Transcriber: Mohand Habchi
Reviewer: Reiko Bovee 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 - that is "Neurons that fire together
wire together." Contiguity breeds connectivity. And this is a lesson that has been learnt 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 reconstruct 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 neurogenesis,
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 - the contiguities to be such
that we strengthen a pathway from A to B in the brain. And when we do this, overtime,
we strengthen the pathway. How do we do it? We stimulate one place, the other place.
We can stimulate lots of places. We got all these electrodes now,
arrays are being developed. We're going to be able to imagine
the locus of neural points that represents your grandmother
versus your grandfather. We should be able to strengthen
the memory of your grandmother by just stimulating the right connection
of points inside your head. So we're pretty excited
about what's going on now. I can't tell you everything
that we're doing, but I just want to close with a quote from that great Canadian philosopher,
Wayne Gretzky: "Skate where the puck is going to be." And what Wayne is telling us in this quote is that here's a tremendous
challenge and opportunity in association with what is now going on
in understanding how the brain works. I've been doing brain research,
I hate to tell you, 50 years now, and it has never been
as exciting as it is today. It is moving so fast, it sits right
Ar the confluence of genetics, imaging, cell signaling,
electrophysiology. And combining all of these technologies is going to give us
unprecedented capability to change the brain for the better. I look forward to the next 50 years. Thank you again. (Applause)
