Kind: captions
Language: en
how do you fix a brain that's not
working properly well until now the only
real option has been to open up the
skull implant electrical or optical
fibers or even remove parts of the brain
if you do something like surgery or
ablation even with ultrasound that's an
irreversible one-time procedure but this
scientist has a different idea do you
want to introduce yourself yeah sure
yeah i'm uh mikhail shapiro or should we
where should i look
you can look at me yeah okay
yeah i'm mikhail shapiro i'm a professor
of chemical engineering at caltech
everything that we try to do is to make
it non-invasive meaning that we don't
want to have any kind of surgery
to open up the skull and implant an
electrode or we don't want to have to
open up the skull to shine light
onto the neurons we want to do it using
sound waves which is one of the few
forms of energy that can be focused deep
inside of the tissue and can actually
permeate through things like the skull
even the human skull this is a curved
transducer so you can see there's a
slight
curvature in it that will cause the
sound waves to get concentrated
a few centimeters in front of the face
of this transducer for now the research
is being conducted on mice and the idea
is to be able to turn on and off
specific brain regions at will without
invasive surgery so the trick that we
employ here
is that we take something that's
traditionally been a really big problem
in neuroscience drugs and we turn it
into an advantage so the problem is that
the brain has what's called the blood
brain barrier which
lines the blood vessels of the brain and
prevents molecules in moving from the
bloodstream into the brain but in their
procedure they open the blood-brain
barrier in carefully targeted regions of
the brain so to do this we introduce
little bubbles into the bloodstream air
bubbles
bubbles of air but they are uh safe
bubbles so this is this is a an fda
approved clinically used like ultrasound
contrast agent they're microns in scale
okay tiny air bubbles so tiny little air
bubbles um that we introduce into the
into the bloodstream and so they're
circulating everywhere
and then wherever we apply the
ultrasound the sound waves cause the
bubbles to expand and contract in size
and as they're doing that they push
against the blood vessel walls and kind
of massage them open so they get that
blood brain barrier that's normally
caused by really tight junctions between
cells to open just a crack
so that now molecules can get out into
the brain and by using the ultrasound
you can target just specific
areas of the brain where you want to
open the blood-brain barrier and leave
the rest of the brain alone exactly once
the blood-brain barrier is open the
scientists inject a specially made virus
that would normally not be able to pass
into the brain these viral vectors which
are viruses that we have hijacked so
that instead of them introducing their
dna into the cells they're going to
introduce the dna that we want and what
this gene produces are these receptors
that will go onto the neuron these
receptors have been modified so they no
longer respond to neurotransmitters that
are natively present inside the brain
and will instead respond to a drug that
we can inject that will activate just
those receptors and not act on anything
else
i'll tell you when we get to a part
where
your camera is going to get sucked into
the magnet before it happens thank you
i appreciate that
so this
big machine here
is what generates the sound waves that
we use this little device
will get installed on here and then
we're going to have a mouse underneath
and then this entire thing is going to
go into
the
mri scanner
is this a special ultrasound for
mice both the mri is special for mice
because as you can see from the bore
that's in the middle
yeah human's not going to fit in there
yeah we'd have to be a really small
human and then our ultrasound system
also is designed for these kind of small
animals and that squeaking sound that
i'm hearing that's not actually mice in
there
that's the mri yeah how strong is the
magnetic field in there
uh inside the scanner it's seven tesla
whoa yeah so it's going to give us an
image of the anatomy of the brain and
allow us to target the focus of this
ultrasound transducer to precisely the
part of the brain where we want to open
the blood-brain barrier there will be
four bright spots that will appear on
the brain just about here so this is the
opening of the barrier between the blood
and the brain
that allows
a diffusion of what is essentially a
magnetic resonance imaging dye that
shows up during the mri imaging this is
the hippocampus hippocampus is a fairly
large structure that's important in the
formation of memory and this is the one
that we targeted in our recent study to
modulate the memory of mice we
targeted the hippocampus which is this
part of the brain that's necessary for
the formation of certain kinds of
memories and using our technique we can
address just the neurons within the
hippocampus and when we give a drug
those neurons get shut down and then we
can do behavioral experiments where we
did a memory task where we put the mice
into a particular environment and
checked the next day by bringing the
mice back into that same environment
whether or not they could remember it
and for the mice that were treated with
the ultrasound with the receptors
through the viral vectors and given the
drug that activates these receptors that
shut down the hippocampus
those mice were not able to remember so
we could tell that we were successfully
able to
inhibit or prevent memory formation
because the effect depends on when you
give this drug and how much of the drug
you give you can have reversible turning
on or off of the effect that you're
trying to produce so for example
shutting down the part of the brain
that's causing a seizure so another part
of the brain that we're pretty
interested in is called the ventral
tegmental area which is a part of the
brain that uses the neurotransmitter
dopamine
and is involved in things like
motivation
and addiction and initiation and control
of movement
and if we can gain control over the
neurons in that area it might someday be
useful for treatments for some of these
motivational or effective
disorders like addiction or depression
could you use this to control people's
brains like by playing ultrasound you
know some area no there is not a chance
at least using our technology that you
could be walking around and we could be
controlling your brain remotely
if that's what you're worried about
not yet anyway
that is not our goal
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