SteveRamirez_2013X[史蒂夫.拉米雷斯_刘旭][老鼠_雷射光束和被操控的记忆].pdf
www.XiYuS锡育软件Steve Ramirez:My first year of grad school,I found myself inmy bedroom eating lots of Ben&Jerrys watching sometrashy TV and maybe,maybe listening to Taylor Swift.史蒂夫拉米雷斯:就读研究生的第一年,我常常待在自己的卧室里,大吃Ben&Jerrys 冰淇淋,看看一些没营养的电视节目,或许,或许还听听泰勒斯威夫特的歌。00:12I had just gone through a breakup.我刚刚经历一场失恋嘛。00:23(Laughter)So for the longest time,all I would do is recall thememory of this person over and over again,wishing that Icould get rid of that gut-wrenching,visceral blah feeling.(笑声)所以很长一段时间里,我所做的 就是一边反反复复地回忆有关我前任恋人的一切,一边希望自己能摆脱那种 令人五脏都纠结的痛楚。00:24Now,as it turns out,Im a neuroscientist,so I knew that thememory of that person and the awful,emotional undertonesthat color in that memory,are largely mediated by separatebrain systems.现在,我成为了一名神经科学家,我也知道了有关那个人的记忆,以及那记忆中所挟带的痛苦情感,其实很大程度上是由不同脑区调控的。00:37And so I thought,what if we could go into the brain and editout that nauseating feeling but while keeping the memoryof that person intact?所以我就想:我们是不是能深入到人们的大脑中,仅仅剔除那种令人食不下咽的痛苦 却同时完好地保留关于那个前任恋人的记忆?00:47Then I realized,maybe thats a little bit lofty for now.然后我意识到也许这个想法对现在来说 或许还是有些不切实际。00:55grad:n.毕业生;校友 trashy:adj.没用的;碎屑的;垃圾似的;无价值的 over and over again:adv.一再地;反复不断地 gut-wrenching:adj.极度痛苦的,撕心裂肺的 visceral:adj.内脏的;出于本能的;发自肺腑的;粗俗的 blah:n.废话;空话;瞎说/int.废话 undertones:n.低音;浅色;小声;潜在的含意 mediated:vt.仲裁,调停;调解(mediate的过去式及过去分词形式)nauseating:adj.令人恶心的;厌恶的/v.使恶心(nauseate的ing形式)lofty:adj.高的;崇高的;高级的;高傲的/So what if we could start off by going into the brain and justfinding a single memory to begin with?那么我们是不是可以先从在大脑中 找出一个单一记忆开始着手做起呢?00:57Could we jump-start that memory back to life,maybe evenplay with the contents of that memory?我们是否可以跳转到一段过往记忆并在 现实中重新演绎,甚至也许可以稍稍改编一下记忆的内容?01:03All that said,there is one person in the entire world right nowthat I really hope is not watching this talk.不过现在,全世界有一个人,我倒是希望她 现在没看到这段演讲。01:09(Laughter)So there is a catch.There is a catch.(笑声)所以啦,凡事都有代价。01:13These ideas probably remind you of Total Recall,也许以上这些设想会让你想起全面回忆、01:20Eternal Sunshine of the Spotless Mind,暖暖内含光、01:23or of Inception.或者盗梦空间这些电影。01:25But the movie stars that we work with are the celebrities ofthe lab.但是和我们研究人员合作的 电影明星 却都是实验室的大牌。01:27Xu Liu:Test mice.刘旭:(也就是)试验鼠。01:30(Laughter)As neuroscientists,we work in the lab with micetrying to understand how memory works.(笑声)作为神经科学家,我们通过研究老鼠,来尝试理解记忆的运作,01:32And today,we hope to convince you that now we are actuallyable to activate a memory in the brain at the speed of light.今天,我们希望向你们证明 我们事实上能够在大脑中 快速激活一段记忆。01:40start off:出发,开始 begin with:以开始;开始于 jump-start:vt.起动;发动/n.助动启动 Eternal:adj.永恒的;不朽的Spotless:adj.无可挑剔的;无瑕疵的;纯洁的 Inception:n.起初;获得学位/n.盗梦空间(电影名)celebrities:n.名人(celebrity的复数);名誉 activate:vt.刺激;使活动;使活泼;使产生放射性/vi.激活;有活力To do this,theres only two simple steps to follow.要完成这个任务,我们只需要两个简单的步骤。01:48First,you find and label a memory in the brain,and then youactivate it with a switch.首先,在大脑中找到并且标记一段记忆,然后用开关激活它。01:51As simple as that.就是这么简单。01:58(Laughter)SR:Are you convinced?(笑声)史蒂夫:你们信服了吗?01:59So,turns out finding a memory in the brain isnt all that easy.其实,在大脑中找到一段记忆并非如此简单。02:03XL:Indeed.This is way more difficult than,lets say,finding aneedle in a haystack,because at least,you know,the needleis still something you can physically put your fingers on.刘旭:确实。这其实要比 在稻草堆中找到一根针要难得多,因为至少,针还是一个 你能确实触摸到的实物。02:07TED演讲者:Steve Ramirez and Xu Li|史蒂夫.拉米雷斯,刘旭演讲标题:A mouse.A laser beam.A manipulated memory.|老鼠,雷射光束和被操控的记忆内容概要:After studying how to generate a fruit fly able to learn much faster than normal,XuLiu.s latest work investigates how to activate and deactivate specific memories in mice.我们能够改编记忆吗?这个带有科幻色彩的问题就是史蒂夫.拉米雷斯和刘旭在麻省理工学院实验室里要求证的问题。最后这对搭档向一只活老鼠发射了一道雷射光,从而激活并控制了它的记忆。在这场幽默的演讲中,两位科学家不仅分享了他们是如何做得到的,更重要的是他们为何而做。(录制于TEDx波士顿)But memory is not.但记忆不是。02:17And also,theres way more cells in your brain than thenumber of straws in a typical haystack.并且,大脑中的脑细胞可比 稻草堆中的稻谷要多得多。02:19So yeah,this task does seem to be daunting.所以,这个任务似乎异常艰难。02:27But luckily,we got help from the brain itself.但幸运的是,我们从大脑自身得到了帮助。02:30It turned out that all we need to do is basically to let thebrain form a memory,and then the brain will tell us whichcells are involved in that particular memory.事实上我们只需要 让大脑自己生成一段记忆,然后大脑会告诉我们哪些脑细胞 参与了这一段记忆的组成。02:34haystack:n.干草堆/比喻如大海捞针般难找 straws:n.作物稻草;吸管(straw的复数形式)daunting:adj.使人畏缩的;使人气馁的;令人怯步的SR:So what was going on in my brain while I was recallingthe memory of an ex?史蒂夫:那么在我回忆前任恋人的时候,我的大脑中究竟发生了什么呢?02:44If you were to just completely ignore human ethics for asecond and slice up my brain right now,you would see thatthere was an amazing number of brain regions that wereactive while recalling that memory.如果你们能暂且抛开人类道德,即刻将我的大脑切片解剖,你们就能看到在我回忆那段记忆时,很多脑区正处于活跃状态。02:48Now one brain region that would be robustly active inparticular is called the hippocampus,which for decades hasbeen implicated in processing the kinds of memories that wehold near and dear,which also makes it an ideal target to gointo and to try and find and maybe reactivate a memory.在这其中,海马体是最为持续活跃的脑区域。这一脑区负责处理 对我们来说独具意义的记忆,这一点也使得海马体成为可供深入研究的理想目标,我们可以试着在海马体中找到,并或许激活一段记忆。02:57XL:When you zoom in into the hippocampus,of course youwill see lots of cells,but we are able to find which cells areinvolved in a particular memory,because whenever a cell isactive,like when its forming a memory,刘旭:当你聚焦于海马体,当然你会看到许多脑细胞,但我们也能够找到参与 某一特定记忆的那些细胞,因为每当一个脑细胞在活动时,比如说当它正在形成一段记忆时,03:13it will also leave a footprint that will later allow us to knowthese cells are recently active.它也会同时留下“足迹”,通过这些足迹我们可以得知 这些脑细胞近期有活跃过。03:26recalling:n.回顾;召回;回想/v.召回;回想起;回收;使恢复(recall的ing形式)ethics:n.伦理学;伦理观;道德标准 robustly:adv.要用体力地;粗鲁地;坚定地 in particular:尤其,特别 hippocampus:n.解剖脊椎海马;马头鱼尾怪兽(神话中的一个形象)implicated:adj.有牵连的/v.纠缠(implicate的过去式和过去分词)reactivate:vt.使恢复活动;使恢复现役;使再开工/vi.再度活动;使恢复活力 footprint:n.足迹;脚印SR:So the same way that building lights at night let youknow that somebodys probably working there at any givenmoment,in a very real sense,there are biological sensorswithin a cell that are turned on only when that cell was justworking.史蒂夫:这就好比通过夜晚的大楼灯光,你可以推知有人可能在某一时段在那里工作过。事实上,每一个细胞中都有一些传感器,这些传感器 只有在该细胞工作时开启。03:32Theyre sort of biological windows that light up to let usknow that that cell was just active.它们就像透出亮光的生物窗,告诉我们某一细胞刚刚处于激活状态。03:45XL:So we clipped part of this sensor,and attached that to aswitch to control the cells,and we packed this switch into anengineered virus and injected that into the brain of the mice.刘旭:因此我们获取这种传感器的一小部分,并将这一部分连接到用于控制脑细胞的开关上,然后我们将这一开关植入于人造病毒中,并注射于实验鼠大脑。03:49So whenever a memory is being formed,any active cells forthat memory will also have this switch installed.所以每当一段记忆形成时,人造开关就会被安装到。参与其中的每一个脑细胞04:01SR:So here is what the hippocampus looks like after forminga fear memory,for example.史蒂夫:这就是海马体 形成一段记忆后的形态。04:09The sea of blue that you see here are densely packed braincells,but the green brain cells,the green brain cells are theones that are holding on to a specific fear memory.你们所看到的这一蓝色区域 密集分布着许多脑细胞;但是这些绿色标记的脑细胞,则是与某一特定的恐惧记忆有关。则是与某一特定的恐惧记忆有关。04:13sensors:n.自传感器,感应器;感测器(sensor的复数)light up:照亮;点亮 clipped:adj.省略一部分的;发音清楚的/v.剪除(clip的过去分词)sensor:n.传感器 engineered:adj.设计的,工程/v.设计;指导(engineer的过去分词)injected:充血的/注入的 densely:adv.浓密地;密集地So you are looking at the crystallization of the fleetingformation of fear.所以你们现在看到的就是“恐惧”形成瞬间的结晶所以你们现在看到的就是“恐惧”形成瞬间的结晶04:23Youre actually looking at the cross-section of a memoryright now.你们现在看到的其实是一组记忆横截面04:27XL:Now,for the switch we have been talking about,ideally,the switch has to act really fast.刘旭:现在来看看我们刚刚提到的开关,理论上这个开关的运作速度要非常快。04:31It shouldnt take minutes or hours to work.运作这一开关不能耗上几分钟或几小时。04:36It should act at the speed of the brain,in milliseconds.相反它的工作速度单位 要以大脑的运作速度(毫秒)为单位。04:39SR:So what do you think,Xu?史蒂夫:所以你怎么看,刘旭?04:43Could we use,lets say,pharmacological drugs to activate orinactivate brain cells?你觉得我们能用医学用药 来激活或减退大脑细胞的活动?04:44XL:Nah.Drugs are pretty messy.They spread everywhere.刘旭:行不通吧。药物太难控制了,它们全身乱跑。04:49And also it takes them forever to act on cells.而且等它们作用到脑细胞上就太慢咯。04:53So it will not allow us to control a memory in real time.所以我们不太可能用药物来及时控制记忆。04:56So Steve,how about lets zap the brain with electricity?那史蒂夫,你觉得用电流刺激大脑这个想法如何?05:00crystallization:n.结晶化;具体化 fleeting:adj.飞逝的;转瞬间的/v.迅速移动(fleet的ing形式)cross-section:n.横截面;横断面 ideally:adv.理想地;观念上地 milliseconds:n.计量毫秒(millisecond的复数形式)inactivate:vt.使不活动;使不活泼;阻止活动 messy:adj.凌乱的,散乱的;肮脏的,污秽的;麻烦的 zap:n.活力;意志;杀死;震击/vt.攻击;打败;快速推动/vi.快速移动/int.咝!;糟了!www.XiYuS锡育软件SR:So electricity is pretty fast,but we probably wouldnt beable to target it to just the specific cells that hold onto amemory,and wed probably fry the brain.史蒂夫:嗯,电流的速度确实快,但是我们不太可能将电流精确定位于 参与一段记忆行程的那些特定脑细胞,而且我们很有可能会把大脑烤糊。05:04XL:Oh.Thats true.So it looks like,hmm,indeed we need tofind a better way to impact the brain at the speed of light.刘旭:噢,那倒是真的。嗯,那看来,我们确实得要找到一个更好的方法,能以光速来控制大脑。05:12SR:So it just so happens that light travels at the speed oflight.史蒂夫:对了,光的穿行速度不就是光速嘛。05:21So maybe we could activate or inactive memories by justusing light-XL:Thats pretty fast.所以或许我们就可以 用光来激活或消退记忆.刘旭:那样确实够快05:26SR:-and because normally brain cells dont respond topulses of light,so those that would respond to pulses oflight are those that contain a light-sensitive switch.史蒂夫:而且由于脑细胞通常 对光波没有反应,所以能对光波产生反应的 就是那些挟带光敏开光的细胞。05:33Now to do that,first we need to trick brain cells to respondto laser beams.要做到这点,首先我们必须诱使脑细胞 对镭射光产生反应。05:41XL:Yep.You heard it right.刘旭:对!你们没有听错。05:44hold onto:紧紧抓住,抓住不放;保持住 inactive:adj.不活跃的;不活动的;怠惰的;闲置的 respond to:响应 pulses:n.电子脉冲(pulse的复数);干豆,豆类/v.使跳动;使以脉冲(pulse的三单形式)light-sensitive:adj.光敏的 beams:建梁We are trying to shoot lasers into the brain.我们要试着向大脑发射镭射光。05:45(Laughter)SR:And the technique that lets us do that isoptogenetics.(笑声)史蒂夫:而我们依靠的技术就是光遗传学05:47Optogenetics gave us this light switch that we can use toturn brain cells on or off,and the name of that switch ischannelrhodopsin,seen here as these green dots attached tothis brain cell.通过光遗传学我们得到了这个“光开关”来开启或关闭脑细胞,这个开关就叫做光敏感通道,也就是这里显示的附于这个脑细胞的绿色小点。05:52You can think of channelrhodopsin as a sort of light-sensitiveswitch that can be artificially installed in brain cells so thatnow we can use that switch你们可以将光敏感通道看作一种光敏开关,它可以被人工安置于脑细胞中,因此现在我们就可以使用这一开关06:02to activate or inactivate the brain cell simply by clicking it,and in this case we click it on with pulses of light.只要简单点击一下开关 我们就能激活或减退脑细胞的活动,并且我们用的是光波来点击开关。06:10XL:So we attach this light-sensitive switch ofchannelrhodopsin to the sensor weve been talking aboutand inject this into the brain.刘旭:我们将这一类似光敏开关的紫红质通道蛋白安装于我们刚刚提到的传感器上,并将它注于脑内。06:15So whenever a memory is being formed,any active cell forthat particular memory will also have this light-sensitiveswitch installed in it so that we can control these cells by theflipping of a laser just like this one you see.所以每当一段记忆形成时,光敏开关也会被安装到参与这一特定记忆的每一个细胞上 正如你们所见,我们也就能 通过调控镭射光来控制脑细胞啦。06:24lasers:n.激光激光(laser的复数);激光激光器/v.发射激光(laser的三单形式)artificially:adv.人工地;人为地;不自然地inject:vt.注入;注射 flipping:adj.非常的;糟透的/adv.非常;该死地/v.轻弹;急动;蹦蹦跳跳(flip的ing形式)SR:So lets put all of this to the test now.史蒂夫:那么我们现在就来测试一下吧。06:39What we can do is we can take our mice and then we can putthem in a box that looks exactly like this box here,and thenwe can give them a very mild foot shock so that they form afear memory of this box.我们拿出实验鼠,将它们放到和这个盒子一模一样的盒中,然后施于它们一个轻微的足电击,以使它们对这个盒子形成恐惧记忆。06:42They learn that something bad happened here.它们记得在这个盒子里发生过不好的事。06:52Now with our system,the cells that are active in thehippocampus in the making of this memory,only those cellswill now contain channelrhodopsin.现在在我们的大脑中,海马体内有 参与形成这一恐惧记忆的活跃脑细胞,现在只有这些细胞带有紫红质通道蛋白。06:54XL:When you are as small as a mouse,it feels as if the wholeworld is trying to get you.刘旭:当你像老鼠那么小的时候,会感觉仿佛全世界都要欺压你07:02So your best response of defense is trying to be undetected.而你最好的应对办法 就是尽量把自己藏好。07:08Whenever a mouse is in fear,it will show this very typicalbehavior by staying at one corner of the box,trying to notmove any part of its body,and this posture is called freezing.每当老鼠害怕时,它最典型的表现 就是藏到盒子的一角,一动也不动 我们称这个姿势为“定格”07:13So if a mouse remembers that something bad happened inthis box,and when we put them back into the same box,itwill basically show freezing because it doesnt want to bedetected by any potential threats in this box.因此只要老鼠记得在这个盒子里发生过不愉快的事,当我们将它们放回盒中时,老鼠就会表现出“定格”行为,因为它不想被 盒中任何可能的危险捕获。07:24undetected:adj.未被发现的;未检测到的 posture:n.姿势;态度;情形/vi.摆姿势/vt.作的姿势 detected:adj.检测到的/v.发现(detect的过去分词);检测到;侦测到SR:So you can think of freezing as,youre walking down thestreet minding your own business,and then out of nowhereyou almost run into an ex-girlfriend or ex-boyfriend,andnow those terrifying two seconds where you start thinking,What do I do?Do I say hi?史蒂夫:你们可以将“定格”理解为,你好好地走在路上,想着你自己的事情,突然不经意地你就撞上了你的前女友或前男友,就在那令人恐慌的两秒内,你开始想,“我该怎么做?我要打招呼吗?07:38Do I shake their hand?Do I turn around and run away?我要和他们握手吗?还是转身就跑?07:50Do I sit here and pretend like I dont exist?还是就坐在这里,假装自己不存在?”07:51Those kinds of fleeting thoughts that physically incapacitateyou,that temporarily give you that deer-in-headlights look.这些在你脑中一闪而过的念头令你四肢僵硬、而你脸上的表情就像车头灯照射下的惊恐小鹿。07:53XL:However,if you put the mouse in a completely differentnew box,like the next one,it will not be afraid of this boxbecause theres no reason that it will be afraid of this newenvironment.刘旭:然而当你将实验鼠置于一个截然不同的新盒中,就像这里的第二个盒子,它就不会害怕。因为它没有理由对这个新环境产生恐惧。07:59But what if we put the mouse in this new box but at the sametime,we activate the fear memory using lasers just like wedid before?但是如果我们将实验鼠放于这个新盒中 同时用镭射光 激活之前的那段恐惧记忆08:12Are we going to bring back the fear memory for the first boxinto this completely new environment?我们能否将对于第一个盒子的那段记忆 在这个新环境中重现呢?08:22run into:遭遇,陷入;撞上,撞到;偶然遇见 terrifying:adj.令人恐惧的;骇人的;极大的/v.使害怕,使恐怖(terrify的现在分词)turnaround:转向反方向;(生意或经济)好转;船只留港 incapacitate:vt.使无能力;使不能;使不适于SR:All right,and heres the million-dollar experiment.史蒂夫:不错,这就是那个耗价百万的实验。08:29Now to bring back to life the memory of that day,Iremember that the Red Sox had just won,it was a greenspring day,perfect for going up and down the river andthen maybe going to the North End to get some cannolis,#justsaying.现在就让我们把那一天的记忆重现,我记得那一天波士顿红袜队正巧打赢一场比赛,那是一个绿意盎然的春日,最适宜在小河中划船,然后也许去波士顿北区 买几个奶油甜馅煎饼卷 啊,只是说说而已。08:31Now Xu and I,on the other hand,were in a completelywindowless black room not making any ocular movementthat even remotely resembles an eye blink because our eyeswere fixed onto a computer screen.事实上刘旭和我,当时正在一间没有窗户的小黑屋里,双眼一眨不眨 因为我们的目光正牢牢盯住电脑屏幕08:45We were looking at this mouse here trying to activate amemory for the first time using our technique.我们当时正看着这只老鼠 第一次尝试用我们的技术 来激活一段记忆。08:57XL:And this is what we saw.刘旭:而这就是我们看到的:09:01When we first put the mouse into this box,its exploring,sniffing around,walking around,minding its own business,because actually by nature,mice are pretty curious animals.当我们第一次将老鼠放进这只盒子时,它在探索,这边嗅嗅,那边转转,完全沉浸在自己的世界里,事实上,老鼠天性就是好奇心旺盛的动物。事实上,老鼠天性就是好奇心旺盛的动物。09:04Sox:n.(美)短袜;鞋垫;喜剧(sock的复数)up and down:上上下下;到处;前前后后;来来往往 cannolis:n.奶油甜馅煎饼卷 onthe other hand:另一方面 windowless:adj.没有窗的 ocular:adj.眼睛的;视觉的;目击的/n.光目镜 remotely:adv.遥远地;偏僻地;(程度)极微地,极轻地 resembles:似 blink:vt.眨眼;使闪烁/vi.眨眼;闪烁/n.眨眼;瞬间;闪光 sniffing:n.嗅探/v.嗅闻;用鼻吸气;发觉;嗤之以鼻地说(sniff的ing形式)They want to know,whats go