurons that wire together fire together -