Ed Boyden: A light switch for neurons

翻译人员: Bear Jin 校对人员: Xu Jiang

花点时间回想你的一天

Think about your day for a second.

You woke up, felt fresh air on your face as you walked out the door,

你清晨醒来，走出房门的时候感受到清风拂过你的脸颊

encountered new colleagues and had great discussions

巧遇新的同事，与其谈天说地

当你发现新事物时则心怀敬畏

and felt in awe when you found something new.

但我确定今天会有些你没有想到的事情--

But I bet there's something you didn't think about today,

一些如此贴近生活的

something so close to home,

但你可能完全忽略的事情。

you probably don't think about it very often at all.

其中包含的所有的感知能力，感情

And that's that all those sensations, feelings, decisions and actions

决策和行动

都直接受控于在你头部的电脑

are mediated by the computer in your head

叫做大脑的部分。

called your brain.

Now, the brain may not look like much from the outside --

大脑看可不像外表看起来那样--

只是几磅桃灰色的肉块，

a couple pounds of pinkish-gray flesh,

非结晶的固体--

amorphous.

But the last 100 years of neuroscience have allowed us to zoom in on the brain

但是经过上百年积淀的神经学

让我们能进一步的研究大脑，

and to see the intricacy of what lies within.

并了解大脑的错综复杂。

And they've told us that this brain is an incredibly complicated circuit

研究告诉我们大脑

是由上千亿个神经元细胞

made out of hundreds of billions of cells called neurons.

组成的难以想象的复杂电路

Now, unlike a human-designed computer,

不同于人类设计的电脑

where there's a fairly small number of different parts,

那种由较少的不同元件组成的--

我们了解它们如何工作，因为是我们人类设计出了它们--

and we know how they work because we humans designed them,

the brain is made out of thousands of different kinds of cells,

大脑由上千种不同的细胞组成

也许是上万种

maybe tens of thousands.

They come in different shapes; they're made out of different molecules;

它们分化成不同的形状；它们分泌出不同分子；

它们延伸并连接大脑的不同地区。

they project and connect to different brain regions.

它们对于不同的疾病也表现出不同的方式。

They also change in different ways in different disease states.

说的具体一点

Let's make it concrete.

There's a class of cells,

有一种细胞，

a fairly small cell, an inhibitory cell, that quiets its neighbors.

一种较小的，抑制性细胞，能够抑制周围细胞。

这是一种其萎缩能导致类似神经分裂症状的细胞

It's one of the cells that seems to be atrophied

in disorders like schizophrenia.

It's called the basket cell.

这叫做篮细胞

And this cell is one of the thousands of kinds of cell

它是我们正在研究的成千上万种细胞

中的一种

that we're learning about.

New ones are being discovered every day.

每天都会有发现新型的细胞。

第二个例子：

As just a second example:

these pyramidal cells, large cells, can span a significant fraction

这些锥体细胞，大型的细胞

他们分布在大脑的很多部位

of the brain.

它们易受刺激。

They're excitatory.

其中的一部分细胞

And these are some of the cells that might be overactive

可能会因过度的活动而导致疾病类似癫症。

in disorders such as epilepsy.

这些细胞中每一个

Every one of these cells is an incredible electrical device.

都是一个神奇的电子元件

They receive inputs from thousands of upstream partners

它们从上游细胞接收信息

然后编辑出它们自己的输出信息，

and compute their own electrical outputs,

which then, if they pass a certain threshold,

然后，如果这些信息通过了特定的界限，

就会传递到下游上千个细胞那里。

will go to thousands of downstream partners.

这个仅仅会花费一毫秒左右的时间的过程

And this process, which takes just a millisecond or so,

happens thousands of times a minute in every one of your 100 billion cells,

在你身上的每个1万亿个细胞中

每分钟发生上千次，

as long as you live and think and feel.

只要你活着

思考着感受着。

So how are we going to figure out what this circuit does?

我们将如何解释这些回路的运作呢？

主观上，我们能刺激这些回路

Ideally, we could go through this circuit

把不同种细胞反复刺激

and turn these different kinds of cell on and off

and see whether we could figure out

看我们是否能了解

which ones contribute to certain functions

哪种细胞作用于特定的功用

and which ones go wrong in certain pathologies.

哪种细胞出错会引起特定的病理

如果我们能激活细胞，我们就能了解它们能释放哪种能量

If we could activate cells, we could see what powers they can unleash,

他们是如何启动和维持的.

what they can initiate and sustain.

如果我们能把它们全部切断

If we could turn them off,

then we could try and figure out what they're necessary for.

我们就可能弄清楚它们的必要性。

这就是今天我要告诉大家的故事。

And that's the story I'm going to tell you about today.

老实说，

And honestly, where we've gone through over the last 11 years,

我们试图寻找方法

through an attempt to find ways

of turning circuits and cells and parts and pathways of the brain

来控制大脑中的回路，细胞，部分的组织还有

它的传输途径

on and off,

这不仅是对科学的探索，

both to understand the science

and also to confront some of the issues that face us all as humans.

也是直面人类所面临的

一些问题。

Now, before I tell you about the technology,

在我告诉大家这项技术之前

the bad news is that a significant fraction of us in this room,

坏消息是我们之间的绝大数人

如果你们活的够久远的话

if we live long enough,

will encounter, perhaps, a brain disorder.

将会面临，也许，脑部疾病

如今，10亿人

Already, a billion people have had some kind of brain disorder

已经患有某些脑部疾病

阻碍它们生活

that incapacitates them.

The numbers don't do it justice, though.

虽然这数字无法准确的表现出其严重性

These disorders -- schizophrenia, Alzheimer's,

这些疾病--精神分裂症，老年痴呆症

抑郁症，成瘾症--

depression, addiction --

they not only steal away our time to live,

它们不仅榨取我们的生命，而且篡改我们生存的意义

they change who we are.

They take our identity and change our emotions

它剥夺了我们的性格也改变了我们的情感--

and change who we are as people.

更改变了我们做人的本质

Now, in the 20th century,

如今在20世纪，

通过治疗脑部疾病的

there was some hope that was generated

through the development of pharmaceuticals for treating brain disorders.

制药业的发展浮现出的一些希望

同时很多药物被研发出

And while many drugs have been developed

that can alleviate symptoms of brain disorders,

能减缓脑部疾病的症状

实际上没有那种病被认为是能被治愈的

practically none of them can be considered to be cured.

In part, that's because, if you think about it,

其中一部分是因为，我们大脑浸泡在化学物质当中

we're bathing the brain in a chemical --

这复杂的回路

this elaborate circuit, made of thousands of different kinds of cell --

由上千种不同类型的细胞组成

正浸泡在液体当中

is being bathed in a substance.

That's also why most of the drugs, not all, on the market

这也是为什么，市面上大部分的药物，不全都

会引起某些严重的副作用。

can present some kind of serious side effect too.

如今有些人通过在大脑植入电击器

Now some people have gotten some solace from electrical stimulators

来改善某些疾病。

that are implanted in the brain,

for Parkinson's disease or cochlear implants.

对于帕金森症

耳蜗移植电击器

These have indeed been able to bring some kind of remedy

的确能够

带给患有一些特殊疾病的患者

to people with certain kinds of disorders.

一些治疗效果

But electricity also will go in all directions --

但是电流还是会往四散开去--

the path of least resistance --

找软柿子捏（从阻碍最小的地方通过）

which is where that phrase, in part, comes from,

这也是这句谚语的，部分的，出处

and will also affect normal circuits,

电流不仅作用在我们需要修复的细胞还会影响到那些正常的回路

as well as the abnormal ones you want to fix.

再一次，我们绕回到了

So again, we're sent back to the idea of ultraprecise control:

超精确控制的问题上

Could we dial in information precisely where we want it to go?

我们是否能把信息精确的传输到我们想要地方？

当11年前我开始研究神经科学

So, when I started in neuroscience 11 years ago --

I had trained as an electrical engineer and a physicist --

我受训成为一个电学工程师和物理学家

the first thing I thought about was,

而且第一件我想到的事

if these neurons are electrical devices,

如果这些神经元是电子元件

all we need to do is to find some way of driving those electrical changes

所有我们要做的是找到某些方法

在一定距离控制电流的变化

at a distance.

如果我们能刺激单独一个细胞

If we could turn on the electricity in one cell but not its neighbors,

而不牵涉它周边

that'd give us the tool to activate and shut down these different cells

那就我们就有了能激活和关闭各种不同细胞的工具

了解它们的作用和他们如何作用

to figure out what they do

and how they contribute to the networks in which they're embedded.

在它们位于的脑部网络

同样这给了我们需要的超精确控制

It would also allow us to have the ultraprecise control we need

来修复出错

to fix the circuit computations that have gone awry.

的回路

Now, how are we going to do that?

如今我们将怎么做呢？

Well, there are many molecules that exist in nature

自然中有很多分子

能够把光转化为电流

which are able to convert light into electricity.

你可以把它们看做小蛋白质

You can think of them as little proteins that are like solar cells.

像太阳能细胞

If we install these molecules in neurons somehow,

如果我们能用某种方法把这些分子注入到神经元中

then these neurons would become electrically drivable with light,

这些神经元就能转型成光控的电子元件

and their neighbors, which don't have this molecule, would not.

那些周边的细胞，那些没有接受分子的，就不会转型

There's one other magic trick you need to make this happen:

另外还有一个你需要知道的小窍门，

就是把光注入脑中。

the ability to get light into the brain.

The brain doesn't feel pain.

这么做--大脑不会感知到痛苦--你能--

Taking advantage of all the effort

充分利用脑中

that's gone into the internet, telecommunications, etc.,

类似互联网和沟通的功能--

you can put optical fibers connected to lasers

把光纤连接到激光束中

to activate -- in animal models, for example, in preclinical studies --

以此来激活，比如说动物的细胞

在潜伏期的研究中

these neurons and see what they do.

要了解这些神经元的功用

那我们应该怎么做呢？

So how do we do this?

Around 2004, in collaboration with Georg Nagel and Karl Deisseroth,

大概在2004年

在与格哈德·内格尔和卡尔·戴斯洛合作的时候

this vision came to fruition.

假想得到了最终的成功

There's a certain alga that swims in the wild,

自然界中有一种特定的海藻

and it needs to navigate towards light in order to photosynthesize optimally.

它就有趋光性

来达到最理想的光合效果

And it senses light with a little eyespot,

它用一个小眼点来感知光线

which works not unlike how our eye works.

但其工作原理和人眼大相径庭

In its membrane, or its boundary,

在它的细胞膜，或者它的边界

it contains little proteins

含有少量的蛋白质

能把光转化为电流

that indeed can convert light into electricity.

这些分子被叫做槽型视紫质（TRB）

These molecules are called channelrhodopsins.

And each of these proteins acts just like that solar cell

这种蛋白质就像我告诉过你们的太阳能细胞那样运作

that I told you about.

当蓝光照射时，它会打开一个小口

When blue light hits it,

it opens a little hole and allows charged particles to enter the eyespot;

允许带点的微粒进入眼点中

这样眼点就有了电信号

that allows this eyespot to have an electrical signal,

就像是用太阳能细胞给电池充电一般

just like a solar cell charging a battery.

So what we need to do is take these molecules

我们需要做的就是提取这些分子

然后用某种方法注入到神经元中

and somehow install them in neurons.

And because it's a protein,

同时因为这是蛋白质

it's encoded for in the DNA of this organism.

由生物的DNA编码而成

So all we've got to do is take that DNA,

所以我们所要做的就是提取DNA

put it into a gene therapy vector, like a virus,

注入到基因载体上，比如病毒

and put it into neurons.

然后把病毒注入到神经元中

And this was a very productive time in gene therapy,

结果证明基因载体是一个很直接的方法

and lots of viruses were coming along,

病毒长驱直入

so this turned out to be fairly simple.

证实了操作的简易性

Early in the morning one day in the summer of 2004,

在2004年夏天的一个早晨

we gave it a try, and it worked on the first try.

我们实物操作了一番，第一次尝试有了起效

你提取出DNA并注入到神经元中

You take this DNA and put it into the neuron.

The neuron uses its natural protein-making machinery

神经元用它自身的蛋白质合成器

to fabricate these little light-sensitive proteins

来组装出这些小型的光敏蛋白质

并使其分不到细胞各处

and install them all over the cell, like putting solar panels on a roof.

就像在顶层架设太阳能板

And the next thing you know,

接下去

you have a neuron which can be activated with light.

你就有了个光敏的神经元

这是个很有效的工具

So this is very powerful.

One of the tricks you have to do is figure out how to deliver these genes

你要做的步骤

就是设法把这些基因注入到你需要的细胞内

to the cells you want and not all the other neighbors.

而不是其他周边的细胞

你可以完成；你能转变这些病毒

And you can do that;

you can tweak the viruses so they hit some cells and not others.

让它们只针对一些细胞而涉及到其他细胞

还有其他基因方式能

And there's other genetic tricks you can play

得到这种光敏细胞

in order to get light-activated cells.

如今这领域叫做光遗传学

This field has now come to be known as "optogenetics."

And just as one example of the kind of thing you can do,

举个例子来说明你要做的，

你可以在一个复杂的网络系统

you can take a complex network,

use one of these viruses to deliver the gene

利用一种病毒来传递这种基因

在密集的细胞区域只针对一种细胞

just to one kind of cell in this dense network.

And then when you shine light on the entire network,

接着当你照射整个区域的时候

just that cell type will be activated.

只有那些特定的细胞被激活

For example, let's consider that basket cell I told you about earlier,

比如说，用篮细胞来做例子会更简单一点

就是那种萎缩导致精神分裂

the one that's atrophied in schizophrenia

有抑制作用的细胞

and the one that is inhibitory.

如果我们能把基因注入到这些细胞中--

If we can deliver that gene to these cells --

而且他们不会引起基因的表现型有所改变--

they won't be altered by the expression of the gene, of course --

接着用蓝光照射整个脑组织

then flash blue light over the entire brain network,

just these cells are going to be driven.

只有蓝细胞会被激活

而当无光线的时候，这些细胞就变回普通的细胞

And when the light turns off, these cells go back to normal;

没有产生不良的后果

there don't seem to be adverse events.

Not only can you study what these cells do,

不仅你能了解到这些细胞的功用

what their power is in computing in the brain,

在大脑运作中它们的能效

而且你也能尝试解决--

you can also use this to try to figure out

也许我们可以激活这些细胞的活性，

if we could jazz up the activity of these cells

如果它们真的萎缩的话。

if indeed, they're atrophied.

I want to tell you some short stories about how we're using this

现在我想告诉你一些小故事

关于我们怎么利用这技术的,

both at the scientific clinical and preclinical levels.

在科学，临床阶段和临床前阶段的研究。

One of the questions that we've confronted is:

在我们遭遇到的问题中有一个

What signals in the brain mediate the sensation of reward?

是，大脑用什么样的信号来代表奖励的感觉呢？

Because if you could find those,

因为如果我们找到的话

those would be some of the signals that could drive learning;

那能够驱使细胞学习的信号

大脑就会为了奖励竭尽全力

the brain will do more of what got that reward.

同时也是这些出错的信号引起疾病类似成瘾症

These are also signals that go awry in disorders such as addiction.

如果我们能够知道是哪些细胞的话

So if we could figure out what cells they are, we could maybe find new targets

我们可能就有新的靶细胞

来专门设计或者挑选药物来对抗疾病

for which drugs can be designed or screened against

或者找到植入电击器的位置

or maybe places where electrodes could be put in

来帮助那些有着严重残疾的病人

for people who have severe disability.

To do that, we came up with a very simple paradigm

为了做到这些，我们想出了一个简单的例子

在菲奥雷拉集团的协助下

in collaboration with the Fiorillo group,

在盒子的一边

where, if the animal goes to one side of this little box,

如果动物经过这里，就会被光波照射到

it gets a pulse of light.

来区别不同细胞对光的感应能力.

And we'll make different cells in the brain sensitive to light.

那如果这些细胞是识别为被奖励的

If these cells can mediate reward, the animal should go there more and more.

那动物就会多次的经过那里

这就是大致的经过

And that's what happens.

The animal goes to the right-hand side and pokes his nose there

动物会向右转并用鼻子顶那块地方

每次它做这个动作就会有一道蓝光照射

and gets a flash of blue light every time he does it.

那它就会为此重复千上百次

He'll do that hundreds of times.

这些是多巴胺神经元

These are the dopamine neurons,

你们中的一些可能可能听说过它在大脑的快感中枢某处

in some of the pleasure centers in the brain.

现在我们所展示的简短的步骤

We've shown that a brief activation of these is enough to drive learning.

就足够，确定的，来诱导学习行为

如今我们概括出大致的观点

Now we can generalize the idea.

不是大脑中的某一点

Instead of one point in the brain, we can devise devices that span the brain,

我们可以发明一些能够桥接大脑的设备

来把光照射成三维的模式--

that can deliver light into three-dimensional patterns --

利用光纤的巧妙排列

arrays of optical fibers,

每个光纤都有自身独立的微型光源.

each coupled to its own independent miniature light source.

接着我们在生物体上试验

Then we can try to do things in vivo

测试那些已经在培养皿中完成的实验--

that have only been done to date in a dish,

like high-throughput screening throughout the entire brain

就像是给整个大脑做了高速的扫描一般

来确定特定的信号会触发哪些特定的事情

for the signals that can cause certain things to happen

或者它们会成为临床上很好的

or that could be good clinical targets for treating brain disorders.

治疗脑部疾病的新目标

另外一件我想说的事是

One story I want to tell you about is:

我们如何寻找靶细胞来治疗创伤后应激障碍--

How can we find targets for treating post-traumatic stress disorder,

这是一种不受控制的焦虑恐慌的症候群

a form of uncontrolled anxiety and fear?

我们要做的一件事

One of the things that we did was to adopt a very classical model of fear.

接受一个经典的恐怖模式

This goes back to the Pavlovian days.

那就回到了巴甫洛夫的时代

It's called Pavlovian fear conditioning, where a tone ends with a brief shock.

也被称作巴甫洛夫恐惧条件反射

在响声后的短暂电击

The shock isn't painful, but it's a little annoying.

电极并不疼痛，但是有点烦人

久而久之--这里的例子，老鼠

And over time -- in this case, a mouse,

是一个很好的动物典型，在试验中广泛使用--

which is a good animal model, commonly used in such experiments --

动物学会去害怕响声

the animal learns to fear the tone.

会表现出呆滞的反应

It will react by freezing, sort of like a deer in the headlights.

有点像鹿被车灯照射后的反应一样

Now the question is: What targets in the brain can we find

如今的问题是，大脑中哪些目标位置

that allow us to overcome this fear?

能让我们克服这种恐惧？

我们所做的就是再一次播放那

So we play that tone again, after it's been associated with fear.

当已经和恐惧联系起来的响声

但是我们激活大脑中的靶细胞，每次不同的位置

But we activate different targets in the brain,

利用光纤阵列来演示出之前那样的图片

using that optical fiber array I showed on the previous slide,

来尝试找出能让大脑克服

in order to try and figure out

which targets can cause the brain to overcome that memory of fear.

恐惧记忆的靶细胞

这简短的录像

This brief video shows you one of these targets

展示给大家一些我们正在研究的几个靶细胞

that we're working on now.

This is an area in the prefrontal cortex, a region where we can use cognition

这是前额皮层的一部分

一块能让我们用感知来尝试克服厌恶情绪的区域

to try to overcome aversive emotional states.

动物将听到同样的响声--以及一束光线

The animal hears a tone. A flash of light occurs.

光线不伴随声音，但是你也能看到动物呆滞的反应

There's no audio, but you see that the animal freezes --

这声响意味着坏的消息

the tone used to mean bad news.

在左下角有个小型的闹钟

There's a little clock in the lower left-hand corner.

你能看到老鼠用了大约两分钟僵立在那里

You can see the animal is about two minutes into this.

下一个片段

This next clip is just eight minutes later.

是八分钟之后

And the same tone is going to play, and the light is going to flash again.

同样的响声，和相同的光线再一次的出现

好，开始了，就现在

OK, there it goes. Right ... now.

正如你所见，只用了10分钟的实验

And now you can see, just 10 minutes into the experiment,

我们就用光激活了大脑的这部分区域

that we've equipped the brain, by photoactivating this area,

来克服恐惧记忆

to overcome the expression of this fear memory.

的表现行为

近几年里，我们正回溯本源

Over the last couple years, we've gone back to the tree of life,

因为我们想找到控制大脑的方法

because we wanted to find ways to turn circuits in the brain off.

如果我们能够控制的话，那就可能是极具影响的

If we could do that, this could be extremely powerful.

If you can delete cells for a few milliseconds or seconds,

如果让细胞失效就算几毫秒或者几秒的话

you can figure out what role they play in the circuits in which they're embedded.

就能了解到它们所在位置的脑电路

所扮演的本质的角色

We surveyed organisms from all over the tree of life --

如今我们已经调查了生物界所有的生物--

所有生物除了动物，我们并没有发现太大的差异。

every kingdom of life but animals; we see slightly differently.

我们发现了各种各样的分子，被命名为感光紫红蛋白或者远古感光蛋白

We found molecules called halorhodopsins or archaerhodopsins,

会对绿色和黄色光线作出反应

that respond to green and yellow light.

And they do the opposite of the molecule I told you about before,

它们的反应是与之前我所提到的蓝光

活性槽型视紫质的反应恰恰相反

with the blue light activator, channelrhodopsin.

Let's give an example of where we think this is going to go.

举个例子来说明具体的情况

Consider, for example, a condition like epilepsy,

比如说癫痫这个症状

where the brain is overactive.

起因是大脑过度活跃

Now, if drugs fail in epileptic treatment,

如果癫痫药物治疗失败

one of the strategies is to remove part of the brain,

其他一种方法就是移除那部分大脑

但是这显然是不可逆的过程，而且会引起副作用

but that's irreversible, and there could be side effects.

那如果我们让那部分大脑休眠一会儿

What if we could just turn off that brain for the brief amount of time

知道症状全部消失

until the seizure dies away,

and cause the brain to be restored to its initial state,

再让大脑恢复到原来的阶段--

like a dynamical system that's being coaxed down into a stable state?

就好像把一个活跃的系统诱骗到一个稳定的系统一样

这动画只是为了解释

This animation tries to explain this concept

where we made these cells sensitive to being turned off with light,

我们能利用光源来控制脑细胞这个概念

当我们用光照射时

and we beam light in,

and just for the time it takes to shut down a seizure,

照射的时间也仅仅是能够刚好让症状消除

我们希望实验能够成功

we're hoping to be able to turn it off.

暂时我们还没有这方面的实验数据展示给大家

We don't have data to show you on this front,

但是我们对此充满期待

but we're very excited about this.

I want to close on one story, which we think is another possibility,

现在我想用一个故事来结束我的演讲

我们认为此技术能有其他用途---

which is that maybe these molecules, if you can do ultraprecise control,

如果能超精确控制这些感光蛋白

能够在脑中

can be used in the brain itself to make a new kind of prosthetic,

形成一个新型的假肢，光学的价值

an optical prosthetic.

我曾说过，电击器并不普遍

I already told you that electrical stimulators are not uncommon.

如今只有75000位帕金森病人植入了脑部电击器

Seventy-five thousand people

have Parkinson's deep-brain stimulators implanted,

大约10万人在耳蜗中植入电击器

maybe 100,000 people have cochlear implants, which allow them to hear.

通过这样来恢复他们的听觉

另一件事，就是你要让这些基因细胞移植入细胞中

Another thing -- you've got to get these genes into cells.

基因治疗的新希望也就此诞生了

A new hope in gene therapy has been developed,

because viruses like the adeno-associated virus --

因为像腺类病毒这类病毒

可能我们大多数都有携带

which probably most of us around this room have;

但它不会引发任何症状

it doesn't have any symptoms --

它已经在上百名病人体内应用治疗

have been used in hundreds of patients

to deliver genes into the brain or the body.

来转送基因进入大脑或者身体内

And so far, there have not been serious adverse events

目前为止，还有没有因为此病毒

而引起任何严重不良反应的报告

associated with the virus.

There's one last elephant in the room: the proteins themselves,

还有最后一点要重视的大隐患，就是蛋白质其本身

which come from algae, bacteria and funguses

那些来自于藻类，细菌以及真菌

and all over the tree of life.

以及来自生物界的各种蛋白质

Most of us don't have funguses or algae in our brains,

我们大多数脑子没有真菌或者藻类的存在

那如果我们把它们放入脑中会怎么样呢？

so what will our brain do if we put that in?

我们大脑是否会排斥它？免疫系统是否会反应？

Will the cells tolerate it? Will the immune system react?

早期的时候--我们并没有在人体里做实验--

It's early -- these haven't been done in humans yet --

但是我们做了其他各种研究

but we're working on a variety of studies to examine this.

来评估这方法

目前为止，我们还没有因这些分子或者

So far, we haven't seen overt reactions of any severity

因光照大脑

to these molecules

or to the illumination of the brain with light.

而产生的严重不良反应

这还是初步的研究，就算如此，我们很激动

So it's early days, to be upfront, but we're excited about it.

我想用一个故事来结束我的演讲

I wanted to close with one story,

which we think could potentially be a clinical application.

我们认为这有可能

成为一种临床的疗法

Now, there are many forms of blindness

失明有很多种类

大多关于

where the photoreceptors -- light sensors in the back of our eye --

我们的眼球内部的光受体的损害。

are gone.

And the retina is a complex structure.

我们的视网膜是个很复杂的结构

Let's zoom in on it so we can see it in more detail.

我们来放大，仔细研究一下

照片中的感光受体在顶部

The photoreceptor cells are shown here at the top.

The signals that are detected by the photoreceptors are transformed

被感光受体接收到的光信号

经过各种转化

via various computations

最终从上而下，从神经节细胞

until finally, the layer of cells at the bottom, the ganglion cells,

传输信息到大脑出

relay the information to the brain,

以此来获得视觉

where we see that as perception.

很多种类的失明，比如色素性视网膜炎

In many forms of blindness, like retinitis pigmentosa

or macular degeneration,

或者黄斑部变性

the photoreceptor cells have atrophied or been destroyed.

感光细胞是萎缩或者有损伤的

Now, how could you repair this?

那我们如何才能修复呢？

It's not even clear that a drug could cause this to be restored,

还没有证据证明药物可以对治疗这些疾病

since there's nothing for the drug to bind to.

因为还没有针对的特效药

On the other hand, light can still get into the eye.

但是，光还是能进入眼球的

眼球还是通透的，你也能看到光线能够进入

The eye is still transparent and you can get light in.

所以，如果我们能把这些单细胞感光紫红质蛋白和其他分子

So what if we could take these channelrhodopsins and other molecules

注入到那些正常的细胞中

and install them on some of these other spared cells

把它们转化为一台台小的摄像机

and convert them into little cameras?

因为眼球内部有很多细胞

And because there are so many of these cells in the eye,

有可能，他们会成为高清的相机

potentially, they could be very high-resolution cameras.

这就是我们所在做的

This is some work that we're doing,

我们合作人之一

led by one of our collaborators, Alan Horsager at USC,

艾伦·霍斯葛

and being sought to be commercialized by a start-up company, Eos Neuroscience,

也正在美国卫生研究所的资助下将其技术

商业化运作

which is funded by the NIH.

What you see here is a mouse trying to solve a six-arm maze.

现在你所看到的是一个走迷宫的老鼠

这是六臂的迷宫，迷宫中有些许水

There's a bit of water to motivate the mouse to move or he'll just sit there.

来刺激老鼠移动，否则它只会呆在某处

当然，这迷宫的目的

The goal of this maze is to get out of the water

是为了让水流入一个

and go to a little platform that's under the lit top port.

顶光源的平台

老鼠很聪明，最终走出了这迷宫

Mice are smart, so this one solves the maze eventually,

but he does a brute-force search.

但是这是靠蛮力解决的

He's swimming down every avenue until he finally gets to the platform.

它游过了每条分支最终才找到了平台

He's not using vision to do it.

所以它没有利用视觉来解决这问题

These different mice are different mutations

这些老鼠有着不一样的突变基因

各自代表着人类不用种类的失明症状

that recapitulate different kinds of blindness that affect humans.

所以我们有很小心的探索不同种类的失明情况下

So we're being careful in trying to look at these different models

找出一个普遍的解决方法

so we come up with a generalized approach.

那我们如何解决呢？

So how can we solve this?

我们就完全按照之前片子里讲的那样

We'll do exactly what we outlined in the previous slide.

把蓝光感光蛋白

We'll take these blue light photo sensors

注入到眼球最后方的视网膜的

and install them onto a layer of cells

一层细胞上

in the middle of the retina in the back of the eye

and convert them into a camera --

把它们转化为一台台相机

just like installing solar cells all over those neurons

就好像这些神经元上布满了太阳能细胞一样

让它们接受光信号

to make them light-sensitive.

Light is converted to electricity on them.

并把光信号转化为电信号

So this mouse was blind a couple weeks before this experiment

这老鼠实验前几周就瞎了

and received one dose of this photosensitive molecule on a virus.

只接受过一次携带有感光受体分子的病毒注射

你现在可以看到，老鼠能够避开墙壁

And now you can see, the animal can indeed avoid walls

找到有亮光的平台

and go to this little platform

视觉得到了恢复

and make cognitive use of its eyes again.

为了指出其中的意义：

And to point out the power of this:

这些动物走到平台的时间

these animals can get to that platform

just as fast as animals that have seen their entire lives.

和那些没有瞎的东西用时是一样的

虽然还处于临床前阶段

So this preclinical study, I think, bodes hope

但是我认为这是个好兆头

for the kinds of things we're hoping to do in the future.

未来我们希望我们能够成功

最后，我想指出我们正研究的一种

We're also exploring new business models for this new field of neurotechnology.

针对神经科学这新领域的商业模式

我们发明了这些工具

We're developing tools and sharing them freely

但是我们愿意和全世界的人共同分享

with hundreds of groups all over the world

这样人们才能进一步研究并尝试治疗其他各种疾病

for them to study and try to treat different disorders.

我们希望，通过了解大脑的神经网络

Our hope is that by figuring out brain circuits

通过某种程度的手术，能让我们修复并设计神经网络

at a level of abstraction that lets us repair them and engineer them,

我们会继续研究我之前讲过的几种疾病

we can take some of these intractable disorders I mentioned earlier,

特别是那几种从未被治愈过的

practically none of which are cured,

他们在21世纪将会成为历史

and in the 21st century, make them history.

谢谢

Thank you.

(Applause)

（掌声）

Juan Enriquez: So some of this stuff is a little dense.

Juan Enriquez(JE)：您的演讲有些深奥啊。

(Laughter)

（笑声）

但是利用光

But the implications of being able to control seizures or epilepsy

来控制癫痫或者抽搐

with light instead of drugs

而不是用药物

and being able to target those specifically

还要能够精确地控制靶细胞

is a first step.

是第一步。

The second thing that I think I heard you say

据我所听到的，第二步

is you can now control the brain in two colors,

是用两种色彩的光来控制大脑

就好像开关一样

like an on-off switch.

艾德·博伊登(EB):没错.

Ed Boyden: That's right.

JE：这让每个大脑中的神经冲动变成二进制的代码

JE: Which makes every impulse going through the brain a binary code.

EB：是的

EB: Right.

With blue light, we can drive information, and it's in the form of a one.

当蓝灯亮起时，我们能传输信息。就类似于代码1

等光关闭了，就类似代码0

And by turning things off, it's more or less a zero.

我们的希望是最终建造一个大脑协同处理器

Our hope is to eventually build brain coprocessors that work with the brain

来和大脑一起运作

以此来帮助那些有残疾的人

so we can augment functions in people with disabilities.

JE: And in theory, that means that, as a mouse feels, smells, hears, touches,

那就是理论上，这代表着

老鼠的感觉，嗅觉

听觉和触觉

you can model it out as a string of ones and zeros.

你都能把它整合到一串0和1

EB: Yeah. We're hoping to use this as a way of testing

EB：的确是这样的。我们希望通过这种测试

来确定哪种神经代码代表着哪种行为举止

what neural codes can drive certain behaviors

或者是想法或者感受

and certain thoughts and certain feelings

通过这样来更多的了解大脑

and use that to understand more about the brain.

JE: Does that mean that someday you could download memories

JE：这是不是意味着某天你能下载记忆

and maybe upload them?

或者上传记忆呢？

EB: That's something we're starting to work on very hard.

EB：我们着手的某些工作是很复杂的

我们还在继续的研究

We're now working on trying to tile the brain with recording elements, too,

我们也在尝试去标记下这个大脑记录数据

so we can record information and then drive information back in --

我们就能记录信息，并把信息传输回大脑--

sort of computing what the brain needs

类似于了解什么是大脑所需的

in order to augment its information processing.

来增强它的信息处理效率.

JE: Well, that might change a couple things. Thank you.

JE: 嗯，这会改变我的世界的。谢谢! (EB: 谢谢.)

EB: Thank you.

（掌声）

(Applause)