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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

  • because it doesn't want to be detected

  • by any potential threats in this box.

  • SR: So you can think of freezing as,

  • you're walking down the street minding your own business,

  • and then out of nowhere you almost run into

  • an ex-girlfriend or ex-boyfriend,

  • and now those terrifying two seconds

  • where you start thinking, "What do I do? Do I say hi?

  • Do I shake their hand? Do I turn around and run away?

  • Do I sit here and pretend like I don't exist?"

  • Those kinds of fleeting thoughts that physically incapacitate you,

  • that temporarily give you that deer-in-headlights look.

  • XL: However, if you put the mouse in a completely different

  • new box, like the next one,

  • it will not be afraid of this box

  • because there's no reason that it will be afraid of this new environment.

  • But what if we put the mouse in this new box

  • but at the same time, we activate the fear memory

  • using lasers just like we did before?

  • Are we going to bring back the fear memory

  • for the first box into this completely new environment?

  • SR: All right, and here's the million-dollar experiment.

  • Now to bring back to life the memory of that day,

  • I remember that the Red Sox had just won,

  • it was a green spring day,

  • perfect for going up and down the river

  • and then maybe going to the North End

  • to get some cannolis, #justsaying.

  • Now Xu and I, on the other hand,

  • were in a completely windowless black room

  • not making any ocular movement that even remotely resembles an eye blink

  • because our eyes were fixed onto a computer screen.

  • We were looking at this mouse here trying to activate a memory

  • for the first time using our technique.

  • XL: And this is what we saw.

  • When we first put the mouse into this box,

  • it's exploring, sniffing around, walking around,

  • minding its own business,

  • because actually by nature,

  • mice are pretty curious animals.

  • They want to know, what's going on in this new box?

  • It's interesting.

  • But the moment we turned on the laser, like you see now,

  • all of a sudden the mouse entered this freezing mode.

  • It stayed here and tried not to move any part of its body.

  • Clearly it's freezing.

  • So indeed, it looks like we are able to bring back

  • the fear memory for the first box

  • in this completely new environment.

  • While watching this, Steve and I

  • are as shocked as the mouse itself.

  • (Laughter)

  • So after the experiment, the two of us just left the room

  • without saying anything.

  • After a kind of long, awkward period of time,

  • Steve broke the silence.

  • SR: "Did that just work?"

  • XL: "Yes," I said. "Indeed it worked!"

  • We're really excited about this.

  • And then we published our findings

  • in the journal Nature.

  • Ever since the publication of our work,

  • we've been receiving numerous comments

  • from all over the Internet.

  • Maybe we can take a look at some of those.

  • ["OMGGGGG FINALLY... so much more to come, virtual reality, neural manipulation, visual dream emulation... neural coding, 'writing and re-writing of memories', mental illnesses. Ahhh the future is awesome"]

  • SR: So the first thing that you'll notice is that people

  • have really strong opinions about this kind of work.

  • Now I happen to completely agree with the optimism

  • of this first quote,