Brain Mapping: Possible Road to a Cure Dr. Mayank Mehta

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Nov 14, 2013 (3 years and 8 months ago)

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Dr. Mayank Mehta,
Professor
in the

Department of Physics,
Astronomy,
a
nd Neurology at
UCLA,
talks about a new technology mapping the brains of rats where the Alzheimer’s disease
strikes.

How
long have you been studying the brain?

Dr. Mehta:

I have been studying the brain for

more than

fifteen years.

When did you move in
to the virtual maze type of thing?

Dr. Mehta:

Around the time I moved to UCLA. L
ong ago my interest was understandin
g t
he
str
ucture of physical space time, w
hich
wa
s studied in physics by peo
ple like Einstein and
Newton. We wanted to see how
space and ti
me arise in the brain. For example,

I can ask you to
focus on an abstract point in space, and after a half an hour and

you’ll b
e ab
le to still find it.
There’s nothing there at that abstract point, t
here’s no light
,

there’s no sound
,

or smell,

but you
can sti
ll point to it. So what is that ‘space’? A
ll anima
ls perceive space naturally. But, to
understand how we perceive space, we
should be able to manipulate space.
So how do we
manipulate space to und
erstand how the brain processes? Y
ou make virtual reality
!


T
hat’s what you’re doing?

Dr. Mehta:

More than

two years of
hard work by these students and

post
docs

in our

labs
,

we
have
a
fully functional multi
-
sensory and noninvasive virtual reality system here
.

W
hat can you see through this that you couldn’t see before?

Dr. Mehta:

T
he
really interesting thing is that when the space

is going on, real space that we
are in
,

we can
not

manipul
ate it
. T
he real space is made up of a lot of things. Real space is
defined by the lights in the room clearly,
but
it’s also de
fined by smells, sounds,

stuff on the
floor
,

so we don’t know how the brain puts all this together. Now if we make virtual realit
y we
can control each one of these precisely. We can make the
virtual
space go faster, we can make
the space go slower,
and
we can make the space go backwards. We can
make the rat jump
through hoops or

we can make him ju
mp through worm holes. We can now
create all

kinds of
spaces

and understand how our brain puts together these different changing stimuli to create
space. This was not possible before.

Can

you see then how the brain perceives space?

Dr. Mehta:

Yes
. W
e have now developed technology to look i
nside the brain while the rat is
doing

this virtual world task. Since we have control over

the space that we have generated
, we

Brain Mapping: Possible Road to a Cure


Dr. Mayank Mehta


now know what he is

seeing because we have it under our control. That tells us pretty profound
things about what’s going on

in h
is brain and how space is being put together
.

What can you see happening in the mouse brain?

Dr. Mehta:

I
t turns out there is a part of the brain
, called the hippocampus,

which is critical for
learning and memory. It’s one o
f the oldest parts of the brain
;

it’s
literally
called the

old brain.
Now it turns out as the rats,

mice
,

or even humans start walking around in
the
real world

or in
virtual space, like

playing a little video game

with an avatar
, there are neurons
in the
hippocampus
which will fire at d
ifferent places in that vi
rtual world as if they

have a map of the
virtual environment or the real world. The question now

becomes how did this brain map of
space arise? The

map arises pretty much in the
very
fir
st trial. A human being or a rat gets in
to
a

virtual world or a real world an
d within seconds there is a map.

It’s
fascinating.

Let’s say the map was a real map;

before you had the United States and now you’re
putting in the roads, is that right?

Dr. Mehta:

T
here is no
t even a map b
ecause before you

came to this room you didn’t know how
this

room would look, where

the table

would be, where the chairs are; you didn’t know that, b
ut
you figured out that map instinctively as soon as you came in. We take it for granted
,

but it’s
really hard t
o even teach

a powerful computer

to make that map.

N
ow you’re making all the connections?

Dr. Mehta:

To some extent. I
t goes in both directions.

On one side
if

I were to ask you to
describe what

the map of the room

is

you’d point to different things. You would say there is a
wall here, a plant
there
, a table somewhere
, the sound of a water fountain, fragrances from the
kitchen…

T
he question is:
how do
es

your brain pu
t it all together to make a map and the
perception of

a room?

Now that’s a non
-
trivial process.

W
hen you say a map
,

when I walk through the door I instantly know to step around that
chair and that desk
,

and that’s the map?

Dr. Mehta:

Exactly. That’s the map,

your layout of the world. It’s the map that y
ou’r
e figuring out
on the fly, a
nd all animals have to do that.

So, we don’t know how they do it?

Dr. Mehta:

That’s exactly right, and we are fig
uring out how that happens. They have two parts
to it. O
ne is the stuff
out there in the world. There are

a lot of things out there in the world that
define what’s the map
, buildings, mountains, sounds, smells, etc. However,

there is the stuff
inside the brain too. There’s a lot of interesting electricity and chemistr
y that goes on inside the
brain;

which ha
s its own rules and rhythms. T
he match between the rules of the brain and rules
of the world define space. It’s pretty interesting.

A
re you doing this by mapping neurons?

Dr. Mehta:

Yes. W
e ha
ve been mapping the activity of

lots of neurons simultaneously w
hile the
animals ar
e

formi
ng maps of the world. S
urprisingly
,

the formation of the map also depends on
what goes on during sleep after you have
formed the map
. There’s a huge amount of research
which
shows that the map you have formed during exploration is

not the full story, it’s only a part
of the story. When you go to sleep, when you think you’re not doing anything
,

that map is
getting changed.

Is it taking everything that it’s learned through the day?

Dr. Mehta:

It seems l
ike it. T
he process is called
consolidation. I
t seems like what goes on is
you’re taking in what you learned during the day and what you learned in your life before that
and consolidating all of that to generate a map.

Right now what has been the most surpr
ising finding to you
?

Dr. Meh
ta:

The most surprising finding is that when these maps ha
ve been formed they are
dynamic; that’s number one. Y
ou think the world is the same as you’re walking around. We did
a very careful experiment and a r
at walks in a very simple world;

nothing complic
ate
d, his
behavior doesn’t change.

W
alks once, then walks a second time, in the same simple room on
precisely the same path, and everything seems constant, unchanged. But
already the brain’s
activity changes within one trial. Neuron
s become twice as active

within two trials and neurons

start to predict where the mouse is going to be based on just one experience. So in the first trial
,

the neurons are simply telling him you are next to the chair, you are next to the table, so on and
so forth. Within one or t
wo trials those neuron
s

start to

tell where you are going to be in a few
steps, which is crucial for navigation. In other words the neurons were initially saying where you
are but after a few trials they start to generate a mental image of where you will e
nd up along
the path, based on that brief experience. Put it simply, the neuron starts to predict your future
position in space! I
f you’re going anywhere you not only need to know where you are but you
also need to know wh
ere you’re going to end up. This i
s precisely what we found neurons are
doing, very quickly. T
hat’s one surprising finding. The second surprising finding is that
when
these rats or humans

are walking around, our brain

s activity apart from having this map
develops another interesting thing

called rhythm. The whole activity
of the space
-
mapping part
of the brain becomes rhythmic. This rhythm is generated by the brain on its own! We found
very recently

that this rhythm
codes th
e speed at which you are going.

So the faster you go
,

the
bigger

and faster

is the rhythm. Even more fascinating
is
that very rhythm that gets bigger when
you run faster is actually cruci
al for learning and memory and formation of maps of the world. I
f
you’re simply sitti
ng and do some other mechanism, that rhythm beca
me stronger and

you
would learn better.

On the other hand, when you go to sleep the rhythm goes away.

So I should always walk on a treadmill and read a book?

Dr. Mehta:

W
e
recently did similar

experiment on a treadmill
. We found that the rhythm does
beco
me bigger with increasing running speed on a treadmill, just like running in the real world,
but the rhythm does not get any faster at higher speeds on the treadmill but it does in the real
world. We are now working hard to understand why this happens and
what does this do to
learning and memory.
.

From what you do here
,

will it have any impact on human brains of why Alzheimer’s
happens or memory loss?

Dr. Mehta:

W
e hope that this will help us understand what goes wr
ong in Alzheimer’s disease.
In another s
tudy that we just did which we

published last year
,

we were looking at

a part of the
brain called the entorhinal cortex

where the A
lzheimer’s disease starts. So, w
e were looking at
the activity of those neurons when the rat was not
doing anything; t
he rat was simply sleeping.
You would think nothing should go on because he’s not going anywhere. Turns out throughout
the period of sleep there are these special neurons
in the entorhinal cortex
behave as if they
were remembering something. Not just every

now and then during sleep

but

for pretty much the
whole duration of sleep. These neurons were behaving as if they were remembering something.
Even more fascinating, this memory like activity in the entorhinal cortex was very powerful in
driving the activi
ty of map making neurons in the hippocampus.
So now you can see the
conn
ection that there’s this memory
-
like processes that are going on in the brain even when
you’re not activel
y trying to remember anything. The brain has its own dynamics and

its own
laws

of physics or biophysics that gover
n what the brain is doing. T
hose things are processing
stuff and if that goes wrong
,

clearly that will play a crucial role in loss of memory such as in
Alzheimer’s disease or PTSD where
the memories are pathological. I
t’
s a long way off fro
m here
to Alzheimer’s disease, b
ut we’re working on that.

Do you think we’ve got it?

Dr. Mehta:

We are getting there, especially with the new technology we are now developing. In
a few moments

you are going to see two experiments that w
e are doing. One is the experiment
where the rat is trying to find his way in a virtual world. Why virtual world? Because there we
can control the stimuli provided to him to form a map of space, he
cannot find his way based on
some scent mar
ks that he left

on the track;

that’s one experiment. You’re going to see the rat
actually behaving in the virtual world, finding his way, getting a reward, being happy, falling
asleep

in the virtual world as his virtual nest
,
and
behaving perfectly naturally except that
he’s
not going anywhere

in reality
. He’s fixed in one pl
ace the world is going by him b
ut he believes
he went to the
world.

Another experiment you are going to see is now instead of the rat being in
one place and the world going by
,

the
rat actu
ally goes t
o different places s
o he can see there
are differences. We can compare those two
things. Y
ou’re
also
going to see
is
how the brain
signal looks when the rat is going
somewhere in the real world or the virtual world,
or even when
the rat is sleeping. You’ll

see amazing patterns of activity come and go in the brain

as a function
of different behaviors
. You’ll be able to hear the activity of lots of neurons simultaneously while
the rat is doing these things.


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h purposes only. It is not to be used as a
prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional
interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy
of physician statements. Procedure
s or medicines apply to different people and medical factors;
always consult your physician on medical matters.





If you would like more information, please contact:


Mark Wheeler

Senior Media Relations Rep

UCLA Health Sciences Media Relations

mwheeler@mednet.ucla.edu



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