[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.00,0:00:01.00,Default,,0000,0000,0000,,Steve Ramirez: My first year of grad school,
Dialogue: 0,0:00:01.00,0:00:03.00,Default,,0000,0000,0000,,I found myself in my bedroom
Dialogue: 0,0:00:03.00,0:00:06.00,Default,,0000,0000,0000,,eating lots of Ben & Jerry's
Dialogue: 0,0:00:06.00,0:00:07.00,Default,,0000,0000,0000,,watching some trashy TV
Dialogue: 0,0:00:07.00,0:00:11.00,Default,,0000,0000,0000,,and maybe, maybe listening to Taylor Swift.
Dialogue: 0,0:00:11.00,0:00:12.00,Default,,0000,0000,0000,,I had just gone through a breakup.
Dialogue: 0,0:00:12.00,0:00:14.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:00:14.00,0:00:16.00,Default,,0000,0000,0000,,So for the longest time, all I would do
Dialogue: 0,0:00:16.00,0:00:20.00,Default,,0000,0000,0000,,is recall the memory of this person over and over again,
Dialogue: 0,0:00:20.00,0:00:22.00,Default,,0000,0000,0000,,wishing that I could get rid of that gut-wrenching,
Dialogue: 0,0:00:22.00,0:00:25.00,Default,,0000,0000,0000,,visceral "blah" feeling.
Dialogue: 0,0:00:25.00,0:00:27.00,Default,,0000,0000,0000,,Now, as it turns out, I'm a neuroscientist,
Dialogue: 0,0:00:27.00,0:00:30.00,Default,,0000,0000,0000,,so I knew that the memory of that person
Dialogue: 0,0:00:30.00,0:00:33.00,Default,,0000,0000,0000,,and the awful, emotional undertones that color in that memory,
Dialogue: 0,0:00:33.00,0:00:35.00,Default,,0000,0000,0000,,are largely mediated by separate brain systems.
Dialogue: 0,0:00:35.00,0:00:38.00,Default,,0000,0000,0000,,And so I thought, what if we could go into the brain
Dialogue: 0,0:00:38.00,0:00:40.00,Default,,0000,0000,0000,,and edit out that nauseating feeling
Dialogue: 0,0:00:40.00,0:00:43.00,Default,,0000,0000,0000,,but while keeping the memory of that person intact?
Dialogue: 0,0:00:43.00,0:00:45.00,Default,,0000,0000,0000,,Then I realized, maybe that's a little bit lofty for now.
Dialogue: 0,0:00:45.00,0:00:48.00,Default,,0000,0000,0000,,So what if we could start off by going into the brain
Dialogue: 0,0:00:48.00,0:00:51.00,Default,,0000,0000,0000,,and just finding a single memory to begin with?
Dialogue: 0,0:00:51.00,0:00:53.00,Default,,0000,0000,0000,,Could we jump-start that memory back to life,
Dialogue: 0,0:00:53.00,0:00:57.00,Default,,0000,0000,0000,,maybe even play with the contents of that memory?
Dialogue: 0,0:00:57.00,0:00:59.00,Default,,0000,0000,0000,,All that said, there is one person in the entire world right now
Dialogue: 0,0:00:59.00,0:01:01.00,Default,,0000,0000,0000,,that I really hope is not watching this talk.
Dialogue: 0,0:01:01.00,0:01:05.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:01:05.00,0:01:08.00,Default,,0000,0000,0000,,So there is a catch. There is a catch.
Dialogue: 0,0:01:08.00,0:01:11.00,Default,,0000,0000,0000,,These ideas probably remind you of "Total Recall,"
Dialogue: 0,0:01:11.00,0:01:13.00,Default,,0000,0000,0000,,"Eternal Sunshine of the Spotless Mind,"
Dialogue: 0,0:01:13.00,0:01:15.00,Default,,0000,0000,0000,,or of "Inception."
Dialogue: 0,0:01:15.00,0:01:16.00,Default,,0000,0000,0000,,But the movie stars that we work with
Dialogue: 0,0:01:16.00,0:01:18.00,Default,,0000,0000,0000,,are the celebrities of the lab.
Dialogue: 0,0:01:18.00,0:01:20.00,Default,,0000,0000,0000,,Xu Liu: Test mice.
Dialogue: 0,0:01:20.00,0:01:21.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:01:21.00,0:01:24.00,Default,,0000,0000,0000,,As neuroscientists, we work in the lab with mice
Dialogue: 0,0:01:24.00,0:01:28.00,Default,,0000,0000,0000,,trying to understand how memory works.
Dialogue: 0,0:01:28.00,0:01:30.00,Default,,0000,0000,0000,,And today, we hope to convince you that now
Dialogue: 0,0:01:30.00,0:01:33.00,Default,,0000,0000,0000,,we are actually able to activate a memory in the brain
Dialogue: 0,0:01:33.00,0:01:36.00,Default,,0000,0000,0000,,at the speed of light.
Dialogue: 0,0:01:36.00,0:01:39.00,Default,,0000,0000,0000,,To do this, there's only two simple steps to follow.
Dialogue: 0,0:01:39.00,0:01:42.00,Default,,0000,0000,0000,,First, you find and label a memory in the brain,
Dialogue: 0,0:01:42.00,0:01:46.00,Default,,0000,0000,0000,,and then you activate it with a switch.
Dialogue: 0,0:01:46.00,0:01:47.00,Default,,0000,0000,0000,,As simple as that.
Dialogue: 0,0:01:47.00,0:01:49.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:01:49.00,0:01:51.00,Default,,0000,0000,0000,,SR: Are you convinced?
Dialogue: 0,0:01:51.00,0:01:55.00,Default,,0000,0000,0000,,So, turns out finding a memory in the brain isn't all that easy.
Dialogue: 0,0:01:55.00,0:01:57.00,Default,,0000,0000,0000,,XL: Indeed. This is way more difficult than, let's say,
Dialogue: 0,0:01:57.00,0:02:00.00,Default,,0000,0000,0000,,finding a needle in a haystack,
Dialogue: 0,0:02:00.00,0:02:02.00,Default,,0000,0000,0000,,because at least, you know, the needle is still something
Dialogue: 0,0:02:02.00,0:02:05.00,Default,,0000,0000,0000,,you can physically put your fingers on.
Dialogue: 0,0:02:05.00,0:02:07.00,Default,,0000,0000,0000,,But memory is not.
Dialogue: 0,0:02:07.00,0:02:10.00,Default,,0000,0000,0000,,And also, there's way more cells in your brain
Dialogue: 0,0:02:10.00,0:02:15.00,Default,,0000,0000,0000,,than the number of straws in a typical haystack.
Dialogue: 0,0:02:15.00,0:02:18.00,Default,,0000,0000,0000,,So yeah, this task does seem to be daunting.
Dialogue: 0,0:02:18.00,0:02:22.00,Default,,0000,0000,0000,,But luckily, we got help from the brain itself.
Dialogue: 0,0:02:22.00,0:02:24.00,Default,,0000,0000,0000,,It turned out that all we need to do is basically
Dialogue: 0,0:02:24.00,0:02:26.00,Default,,0000,0000,0000,,to let the brain form a memory,
Dialogue: 0,0:02:26.00,0:02:30.00,Default,,0000,0000,0000,,and then the brain will tell us which cells are involved
Dialogue: 0,0:02:30.00,0:02:32.00,Default,,0000,0000,0000,,in that particular memory.
Dialogue: 0,0:02:32.00,0:02:34.00,Default,,0000,0000,0000,,SR: So what was going on in my brain
Dialogue: 0,0:02:34.00,0:02:36.00,Default,,0000,0000,0000,,while I was recalling the memory of an ex?
Dialogue: 0,0:02:36.00,0:02:39.00,Default,,0000,0000,0000,,If you were to just completely ignore human ethics for a second
Dialogue: 0,0:02:39.00,0:02:40.00,Default,,0000,0000,0000,,and slice up my brain right now,
Dialogue: 0,0:02:40.00,0:02:42.00,Default,,0000,0000,0000,,you would see that there was an amazing number
Dialogue: 0,0:02:42.00,0:02:45.00,Default,,0000,0000,0000,,of brain regions that were active while recalling that memory.
Dialogue: 0,0:02:45.00,0:02:48.00,Default,,0000,0000,0000,,Now one brain region that would be robustly active
Dialogue: 0,0:02:48.00,0:02:50.00,Default,,0000,0000,0000,,in particular is called the hippocampus,
Dialogue: 0,0:02:50.00,0:02:53.00,Default,,0000,0000,0000,,which for decades has been implicated in processing
Dialogue: 0,0:02:53.00,0:02:55.00,Default,,0000,0000,0000,,the kinds of memories that we hold near and dear,
Dialogue: 0,0:02:55.00,0:02:58.00,Default,,0000,0000,0000,,which also makes it an ideal target to go into
Dialogue: 0,0:02:58.00,0:03:01.00,Default,,0000,0000,0000,,and to try and find and maybe reactivate a memory.
Dialogue: 0,0:03:01.00,0:03:03.00,Default,,0000,0000,0000,,XL: When you zoom in into the hippocampus,
Dialogue: 0,0:03:03.00,0:03:05.00,Default,,0000,0000,0000,,of course you will see lots of cells,
Dialogue: 0,0:03:05.00,0:03:08.00,Default,,0000,0000,0000,,but we are able to find which cells are involved
Dialogue: 0,0:03:08.00,0:03:10.00,Default,,0000,0000,0000,,in a particular memory,
Dialogue: 0,0:03:10.00,0:03:12.00,Default,,0000,0000,0000,,because whenever a cell is active,
Dialogue: 0,0:03:12.00,0:03:14.00,Default,,0000,0000,0000,,like when it's forming a memory,
Dialogue: 0,0:03:14.00,0:03:18.00,Default,,0000,0000,0000,,it will also leave a footprint that will later allow us to know
Dialogue: 0,0:03:18.00,0:03:20.00,Default,,0000,0000,0000,,these cells are recently active.
Dialogue: 0,0:03:20.00,0:03:22.00,Default,,0000,0000,0000,,SR: So the same way that building lights at night
Dialogue: 0,0:03:22.00,0:03:25.00,Default,,0000,0000,0000,,let you know that somebody's probably working there at any given moment,
Dialogue: 0,0:03:25.00,0:03:29.00,Default,,0000,0000,0000,,in a very real sense, there are biological sensors
Dialogue: 0,0:03:29.00,0:03:31.00,Default,,0000,0000,0000,,within a cell that are turned on
Dialogue: 0,0:03:31.00,0:03:33.00,Default,,0000,0000,0000,,only when that cell was just working.
Dialogue: 0,0:03:33.00,0:03:35.00,Default,,0000,0000,0000,,They're sort of biological windows that light up
Dialogue: 0,0:03:35.00,0:03:37.00,Default,,0000,0000,0000,,to let us know that that cell was just active.
Dialogue: 0,0:03:37.00,0:03:39.00,Default,,0000,0000,0000,,XL: So we clipped part of this sensor,
Dialogue: 0,0:03:39.00,0:03:43.00,Default,,0000,0000,0000,,and attached that to a switch to control the cells,
Dialogue: 0,0:03:43.00,0:03:47.00,Default,,0000,0000,0000,,and we packed this switch into an engineered virus
Dialogue: 0,0:03:47.00,0:03:49.00,Default,,0000,0000,0000,,and injected that into the brain of the mice.
Dialogue: 0,0:03:49.00,0:03:52.00,Default,,0000,0000,0000,,So whenever a memory is being formed,
Dialogue: 0,0:03:52.00,0:03:54.00,Default,,0000,0000,0000,,any active cells for that memory
Dialogue: 0,0:03:54.00,0:03:57.00,Default,,0000,0000,0000,,will also have this switch installed.
Dialogue: 0,0:03:57.00,0:03:58.00,Default,,0000,0000,0000,,SR: So here is what the hippocampus looks like
Dialogue: 0,0:03:58.00,0:04:01.00,Default,,0000,0000,0000,,after forming a fear memory, for example.
Dialogue: 0,0:04:01.00,0:04:03.00,Default,,0000,0000,0000,,The sea of blue that you see here
Dialogue: 0,0:04:03.00,0:04:05.00,Default,,0000,0000,0000,,are densely packed brain cells,
Dialogue: 0,0:04:05.00,0:04:07.00,Default,,0000,0000,0000,,but the green brain cells,
Dialogue: 0,0:04:07.00,0:04:09.00,Default,,0000,0000,0000,,the green brain cells are the ones that are holding on
Dialogue: 0,0:04:09.00,0:04:11.00,Default,,0000,0000,0000,,to a specific fear memory.
Dialogue: 0,0:04:11.00,0:04:13.00,Default,,0000,0000,0000,,So you are looking at the crystallization
Dialogue: 0,0:04:13.00,0:04:15.00,Default,,0000,0000,0000,,of the fleeting formation of fear.
Dialogue: 0,0:04:15.00,0:04:19.00,Default,,0000,0000,0000,,You're actually looking at the cross-section of a memory right now.
Dialogue: 0,0:04:19.00,0:04:21.00,Default,,0000,0000,0000,,XL: Now, for the switch we have been talking about,
Dialogue: 0,0:04:21.00,0:04:24.00,Default,,0000,0000,0000,,ideally, the switch has to act really fast.
Dialogue: 0,0:04:24.00,0:04:27.00,Default,,0000,0000,0000,,It shouldn't take minutes or hours to work.
Dialogue: 0,0:04:27.00,0:04:31.00,Default,,0000,0000,0000,,It should act at the speed of the brain, in milliseconds.
Dialogue: 0,0:04:31.00,0:04:32.00,Default,,0000,0000,0000,,SR: So what do you think, Xu?
Dialogue: 0,0:04:32.00,0:04:35.00,Default,,0000,0000,0000,,Could we use, let's say, pharmacological drugs
Dialogue: 0,0:04:35.00,0:04:37.00,Default,,0000,0000,0000,,to activate or inactivate brain cells?
Dialogue: 0,0:04:37.00,0:04:41.00,Default,,0000,0000,0000,,XL: Nah. Drugs are pretty messy. They spread everywhere.
Dialogue: 0,0:04:41.00,0:04:44.00,Default,,0000,0000,0000,,And also it takes them forever to act on cells.
Dialogue: 0,0:04:44.00,0:04:48.00,Default,,0000,0000,0000,,So it will not allow us to control a memory in real time.
Dialogue: 0,0:04:48.00,0:04:52.00,Default,,0000,0000,0000,,So Steve, how about let's zap the brain with electricity?
Dialogue: 0,0:04:52.00,0:04:54.00,Default,,0000,0000,0000,,SR: So electricity is pretty fast,
Dialogue: 0,0:04:54.00,0:04:56.00,Default,,0000,0000,0000,,but we probably wouldn't be able to target it
Dialogue: 0,0:04:56.00,0:04:58.00,Default,,0000,0000,0000,,to just the specific cells that hold onto a memory,
Dialogue: 0,0:04:58.00,0:05:00.00,Default,,0000,0000,0000,,and we'd probably fry the brain.
Dialogue: 0,0:05:00.00,0:05:03.00,Default,,0000,0000,0000,,XL: Oh. That's true. So it looks like, hmm,
Dialogue: 0,0:05:03.00,0:05:06.00,Default,,0000,0000,0000,,indeed we need to find a better way
Dialogue: 0,0:05:06.00,0:05:09.00,Default,,0000,0000,0000,,to impact the brain at the speed of light.
Dialogue: 0,0:05:09.00,0:05:14.00,Default,,0000,0000,0000,,SR: So it just so happens that light travels at the speed of light.
Dialogue: 0,0:05:14.00,0:05:18.00,Default,,0000,0000,0000,,So maybe we could activate or inactive memories
Dialogue: 0,0:05:18.00,0:05:19.00,Default,,0000,0000,0000,,by just using light --
Dialogue: 0,0:05:19.00,0:05:21.00,Default,,0000,0000,0000,,XL: That's pretty fast.
Dialogue: 0,0:05:21.00,0:05:23.00,Default,,0000,0000,0000,,SR: -- and because normally brain cells
Dialogue: 0,0:05:23.00,0:05:24.00,Default,,0000,0000,0000,,don't respond to pulses of light,
Dialogue: 0,0:05:24.00,0:05:26.00,Default,,0000,0000,0000,,so those that would respond to pulses of light
Dialogue: 0,0:05:26.00,0:05:29.00,Default,,0000,0000,0000,,are those that contain a light-sensitive switch.
Dialogue: 0,0:05:29.00,0:05:31.00,Default,,0000,0000,0000,,Now to do that, first we need to trick brain cells
Dialogue: 0,0:05:31.00,0:05:32.00,Default,,0000,0000,0000,,to respond to laser beams.
Dialogue: 0,0:05:32.00,0:05:33.00,Default,,0000,0000,0000,,XL: Yep. You heard it right.
Dialogue: 0,0:05:33.00,0:05:35.00,Default,,0000,0000,0000,,We are trying to shoot lasers into the brain.
Dialogue: 0,0:05:35.00,0:05:37.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:05:37.00,0:05:40.00,Default,,0000,0000,0000,,SR: And the technique that lets us do that is optogenetics.
Dialogue: 0,0:05:40.00,0:05:44.00,Default,,0000,0000,0000,,Optogenetics gave us this light switch that we can use
Dialogue: 0,0:05:44.00,0:05:45.00,Default,,0000,0000,0000,,to turn brain cells on or off,
Dialogue: 0,0:05:45.00,0:05:48.00,Default,,0000,0000,0000,,and the name of that switch is channelrhodopsin,
Dialogue: 0,0:05:48.00,0:05:50.00,Default,,0000,0000,0000,,seen here as these green dots attached to this brain cell.
Dialogue: 0,0:05:50.00,0:05:53.00,Default,,0000,0000,0000,,You can think of channelrhodopsin as a sort of light-sensitive switch
Dialogue: 0,0:05:53.00,0:05:56.00,Default,,0000,0000,0000,,that can be artificially installed in brain cells
Dialogue: 0,0:05:56.00,0:05:58.00,Default,,0000,0000,0000,,so that now we can use that switch
Dialogue: 0,0:05:58.00,0:06:01.00,Default,,0000,0000,0000,,to activate or inactivate the brain cell simply by clicking it,
Dialogue: 0,0:06:01.00,0:06:03.00,Default,,0000,0000,0000,,and in this case we click it on with pulses of light.
Dialogue: 0,0:06:03.00,0:06:07.00,Default,,0000,0000,0000,,XL: So we attach this light-sensitive switch of channelrhodopsin
Dialogue: 0,0:06:07.00,0:06:09.00,Default,,0000,0000,0000,,to the sensor we've been talking about
Dialogue: 0,0:06:09.00,0:06:12.00,Default,,0000,0000,0000,,and inject this into the brain.
Dialogue: 0,0:06:12.00,0:06:15.00,Default,,0000,0000,0000,,So whenever a memory is being formed,
Dialogue: 0,0:06:15.00,0:06:17.00,Default,,0000,0000,0000,,any active cell for that particular memory
Dialogue: 0,0:06:17.00,0:06:21.00,Default,,0000,0000,0000,,will also have this light-sensitive switch installed in it
Dialogue: 0,0:06:21.00,0:06:23.00,Default,,0000,0000,0000,,so that we can control these cells
Dialogue: 0,0:06:23.00,0:06:27.00,Default,,0000,0000,0000,,by the flipping of a laser just like this one you see.
Dialogue: 0,0:06:27.00,0:06:30.00,Default,,0000,0000,0000,,SR: So let's put all of this to the test now.
Dialogue: 0,0:06:30.00,0:06:32.00,Default,,0000,0000,0000,,What we can do is we can take our mice
Dialogue: 0,0:06:32.00,0:06:35.00,Default,,0000,0000,0000,,and then we can put them in a box that looks exactly like this box here,
Dialogue: 0,0:06:35.00,0:06:38.00,Default,,0000,0000,0000,,and then we can give them a very mild foot shock
Dialogue: 0,0:06:38.00,0:06:40.00,Default,,0000,0000,0000,,so that they form a fear memory of this box.
Dialogue: 0,0:06:40.00,0:06:42.00,Default,,0000,0000,0000,,They learn that something bad happened here.
Dialogue: 0,0:06:42.00,0:06:44.00,Default,,0000,0000,0000,,Now with our system, the cells that are active
Dialogue: 0,0:06:44.00,0:06:47.00,Default,,0000,0000,0000,,in the hippocampus in the making of this memory,
Dialogue: 0,0:06:47.00,0:06:50.00,Default,,0000,0000,0000,,only those cells will now contain channelrhodopsin.
Dialogue: 0,0:06:50.00,0:06:53.00,Default,,0000,0000,0000,,XL: When you are as small as a mouse,
Dialogue: 0,0:06:53.00,0:06:56.00,Default,,0000,0000,0000,,it feels as if the whole world is trying to get you.
Dialogue: 0,0:06:56.00,0:06:58.00,Default,,0000,0000,0000,,So your best response of defense
Dialogue: 0,0:06:58.00,0:07:01.00,Default,,0000,0000,0000,,is trying to be undetected.
Dialogue: 0,0:07:01.00,0:07:03.00,Default,,0000,0000,0000,,Whenever a mouse is in fear,
Dialogue: 0,0:07:03.00,0:07:04.00,Default,,0000,0000,0000,,it will show this very typical behavior
Dialogue: 0,0:07:04.00,0:07:06.00,Default,,0000,0000,0000,,by staying at one corner of the box,
Dialogue: 0,0:07:06.00,0:07:09.00,Default,,0000,0000,0000,,trying to not move any part of its body,
Dialogue: 0,0:07:09.00,0:07:12.00,Default,,0000,0000,0000,,and this posture is called freezing.
Dialogue: 0,0:07:12.00,0:07:17.00,Default,,0000,0000,0000,,So if a mouse remembers that something bad happened in this box,
Dialogue: 0,0:07:17.00,0:07:19.00,Default,,0000,0000,0000,,and when we put them back into the same box,
Dialogue: 0,0:07:19.00,0:07:21.00,Default,,0000,0000,0000,,it will basically show freezing
Dialogue: 0,0:07:21.00,0:07:23.00,Default,,0000,0000,0000,,because it doesn't want to be detected
Dialogue: 0,0:07:23.00,0:07:26.00,Default,,0000,0000,0000,,by any potential threats in this box.
Dialogue: 0,0:07:26.00,0:07:28.00,Default,,0000,0000,0000,,SR: So you can think of freezing as,
Dialogue: 0,0:07:28.00,0:07:30.00,Default,,0000,0000,0000,,you're walking down the street minding your own business,
Dialogue: 0,0:07:30.00,0:07:31.00,Default,,0000,0000,0000,,and then out of nowhere you almost run into
Dialogue: 0,0:07:31.00,0:07:34.00,Default,,0000,0000,0000,,an ex-girlfriend or ex-boyfriend,
Dialogue: 0,0:07:34.00,0:07:36.00,Default,,0000,0000,0000,,and now those terrifying two seconds
Dialogue: 0,0:07:36.00,0:07:38.00,Default,,0000,0000,0000,,where you start thinking, "What do I do? Do I say hi?
Dialogue: 0,0:07:38.00,0:07:39.00,Default,,0000,0000,0000,,Do I shake their hand? Do I turn around and run away?
Dialogue: 0,0:07:39.00,0:07:41.00,Default,,0000,0000,0000,,Do I sit here and pretend like I don't exist?"
Dialogue: 0,0:07:41.00,0:07:44.00,Default,,0000,0000,0000,,Those kinds of fleeting thoughts that physically incapacitate you,
Dialogue: 0,0:07:44.00,0:07:47.00,Default,,0000,0000,0000,,that temporarily give you that deer-in-headlights look.
Dialogue: 0,0:07:47.00,0:07:50.00,Default,,0000,0000,0000,,XL: However, if you put the mouse in a completely different
Dialogue: 0,0:07:50.00,0:07:53.00,Default,,0000,0000,0000,,new box, like the next one,
Dialogue: 0,0:07:53.00,0:07:56.00,Default,,0000,0000,0000,,it will not be afraid of this box
Dialogue: 0,0:07:56.00,0:08:00.00,Default,,0000,0000,0000,,because there's no reason that it will be afraid of this new environment.
Dialogue: 0,0:08:00.00,0:08:03.00,Default,,0000,0000,0000,,But what if we put the mouse in this new box
Dialogue: 0,0:08:03.00,0:08:07.00,Default,,0000,0000,0000,,but at the same time, we activate the fear memory
Dialogue: 0,0:08:07.00,0:08:10.00,Default,,0000,0000,0000,,using lasers just like we did before?
Dialogue: 0,0:08:10.00,0:08:13.00,Default,,0000,0000,0000,,Are we going to bring back the fear memory
Dialogue: 0,0:08:13.00,0:08:17.00,Default,,0000,0000,0000,,for the first box into this completely new environment?
Dialogue: 0,0:08:17.00,0:08:19.00,Default,,0000,0000,0000,,SR: All right, and here's the million-dollar experiment.
Dialogue: 0,0:08:19.00,0:08:22.00,Default,,0000,0000,0000,,Now to bring back to life the memory of that day,
Dialogue: 0,0:08:22.00,0:08:24.00,Default,,0000,0000,0000,,I remember that the Red Sox had just won,
Dialogue: 0,0:08:24.00,0:08:26.00,Default,,0000,0000,0000,,it was a green spring day,
Dialogue: 0,0:08:26.00,0:08:28.00,Default,,0000,0000,0000,,perfect for going up and down the river
Dialogue: 0,0:08:28.00,0:08:31.00,Default,,0000,0000,0000,,and then maybe going to the North End
Dialogue: 0,0:08:31.00,0:08:33.00,Default,,0000,0000,0000,,to get some cannolis, #justsaying.
Dialogue: 0,0:08:33.00,0:08:36.00,Default,,0000,0000,0000,,Now Xu and I, on the other hand,
Dialogue: 0,0:08:36.00,0:08:39.00,Default,,0000,0000,0000,,were in a completely windowless black room
Dialogue: 0,0:08:39.00,0:08:42.00,Default,,0000,0000,0000,,not making any ocular movement that even remotely resembles an eye blink
Dialogue: 0,0:08:42.00,0:08:45.00,Default,,0000,0000,0000,,because our eyes were fixed onto a computer screen.
Dialogue: 0,0:08:45.00,0:08:47.00,Default,,0000,0000,0000,,We were looking at this mouse here trying to activate a memory
Dialogue: 0,0:08:47.00,0:08:49.00,Default,,0000,0000,0000,,for the first time using our technique.
Dialogue: 0,0:08:49.00,0:08:52.00,Default,,0000,0000,0000,,XL: And this is what we saw.
Dialogue: 0,0:08:52.00,0:08:54.00,Default,,0000,0000,0000,,When we first put the mouse into this box,
Dialogue: 0,0:08:54.00,0:08:57.00,Default,,0000,0000,0000,,it's exploring, sniffing around, walking around,
Dialogue: 0,0:08:57.00,0:08:59.00,Default,,0000,0000,0000,,minding its own business,
Dialogue: 0,0:08:59.00,0:09:01.00,Default,,0000,0000,0000,,because actually by nature,
Dialogue: 0,0:09:01.00,0:09:03.00,Default,,0000,0000,0000,,mice are pretty curious animals.
Dialogue: 0,0:09:03.00,0:09:05.00,Default,,0000,0000,0000,,They want to know, what's going on in this new box?
Dialogue: 0,0:09:05.00,0:09:07.00,Default,,0000,0000,0000,,It's interesting.
Dialogue: 0,0:09:07.00,0:09:10.00,Default,,0000,0000,0000,,But the moment we turned on the laser, like you see now,
Dialogue: 0,0:09:10.00,0:09:13.00,Default,,0000,0000,0000,,all of a sudden the mouse entered this freezing mode.
Dialogue: 0,0:09:13.00,0:09:18.00,Default,,0000,0000,0000,,It stayed here and tried not to move any part of its body.
Dialogue: 0,0:09:18.00,0:09:19.00,Default,,0000,0000,0000,,Clearly it's freezing.
Dialogue: 0,0:09:19.00,0:09:22.00,Default,,0000,0000,0000,,So indeed, it looks like we are able to bring back
Dialogue: 0,0:09:22.00,0:09:24.00,Default,,0000,0000,0000,,the fear memory for the first box
Dialogue: 0,0:09:24.00,0:09:27.00,Default,,0000,0000,0000,,in this completely new environment.
Dialogue: 0,0:09:27.00,0:09:29.00,Default,,0000,0000,0000,,While watching this, Steve and I
Dialogue: 0,0:09:29.00,0:09:32.00,Default,,0000,0000,0000,,are as shocked as the mouse itself.
Dialogue: 0,0:09:32.00,0:09:33.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:09:33.00,0:09:36.00,Default,,0000,0000,0000,,So after the experiment, the two of us just left the room
Dialogue: 0,0:09:36.00,0:09:38.00,Default,,0000,0000,0000,,without saying anything.
Dialogue: 0,0:09:38.00,0:09:41.00,Default,,0000,0000,0000,,After a kind of long, awkward period of time,
Dialogue: 0,0:09:41.00,0:09:43.00,Default,,0000,0000,0000,,Steve broke the silence.
Dialogue: 0,0:09:43.00,0:09:46.00,Default,,0000,0000,0000,,SR: "Did that just work?"
Dialogue: 0,0:09:46.00,0:09:49.00,Default,,0000,0000,0000,,XL: "Yes," I said. "Indeed it worked!"
Dialogue: 0,0:09:49.00,0:09:51.00,Default,,0000,0000,0000,,We're really excited about this.
Dialogue: 0,0:09:51.00,0:09:53.00,Default,,0000,0000,0000,,And then we published our findings
Dialogue: 0,0:09:53.00,0:09:55.00,Default,,0000,0000,0000,,in the journal Nature.
Dialogue: 0,0:09:55.00,0:09:58.00,Default,,0000,0000,0000,,Ever since the publication of our work,
Dialogue: 0,0:09:58.00,0:10:00.00,Default,,0000,0000,0000,,we've been receiving numerous comments
Dialogue: 0,0:10:00.00,0:10:02.00,Default,,0000,0000,0000,,from all over the Internet.
Dialogue: 0,0:10:02.00,0:10:06.00,Default,,0000,0000,0000,,Maybe we can take a look at some of those.
Dialogue: 0,0:10:06.00,0:10:08.00,Default,,0000,0000,0000,,["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"]
Dialogue: 0,0:10:08.00,0:10:10.00,Default,,0000,0000,0000,,SR: So the first thing that you'll notice is that people
Dialogue: 0,0:10:10.00,0:10:13.00,Default,,0000,0000,0000,,have really strong opinions about this kind of work.
Dialogue: 0,0:10:13.00,0:10:16.00,Default,,0000,0000,0000,,Now I happen to completely agree with the optimism
Dialogue: 0,0:10:16.00,0:10:17.00,Default,,0000,0000,0000,,of this first quote,
Dialogue: 0,0:10:17.00,0:10:19.00,Default,,0000,0000,0000,,because on a scale of zero to Morgan Freeman's voice,
Dialogue: 0,0:10:19.00,0:10:22.00,Default,,0000,0000,0000,,it happens to be one of the most evocative accolades
Dialogue: 0,0:10:22.00,0:10:23.00,Default,,0000,0000,0000,,that I've heard come our way.
Dialogue: 0,0:10:23.00,0:10:25.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:10:25.00,0:10:27.00,Default,,0000,0000,0000,,But as you'll see, it's not the only opinion that's out there.
Dialogue: 0,0:10:27.00,0:10:29.00,Default,,0000,0000,0000,,["This scares the hell out of me... What if they could do that easily in humans in a couple of years?! OH MY GOD WE'RE DOOMED"]
Dialogue: 0,0:10:29.00,0:10:31.00,Default,,0000,0000,0000,,XL: Indeed, if we take a look at the second one,
Dialogue: 0,0:10:31.00,0:10:33.00,Default,,0000,0000,0000,,I think we can all agree that it's, meh,
Dialogue: 0,0:10:33.00,0:10:35.00,Default,,0000,0000,0000,,probably not as positive.
Dialogue: 0,0:10:35.00,0:10:37.00,Default,,0000,0000,0000,,But this also reminds us that,
Dialogue: 0,0:10:37.00,0:10:40.00,Default,,0000,0000,0000,,although we are still working with mice,
Dialogue: 0,0:10:40.00,0:10:43.00,Default,,0000,0000,0000,,it's probably a good idea to start thinking and discussing
Dialogue: 0,0:10:43.00,0:10:46.00,Default,,0000,0000,0000,,about the possible ethical ramifications
Dialogue: 0,0:10:46.00,0:10:48.00,Default,,0000,0000,0000,,of memory control.
Dialogue: 0,0:10:48.00,0:10:50.00,Default,,0000,0000,0000,,SR: Now, in the spirit of the third quote,
Dialogue: 0,0:10:50.00,0:10:52.00,Default,,0000,0000,0000,,we want to tell you about a recent project that we've been
Dialogue: 0,0:10:52.00,0:10:55.00,Default,,0000,0000,0000,,working on in lab that we've called Project Inception.
Dialogue: 0,0:10:55.00,0:10:58.00,Default,,0000,0000,0000,,["They should make a movie about this. Where they plant ideas into peoples minds, so they can control them for their own personal gain. We'll call it: Inception."]
Dialogue: 0,0:10:58.00,0:11:02.00,Default,,0000,0000,0000,,So we reasoned that now that we can reactivate a memory,
Dialogue: 0,0:11:02.00,0:11:05.00,Default,,0000,0000,0000,,what if we do so but then begin to tinker with that memory?
Dialogue: 0,0:11:05.00,0:11:08.00,Default,,0000,0000,0000,,Could we possibly even turn it into a false memory?
Dialogue: 0,0:11:08.00,0:11:12.00,Default,,0000,0000,0000,,XL: So all memory is sophisticated and dynamic,
Dialogue: 0,0:11:12.00,0:11:15.00,Default,,0000,0000,0000,,but if just for simplicity, let's imagine memory
Dialogue: 0,0:11:15.00,0:11:16.00,Default,,0000,0000,0000,,as a movie clip.
Dialogue: 0,0:11:16.00,0:11:19.00,Default,,0000,0000,0000,,So far what we've told you is basically we can control
Dialogue: 0,0:11:19.00,0:11:21.00,Default,,0000,0000,0000,,this "play" button of the clip
Dialogue: 0,0:11:21.00,0:11:25.00,Default,,0000,0000,0000,,so that we can play this video clip any time, anywhere.
Dialogue: 0,0:11:25.00,0:11:28.00,Default,,0000,0000,0000,,But is there a possibility that we can actually get
Dialogue: 0,0:11:28.00,0:11:31.00,Default,,0000,0000,0000,,inside the brain and edit this movie clip
Dialogue: 0,0:11:31.00,0:11:34.00,Default,,0000,0000,0000,,so that we can make it different from the original?
Dialogue: 0,0:11:34.00,0:11:36.00,Default,,0000,0000,0000,,Yes we can.
Dialogue: 0,0:11:36.00,0:11:38.00,Default,,0000,0000,0000,,Turned out that all we need to do is basically
Dialogue: 0,0:11:38.00,0:11:42.00,Default,,0000,0000,0000,,reactivate a memory using lasers just like we did before,
Dialogue: 0,0:11:42.00,0:11:46.00,Default,,0000,0000,0000,,but at the same time, if we present new information
Dialogue: 0,0:11:46.00,0:11:50.00,Default,,0000,0000,0000,,and allow this new information to incorporate into this old memory,
Dialogue: 0,0:11:50.00,0:11:52.00,Default,,0000,0000,0000,,this will change the memory.
Dialogue: 0,0:11:52.00,0:11:56.00,Default,,0000,0000,0000,,It's sort of like making a remix tape.
Dialogue: 0,0:11:56.00,0:11:59.00,Default,,0000,0000,0000,,SR: So how do we do this?
Dialogue: 0,0:11:59.00,0:12:01.00,Default,,0000,0000,0000,,Rather than finding a fear memory in the brain,
Dialogue: 0,0:12:01.00,0:12:02.00,Default,,0000,0000,0000,,we can start by taking our animals,
Dialogue: 0,0:12:02.00,0:12:05.00,Default,,0000,0000,0000,,and let's say we put them in a blue box like this blue box here
Dialogue: 0,0:12:05.00,0:12:08.00,Default,,0000,0000,0000,,and we find the brain cells that represent that blue box
Dialogue: 0,0:12:08.00,0:12:10.00,Default,,0000,0000,0000,,and we trick them to respond to pulses of light
Dialogue: 0,0:12:10.00,0:12:12.00,Default,,0000,0000,0000,,exactly like we had said before.
Dialogue: 0,0:12:12.00,0:12:14.00,Default,,0000,0000,0000,,Now the next day, we can take our animals and place them
Dialogue: 0,0:12:14.00,0:12:17.00,Default,,0000,0000,0000,,in a red box that they've never experienced before.
Dialogue: 0,0:12:17.00,0:12:19.00,Default,,0000,0000,0000,,We can shoot light into the brain to reactivate
Dialogue: 0,0:12:19.00,0:12:21.00,Default,,0000,0000,0000,,the memory of the blue box.
Dialogue: 0,0:12:21.00,0:12:23.00,Default,,0000,0000,0000,,So what would happen here if, while the animal
Dialogue: 0,0:12:23.00,0:12:24.00,Default,,0000,0000,0000,,is recalling the memory of the blue box,
Dialogue: 0,0:12:24.00,0:12:27.00,Default,,0000,0000,0000,,we gave it a couple of mild foot shocks?
Dialogue: 0,0:12:27.00,0:12:30.00,Default,,0000,0000,0000,,So here we're trying to artificially make an association
Dialogue: 0,0:12:30.00,0:12:32.00,Default,,0000,0000,0000,,between the memory of the blue box
Dialogue: 0,0:12:32.00,0:12:33.00,Default,,0000,0000,0000,,and the foot shocks themselves.
Dialogue: 0,0:12:33.00,0:12:35.00,Default,,0000,0000,0000,,We're just trying to connect the two.
Dialogue: 0,0:12:35.00,0:12:37.00,Default,,0000,0000,0000,,So to test if we had done so,
Dialogue: 0,0:12:37.00,0:12:38.00,Default,,0000,0000,0000,,we can take our animals once again
Dialogue: 0,0:12:38.00,0:12:40.00,Default,,0000,0000,0000,,and place them back in the blue box.
Dialogue: 0,0:12:40.00,0:12:43.00,Default,,0000,0000,0000,,Again, we had just reactivated the memory of the blue box
Dialogue: 0,0:12:43.00,0:12:45.00,Default,,0000,0000,0000,,while the animal got a couple of mild foot shocks,
Dialogue: 0,0:12:45.00,0:12:47.00,Default,,0000,0000,0000,,and now the animal suddenly freezes.
Dialogue: 0,0:12:47.00,0:12:50.00,Default,,0000,0000,0000,,It's as though it's recalling being mildly shocked in this environment
Dialogue: 0,0:12:50.00,0:12:53.00,Default,,0000,0000,0000,,even though that never actually happened.
Dialogue: 0,0:12:53.00,0:12:55.00,Default,,0000,0000,0000,,So it formed a false memory,
Dialogue: 0,0:12:55.00,0:12:57.00,Default,,0000,0000,0000,,because it's falsely fearing an environment
Dialogue: 0,0:12:57.00,0:12:58.00,Default,,0000,0000,0000,,where, technically speaking,
Dialogue: 0,0:12:58.00,0:13:01.00,Default,,0000,0000,0000,,nothing bad actually happened to it.
Dialogue: 0,0:13:01.00,0:13:03.00,Default,,0000,0000,0000,,XL: So, so far we are only talking about
Dialogue: 0,0:13:03.00,0:13:06.00,Default,,0000,0000,0000,,this light-controlled "on" switch.
Dialogue: 0,0:13:06.00,0:13:09.00,Default,,0000,0000,0000,,In fact, we also have a light-controlled "off" switch,
Dialogue: 0,0:13:09.00,0:13:11.00,Default,,0000,0000,0000,,and it's very easy to imagine that
Dialogue: 0,0:13:11.00,0:13:13.00,Default,,0000,0000,0000,,by installing this light-controlled "off" switch,
Dialogue: 0,0:13:13.00,0:13:19.00,Default,,0000,0000,0000,,we can also turn off a memory, any time, anywhere.
Dialogue: 0,0:13:19.00,0:13:21.00,Default,,0000,0000,0000,,So everything we've been talking about today
Dialogue: 0,0:13:21.00,0:13:26.00,Default,,0000,0000,0000,,is based on this philosophically charged principle of neuroscience
Dialogue: 0,0:13:26.00,0:13:30.00,Default,,0000,0000,0000,,that the mind, with its seemingly mysterious properties,
Dialogue: 0,0:13:30.00,0:13:34.00,Default,,0000,0000,0000,,is actually made of physical stuff that we can tinker with.
Dialogue: 0,0:13:34.00,0:13:35.00,Default,,0000,0000,0000,,SR: And for me personally,
Dialogue: 0,0:13:35.00,0:13:37.00,Default,,0000,0000,0000,,I see a world where we can reactivate
Dialogue: 0,0:13:37.00,0:13:39.00,Default,,0000,0000,0000,,any kind of memory that we'd like.
Dialogue: 0,0:13:39.00,0:13:42.00,Default,,0000,0000,0000,,I also see a world where we can erase unwanted memories.
Dialogue: 0,0:13:42.00,0:13:44.00,Default,,0000,0000,0000,,Now, I even see a world where editing memories
Dialogue: 0,0:13:44.00,0:13:46.00,Default,,0000,0000,0000,,is something of a reality,
Dialogue: 0,0:13:46.00,0:13:47.00,Default,,0000,0000,0000,,because we're living in a time where it's possible
Dialogue: 0,0:13:47.00,0:13:50.00,Default,,0000,0000,0000,,to pluck questions from the tree of science fiction
Dialogue: 0,0:13:50.00,0:13:52.00,Default,,0000,0000,0000,,and to ground them in experimental reality.
Dialogue: 0,0:13:52.00,0:13:54.00,Default,,0000,0000,0000,,XL: Nowadays, people in the lab
Dialogue: 0,0:13:54.00,0:13:56.00,Default,,0000,0000,0000,,and people in other groups all over the world
Dialogue: 0,0:13:56.00,0:14:00.00,Default,,0000,0000,0000,,are using similar methods to activate or edit memories,
Dialogue: 0,0:14:00.00,0:14:04.00,Default,,0000,0000,0000,,whether that's old or new, positive or negative,
Dialogue: 0,0:14:04.00,0:14:07.00,Default,,0000,0000,0000,,all sorts of memories so that we can understand
Dialogue: 0,0:14:07.00,0:14:08.00,Default,,0000,0000,0000,,how memory works.
Dialogue: 0,0:14:08.00,0:14:10.00,Default,,0000,0000,0000,,SR: For example, one group in our lab
Dialogue: 0,0:14:10.00,0:14:13.00,Default,,0000,0000,0000,,was able to find the brain cells that make up a fear memory
Dialogue: 0,0:14:13.00,0:14:16.00,Default,,0000,0000,0000,,and converted them into a pleasurable memory, just like that.
Dialogue: 0,0:14:16.00,0:14:19.00,Default,,0000,0000,0000,,That's exactly what I mean about editing these kinds of processes.
Dialogue: 0,0:14:19.00,0:14:21.00,Default,,0000,0000,0000,,Now one dude in lab was even able to reactivate
Dialogue: 0,0:14:21.00,0:14:23.00,Default,,0000,0000,0000,,memories of female mice in male mice,
Dialogue: 0,0:14:23.00,0:14:26.00,Default,,0000,0000,0000,,which rumor has it is a pleasurable experience.
Dialogue: 0,0:14:26.00,0:14:30.00,Default,,0000,0000,0000,,XL: Indeed, we are living in a very exciting moment
Dialogue: 0,0:14:30.00,0:14:34.00,Default,,0000,0000,0000,,where science doesn't have any arbitrary speed limits
Dialogue: 0,0:14:34.00,0:14:37.00,Default,,0000,0000,0000,,but is only bound by our own imagination.
Dialogue: 0,0:14:37.00,0:14:39.00,Default,,0000,0000,0000,,SR: And finally, what do we make of all this?
Dialogue: 0,0:14:39.00,0:14:41.00,Default,,0000,0000,0000,,How do we push this technology forward?
Dialogue: 0,0:14:41.00,0:14:43.00,Default,,0000,0000,0000,,These are the questions that should not remain
Dialogue: 0,0:14:43.00,0:14:45.00,Default,,0000,0000,0000,,just inside the lab,
Dialogue: 0,0:14:45.00,0:14:47.00,Default,,0000,0000,0000,,and so one goal of today's talk was to bring everybody
Dialogue: 0,0:14:47.00,0:14:50.00,Default,,0000,0000,0000,,up to speed with the kind of stuff that's possible
Dialogue: 0,0:14:50.00,0:14:51.00,Default,,0000,0000,0000,,in modern neuroscience,
Dialogue: 0,0:14:51.00,0:14:53.00,Default,,0000,0000,0000,,but now, just as importantly,
Dialogue: 0,0:14:53.00,0:14:56.00,Default,,0000,0000,0000,,to actively engage everybody in this conversation.
Dialogue: 0,0:14:56.00,0:14:58.00,Default,,0000,0000,0000,,So let's think together as a team about what this all means
Dialogue: 0,0:14:58.00,0:15:01.00,Default,,0000,0000,0000,,and where we can and should go from here,
Dialogue: 0,0:15:01.00,0:15:03.00,Default,,0000,0000,0000,,because Xu and I think we all have
Dialogue: 0,0:15:03.00,0:15:05.00,Default,,0000,0000,0000,,some really big decisions ahead of us.
Dialogue: 0,0:15:05.00,0:15:06.00,Default,,0000,0000,0000,,Thank you.\NXL: Thank you.
Dialogue: 0,0:15:06.00,0:15:08.00,Default,,0000,0000,0000,,(Applause)