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脑科学:光遗传学和扩张显微镜 – 译学馆
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脑科学:光遗传学和扩张显微镜

Brain Science: Optogenetics and Expansion Microscopy | Edward Boyden bigthink

大想法
big think
在过去的十年里
Over the last decade,
我们一直在努力构建工具
what we’ve been doing is trying to build tools
让我们观看和控制大脑的运作
that let us watch and control the operation of the brain.
举例来说 如果我们能像
If we can understand the brain
我们理解计算机那样理解大脑
the way that we understand computers,
也许我们能在如此详细的层次上
for example, maybe we could understand the brain
理解大脑
at such a level of detail,
你就能真正理解
that you could really comprehend
大脑是如何产生诸如
how it generates things like
思想 感觉 行动和感觉等事物的
thoughts and feelings, actions and sensations.
例如 我们开发的一种技术
For example, one technology that we’ve developed
被称为光遗传学
is called optogenetics.
我们通过光遗传学
In optogenetics, we install a gene
在大脑的一个或一组细胞中
that encodes for a light sensitive protein
编码一种含光敏蛋白的基因
in a cell or a set of cells in the brain.
然后我们可以
And then we can aim light at those cells,
用光纤
down an optical fiber,
或扫描激光瞄准那些细胞
or with a scanning laser.
这样你就可以对大脑进行控制了
So then you can play back activity to the brain.
例如 人们把人工感觉植入大脑
People have put artificial sensations into the brain.
你就能找出一种气味是如何表现的
Can you figure out how a smell is represented for example.
人们可以引发情绪
People can trigger emotions,
一些团体做了
and some groups have done
一些非常有趣的哲学实验
some pretty philosophically interesting experiments.
例如
So, for example,
加州理工大学的一个小组
a group at Cal Tech has activated certain clusters of cells,
激活了老鼠大脑深处的某些细胞群
deep, deep in the brains of mice.
如果正确的找到了这些细胞群
And if it’s the right cluster,
就可以让老鼠
you can actually trigger a mouse
变得好斗和暴力
to become aggressive or violent.
它们会攻击周围的一切东西
They’ll attack whatever’s next to them,
甚至是橡皮手套这一类的东西
even if it’s like a rubber glove, right?
你也可以研究疾病
You can also study diseases.
例如 你可以
You can, for example,
阻止癫痫发作中过度活跃的细胞
turn off overactive cells in a seizure.
然后你就能让癫痫动物实验样本
And you can actually shut down seizures
停止癫痫发作
in animal models with epilepsy.
这些技术主要用在动物身上
These technologies are mostly being used in animals
来揭示大脑回路是如何改变治疗效果的
to reveal how brain circuits might be changed for therapeutic benefit.
例如 我的小组和另一个小组合作
So, for example, my group collaborated with another group
找出某些大脑模式
to figure out that certain brain patterns
实际上有助于清除阿尔茨海默氏症的后遗症
actually might help clean up the debris in Alzheimer’s disease.
通过这些认识
From that knowledge,
你就可以去开发其他非侵入性的方案
you can then go and develop other non-invasive strategies
来帮助防止
to try to help prevent,
减少或逆转脑部疾病的影响
reduce the effects of or reverse brain disorders.
而且 一些人正在探索
However, some people are exploring
光遗传学是否可以直接用在人类身上
whether optogenetics might someday be used in humans directly.
其中引起人们极大兴趣的一个领域就是失明
And one area that’s of great interest is blindness.
数以百万计的人
Millions of people cannot see,
因为眼睛里的作为光感受器
because the photoreceptors in their eyes,
的感光细胞死亡而失明
the light capturing cells have died off.
如果你能把眼睛里的其余的备用细胞
If you could convert the rest of the eye into a camera though,
通过光遗传学工具
by installing the optogenetic tools
转化为成像细胞
in spared cells of the eye,
也许你就能帮助这些人复明了
maybe you could help these people see again.
我们开发的另一项技术
Another technology we’ve developed
可以让我们绘制大脑结构图
allows us to map the structure of the brain.
大脑非常致密复杂
The brain is really dense and complicated.
在你的大脑里 1立方毫米的地方
In a cubic millimeter of your brain,
就有大约100000个神经元细胞
you have around 100,000 cells called neurons,
而且它们是相互连接的
and they’re wired up.
它们的连接处叫做突触
They’re connected at junctions called synapses.
大脑里 1立方毫米的地方
And there are about a billion synapses
大约有十亿个突触
in that cubic millimeter.
所以绘制出大脑的连接方式
So mapping how the brain is wired up
是一项很艰巨的任务
is a truly daunting task.
在绘制线路图时需要纳米级的精度
How can you image such a complex 3D structure
所以很难想象如此复杂的3D结构该如何绘制
with the nanoscale precision required to map the wiring?
我们使用了一种非常规的方式
Well, we do it through a fairly unconventional way.
与过去300年前的成像不同
In contrast to the last 300 years of imaging
过去是用透镜放大样品的光
where you use a lens to magnify light coming from a sample,
而我们实际上取了脑的碎片
we actually take pieces of brain,
用化学药品把它们溶解
and fuse them with a chemical
这种药品很像婴儿尿布里的东西
that’s a lot like the stuff in baby diapers.
然后我们加水
And then we add water.
婴儿尿布的材料就会膨胀
The baby diaper material swells,
把大脑的这些碎片扩大100倍
and blows up the brain to make it 100 times
1000倍 甚至更大的体积
or 1,000 times or even more bigger by volume.
所以 因为我们用一种平稳的方式
So, because we move all the molecules
移动了所有的分子 使它们相互远离
away from each other in a smooth even fashion,
我们就可以绘制出它们间的连接机构
we can map their relative organization.
我的希望是如果我们能绘制出大脑的关键几何图形
My hope is if we can map out the key geometry of the brain,
以及分子是如何组织起来的
and how molecules are organized,
也许我们就可以模拟出大脑
maybe we could simulate a brain circuit,
处理事情时的脑回路 比如 做决定
while it’s doing something like constructing a decision,
感受事物 或执行动作
or sensing something, or performing an action.
这不是一个很好的比喻 但可以描绘出大脑的这种状况
It’s not a very good metaphor, but imagine of the brain.
你想像解决计算机问题一样
You’re trying to solve the brain
解决大脑问题
in the same way that you might solve a computer.
控制大脑就像控制计算机
You need to control the computer,
而光遗传学就是我们控制大脑的键盘
that’s the keyboard we use optogenetics.
我们之前用膨胀物得到的连接图
You need a map of the computer, the wiring,
就像是电脑的连接图
that’s what we’re using expansion across before.
同样 监控电脑的操作 需要用到显示器
And you need to watch the computer in action, the monitor.
而我们现在也在研究可以监控大脑的“显示器”
And we’re still working on those technologies currently.
我希望未来几年我们会完成这样的想法
I hope we’ll have that thought in the next couple of years.
但是如果你能把线路 监视和控制
But if you can put those three things together,
这三样东西放在一起
the wiring, the watching, and the control,
你就可以做很多解调
you can do a lot of interrogation
来看计算回路是如何工作的
at how computational circuits work.
BIGTHINK.COM
BIGTHINK.COM

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视频概述

利用光遗传学技术治疗失明,防止癫痫病发作,治疗阿尔茨海默病后遗症。利用扩张显微镜绘制大脑回路连接图,从而帮助人类改善治疗。

听录译者

红花老七

翻译译者

林邑

审核员

ZY

视频来源

https://www.youtube.com/watch?v=RTS6f0A5ifc

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