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The brain is made of, maybe
thousands of different kinds
of cells called neurons that
are built into very dense,
inter-mesh networks.
Each of these neurons computes
using electricity. The cycle
implements behavior, and
thought and emotion. All these
different kinds of things. We
also think that deficits in
these electrical computations
underlie many brain disorders
that affect over a billion people
around the world.
In optogenetics, what we're doing
is we're putting molecules, that
convert light into electricity,
into neurons - the cells of
the brain. Then when we shine
light on those neurons, light
gets converted to electricity
and allows us to turn on or off
those cells. The goal here is to
find a way to control the
electrical activity in some cells
and not others in the network.
To do that we had to turn to
the natural world. It turns out
that throughout all the kingdoms
of life - in plants, in funguses,
and bacteria and so on - you can
find photosynthetic or photo-
sensory molecules that convert
light into electricity. So we
borrow these molecules from
nature, and then using tricks
from the field of gene therapy
we can put them into neurons.
Now, these molecules can convert
light into electricity and they
do it just in the neurons that
we want to control. And not all
their neighbors. So we can
deliver these molecules to some
cells and not others and then
when shine light on that network
we can turn on or off that subset
of the cells. If we can turn on
and off a set of cells that's
embedded within within this
dense matrix, we can figure out
how do they contribute to a
behavior. For example, if we
can turn on a set of cells we
can figure out what kinds of
behaviors can it initiate. If we
can turn off a set of cells then
we can delete it momentarily,
and figure out what is necessary
for it. So by being able to dial
in information into cells in the
brain and to delete them we can
to figure out how they contribute
to networks and the behaviors
and diseases that arise from
brain computations. We can hunt
down the exact set of cells that
are contributing to a specific
disease state. Or, which, when
activated or shut down, will
remedy that disease state.
That's very important because
right now a lot of drugs are
developed that target molecules.
But molecules are found
throughout the brain. And, in
fact many cells in the brain
might be very molecularly similar
to one another. If we can target
circuits in the brain, we might
be able to develop much more
specific drugs. Imagine if we
could hunt down the exact set
cells in the brain that when
activated, remedy a brain disorder.
And then if we can go in and look
at the exact molecules in those
cells, maybe we can find drugs
that are much more specific
than existing ones. You might
also imagine that we can use
optogenetics to directly control
brain circuits in patients with
brain disorders. Electricity is
used to stimulate the brain
in deep brain stimulation, if
instead we can actually aim
light at certain cells and turn
them on or off, we might be
much more specific. Rather
than using electricity to turn
on or off the cells in the brain
and have many kinds of cells
activated - the ones we want as
well as their neighbors. If we
could make just one disease
associated subset, associate
with light and we can turn them
on or off we might be able to
treat them with much more
specificity.
So far optogenetics has had
a lot of impact in the scientific
world. But it hasn't been used
in any human patients yet. There
are a couple reasons why. One
is that it requires a gene
therapy to deliver the gene
that encodes for these light
activated molecules into the
body. Currently in the U.S.
there are no FDA approved gene
therapies. In Europe there's
just one. Another issue is that
these molecules come from
organisms like algae and bacteria.
And so if we are putting these
molecules into the body would
they be detected as foreign
agents and attacked by the
immune system, for example.
What we need is a paradigm shift
in how we think about treating
brain disorders. And one of our
major stances is that we need
new technologies if we really
want to either understand the
principles of treating brain
disorders, you know, hunting
down the exact cells in the
brain that could help us treat
brain disorders, or to develop
new modalities, new forms of
energy, new strategies for
treating brain disorders by
correcting the computations
within the brain.