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Steve Ramirez: My first year of grad school,
I found myself in my bedroom
eating lots of Ben & Jerry's
watching some trashy TV
and maybe, maybe listening to Taylor Swift
I had just gone through a breakup.
(Laughter)
So for the longest time, all I would do
is recall the memory of this person over and over again,
wishing that I could get rid of that gut-wrenching,
visceral "blah" feeling.
Now, as it turns out, I'm a neuroscientist,
so I knew that the memory of that person
and the awful, emotional undertones that color in that memory,
are largely mediated by separate brain systems.
And so I thought, what if we could go into the brain
and edit out that nauseating feeling
but while keeping the memory of that person intact?
Then I realized, maybe that's a little bit lofty for now.
So what if we could start off by going into the brain
and just finding a single memory to begin with?
Could we jump-start that memory back to life,
maybe even play with the contents of that memory?
All that said, there is one person in the entire world right now
that I really hope is not watching this talk.
(Laughter)
So there is a catch. There is a catch.
These ideas probably remind you of "Total Recall,"
"Eternal Sunshine of the Spotless Mind,"
or of "Inception."
But the movie stars that we work with
are the celebrities of the lab.
Xu Liu: Test mice.
(Laughter)
As neuroscientists, we work in the lab with mice
trying to understand how memory works.
And today, we hope to convince you that now
we are actually able to activate a memory in the brain
at the speed of light.
To do this, there's only two simple steps to follow.
First, you find and label a memory in the brain,
and then you activate it with a switch.
As simple as that.
(Laughter)
SR: Are you convinced?
So, turns out finding a memory in the brain isn't all that easy.
XL: Indeed. This is way more difficult than, let's say,
finding a needle in a haystack,
because at least, you know, the needle is still something
you can physically put your fingers on.
But memory is not.
And also, there's way more cells in your brain
than the number of straws in a typical haystack.
So yeah, this task does seem to be daunting.
But luckily, we got help from the brain itself.
It turned out that all we need to do is basically
to let the brain form a memory,
and then the brain will tell us which cells are involved
in that particular memory.
SR: So what was going on in my brain
while I was recalling the memory of an ex?
If you were to just completely ignore human ethics for a second
and slice up my brain right now,
you would see that there was an amazing number
of brain regions that were active while recalling that memory.
Now one brain region that would be robustly active
in particular is called the hippocampus,
which for decades has been implicated in processing
the kinds of memories that we hold near and dear,
which also makes it an ideal target to go into
and to try and find and maybe reactivate a memory.
XL: When you zoom in into the hippocampus,
of course you will see lots of cells,
but we are able to find which cells are involved
in a particular memory,
because whenever a cell is active,
like when it's forming a memory,
it will also leave a footprint that will later allow us to know
these cells are recently active.
SR: So the same way that building lights at night
let you know that somebody's probably working there at any given moment,
in a very real sense, there are biological sensors
within a cell that are turned on
only when that cell was just working.
They're sort of biological windows that light up
to let us know that that cell was just active.
XL: So we clipped part of this sensor,
and attached that to a switch to control the cells,
and we packed this switch into an engineered virus
and injected that into the brain of the mice.
So whenever a memory is being formed,
any active cells for that memory
will also have this switch installed.
SR: So here is what the hippocampus looks like
after forming a fear memory, for example.
The sea of blue that you see here
are densely packed brain cells,
but the green brain cells,
the green brain cells are the ones that are holding on
to a specific fear memory.
So you are looking at the crystallization
of the fleeting formation of fear.
You're actually looking at the cross-section of a memory right now.
XL: Now, for the switch we have been talking about,
ideally, the switch has to act really fast.
It shouldn't take minutes or hours to work.
It should act at the speed of the brain, in milliseconds.
SR: So what do you think, Xu?
Could we use, let's say, pharmacological drugs
to activate or inactivate brain cells?
XL: Nah. Drugs are pretty messy. They spread everywhere.
And also it takes them forever to act on cells.
So it will not allow us to control a memory in real time.
So Steve, how about let's zap the brain with electricity?
SR: So electricity is pretty fast,
but we probably wouldn't be able to target it
to just the specific cells that hold onto a memory,
and we'd probably fry the brain.
XL: Oh. That's true. So it looks like, hmm,
indeed we need to find a better way
to impact the brain at the speed of light.
SR: So it just so happens that light travels at the speed of light.
So maybe we could activate or inactive memories
by just using light --
XL: That's pretty fast.
SR: -- and because normally brain cells
don't respond to pulses of light,
so those that would respond to pulses of light
are those that contain a light-sensitive switch.
Now to do that, first we need to trick brain cells
to respond to laser beams.
XL: Yep. You heard it right.
We are trying to shoot lasers into the brain.
(Laughter)
SR: And the technique that lets us do that is optogenetics.
Optogenetics gave us this light switch that we can use
to turn brain cells on or off,
and the name of that switch is channelrhodopsin,
seen here as these green dots attached to this brain cell.
You can think of channelrhodopsin as a sort of light-sensitive switch
that can be artificially installed in brain cells
so that now we can use that switch
to activate or inactivate the brain cell simply by clicking it,
and in this case we click it on with pulses of light.
XL: So we attach this light-sensitive switch of channelrhodopsin
to the sensor we've been talking about
and inject this into the brain.
So whenever a memory is being formed,
any active cell for that particular memory
will also have this light-sensitive switch installed in it
so that we can control these cells
by the flipping of a laser just like this one you see.
SR: So let's put all of this to the test now.
What we can do is we can take our mice
and then we can put them in a box that looks exactly like this box here,
and then we can give them a very mild foot shock
so that they form a fear memory of this box.
They learn that something bad happened here.
Now with our system, the cells that are active
in the hippocampus in the making of this memory,
only those cells will now contain channelrhodopsin.
XL: When you are as small as a mouse,
it feels as if the whole world is trying to get you.
So your best response of defense
is trying to be undetected.
Whenever a mouse is in fear,
it will show this very typical behavior
by staying at one corner of the box,
trying to not move any part of its body,
and this posture is called freezing.
So if a mouse remembers that something bad happened in this box,
and when we put them back into the same box,
it will basically show freezing