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如何观察大脑内部 – 译学馆
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如何观察大脑内部

Carl Schoonover: How to look inside the brain

这是一张一千年前关于大脑的绘画
This is a thousand-year-old drawing of the brain.
一个关于视觉系统的图像
It’s a diagram of the visual system.
有些东西在今天看来也很熟悉
And some things look very familiar today.
底下是两只眼睛,视觉神经从它们后面伸出来
Two eyes at the bottom, optic nerve flowing out from the back.
这是个很大的鼻子
There’s a very large nose
看起来它并没有连接到特殊的部位
that doesn’t seem to be connected to anything in particular.
如果我们把这个
And if we compare this
跟最近的视觉系统的表现形式进行对比
to more recent representations of the visual system,
你会发现情况变得异常复杂
you’ll see that things have gotten substantially more complicated
在经历了几千年之后
over the intervening thousand years.
这是因为今天我们可以看见大脑里面的东西
And that’s because today we can see what’s inside of the brain,
而不只是它大致的形状
rather than just looking at its overall shape.
想象下如果你想知道电脑是如何工作的
Imagine you wanted to understand how a computer works
你能看到的只是键盘,鼠标和屏幕
and all you could see was a keyboard, a mouse, a screen.
你真的不会那么走运(明白它是怎么工作的)
You really would be kind of out of luck.
你会想要打开它,拆开它
You want to be able to open it up, crack it open,
看看里面电线的连接
look at the wiring inside.
直到一百多年以前
And up until a little more than a century ago,
没有人能够这样对待大脑
nobody was able to do that with the brain.
没人看到过大脑的回路
Nobody had had a glimpse of the brain’s wiring.
那是因为如果你把大脑从头盖骨里拿出来
And that’s because if you take a brain out of the skull
从中切出一个薄片
and you cut a thin slice of it,
把它放在即便很强大的显微镜下面
put it under even a very powerful microscope,
那里什么都没有
there’s nothing there.
它是灰色的,没有固定形状
It’s gray, formless.
没有结构。它不会告诉你任何东西
There’s no structure. It won’t tell you anything.
这些都在19世纪末发生了改变
And this all changed in the late 19th century.
忽然间,人们发明了新的大脑组织的化学染料
Suddenly, new chemical stains for brain tissue were developed
这些染料让我们第一次看到大脑的回路
and they gave us our first glimpses at brain wiring.
这个电脑被打开了
The computer was cracked open.
真正开启现代神经科学的是
So what really launched modern neuroscience
一种叫高尔基染色法的染料
was a stain called the Golgi stain.
它工作原理很特别
And it works in a very particular way.
它并不是对组织里面的所有细胞进行染色
Instead of staining all of the cells inside of a tissue,
而是只染对其中大约1%的细胞
it somehow only stains about one percent of them.
它清除了森林的图像,展现了其中的树木
It clears the forest, reveals the trees inside.
如果所有东西都被标记上的话,那什么都看不见了
If everything had been labeled, nothing would have been visible.
所有它以某种方式展示了大脑里的东西
So somehow it shows what’s there.
西班牙神经解剖学家圣地亚哥·拉蒙-卡哈尔
Spanish neuroanatomist Santiago Ramon y Cajal,
被普遍认为是现代神经科学之父
who’s widely considered the father of modern neuroscience,
他用高尔基染色法展示了这样的图像
applied this Golgi stain, which yields data which looks like this,
这给了我们神经细胞,神经元的现代概念
and really gave us the modern notion of the nerve cell, the neuron.
如果你把大脑想象成一个电脑
And if you’re thinking of the brain as a computer,
这就是晶体管
this is the transistor.
卡哈尔很快意识到
And very quickly Cajal realized
神经元不是单独工作的
that neurons don’t operate alone,
而是与其它神经元互相连接
but rather make connections with others
形成像电脑一样的电路
that form circuits just like in a computer.
今天,一个世纪之后,当研究人员想要看神经元的时候
Today, a century later, when researchers want to visualize neurons,
他们从内部点亮神经元,而不是让它们变暗
they light them up from the inside rather than darkening them.
它有几种做法
And there’s several ways of doing this.
最流行的做法之一
But one of the most popular ones
要用到荧光蛋白
involves green fluorescent protein.
现在,绿色荧光蛋白
Now green fluorescent protein,
一种来自生物发光的水母中的荧光蛋白
which oddly enough comes from a bioluminescent jellyfish,
很有用处
is very useful.
因为如果你能得到绿色荧光蛋白的基因
Because if you can get the gene for green fluorescent protein
并把它运入一个细胞
and deliver it to a cell,
那个细胞就会发出绿色荧光——
that cell will glow green —
如果你使用任何这种绿色荧光蛋白的变体
or any of the many variants now of green fluorescent protein,
你可以让一个细胞发出不同的颜色的荧光
you get a cell to glow many different colors.
回到大脑的话题
And so coming back to the brain,
有一种叫“大脑彩虹”的转基因小鼠
this is from a genetically engineered mouse called “Brainbow.”
人们这样叫它
And it’s so called, of course,
当然是因为这些神经元在发出不同颜色的荧光
because all of these neurons are glowing different colors.
现在,神经科学家们有时候需要识别
Now sometimes neuroscientists need to identify
神经元的特定分子元件
individual molecular components of neurons, molecules,
识别分子,而不是整个细胞
rather than the entire cell.
这可以通过好几种方法做到
And there’s several ways of doing this,
但是最流行的方法之一
but one of the most popular ones
用到了抗体
involves using antibodies.
你们一定
And you’re familiar, of course,
对作为免疫系统的抗体十分熟悉
with antibodies as the henchmen of the immune system.
实际上它们在免疫系统中如此重要的原因是
But it turns out that they’re so useful to the immune system
它们可以识别特定的分子
because they can recognize specific molecules,
比如一个入侵身体的病毒的
like, for example, the coat protein
外壳蛋白
of a virus that’s invading the body.
研究人员利用抗体的这个特性
And researchers have used this fact
来识别大脑内部的特定分子
in order to recognize specific molecules inside of the brain,
识别细胞的特定亚结构
recognize specific substructures of the cell
并将它们逐个分辨出来
and identify them individually.
我在这展示的很多图像都很漂亮
And a lot of the images I’ve been showing you here are very beautiful,
但它们同时也很强大
but they’re also very powerful.
它们可以解释很多东西
They have great explanatory power.
比如说,这是一个
This, for example, is an antibody staining
针对小鼠大脑切片里5-羟色胺转运体的抗体染色图象
against serotonin transporters in a slice of mouse brain.
你们肯定听说过5-羟色胺
And you’ve heard of serotonin, of course,
它与忧虑、焦虑一类的疾病有关
in the context of diseases like depression and anxiety.
你们也听说过 SSRIs (选择性5-羟色胺再摄取抑制剂)
You’ve heard of SSRIs,
它被用来治疗以上几种疾病
which are drugs that are used to treat these diseases.
如果想了解5-羟色胺是怎么起作用的
And in order to understand how serotonin works,
我们必须先明白5-羟色胺作用的部位在哪里
it’s critical to understand where the serontonin machinery is.
而我们可以通过这样的抗体染色
And antibody stainings like this one
来解答类似的问题
can be used to understand that sort of question.
我想给你们留下这样一个信息:
I’d like to leave you with the following thought:
绿色荧光蛋白和抗体
Green fluorescent protein and antibodies
最早都是自然产物
are both totally natural products at the get-go.
它们通过自然进化
They were evolved by nature
以便使一个水母不论以什么原因发出绿色荧光
in order to get a jellyfish to glow green for whatever reason,
或是以便识别入侵身体的病毒的外壳蛋白
or in order to detect the coat protein of an invading virus, for example.
过了很久很久以后,科学家才出场
And only much later did scientists come onto the scene
说:“这些都是工具,
and say, “Hey, these are tools,
我们可以把这些功能
these are functions that we could use
用到我们自己的研究工具控制板上。”
in our own research tool palette.”
与其用有限的人类智慧
And instead of applying feeble human minds
来从头设计工具
to designing these tools from scratch,
不如用这些在自然界中
there were these ready-made solutions right out there in nature
经过几百万年的发展、改善并稳定下来的现成的工具来解答
developed and refined steadily for millions of years
它们是大自然的鬼斧神工
by the greatest engineer of all.
谢谢
Thank you.
(掌声)
(Applause)

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https://www.youtube.com/watch?v=s4smjT1qwZU

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