ABOUT THE SPEAKER
Ed Boyden - Neuroengineer
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute.

Why you should listen

Ed Boyden leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain. His group applies these tools in a systematic way in order to reveal ground truth scientific understandings of biological systems, which in turn reveal radical new approaches for curing diseases and repairing disabilities. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision, and optogenetic tools, which enable the activation and silencing of neural activity with light (TED Talk: A light switch for neurons). Boyden also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.

Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013) and the NIH Director's Pioneer Award (2013). He was also named to the World Economic Forum Young Scientist list (2013) and the Technology Review World's "Top 35 Innovators under Age 35" list (2006). His group has hosted hundreds of visitors to learn how to use new biotechnologies and spun out several companies to bring inventions out of his lab and into the world. Boyden received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents and articles, and he has given over 300 invited talks on his group's work.

More profile about the speaker
Ed Boyden | Speaker | TED.com
TED2011

Ed Boyden: A light switch for neurons

Ed Boyden: Un interruptor para neuronas

Filmed:
1,098,379 views

Ed Boyden amósamos como, inserindo xenes con proteínas sensibles á luz en células cerebrais, pode activar ou desactivar selectivamente neuronas específicas con implantes de fibra óptica. Con este nivel de control sen precedentes, é capaz de curar ratos con trastornos similares ao estrés postraumático e certas formas de cegueira. No horizonte: próteses neurais. O presentador da sesión, Juan Enríquez, lidera unha breve charla final de preguntas e respostas.
- Neuroengineer
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute. Full bio

Double-click the English transcript below to play the video.

00:15
Think about your day for a second.
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Pensen no seu día por un segundo.
00:17
You woke up, felt fresh air on your face as you walked out the door,
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Espertaron, sentiron o aire fresco
na cara ao saír pola porta,
00:20
encountered new colleagues and had great discussions,
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atoparon novos colegas
e tiveron bos debates,
00:22
and felt in awe when you found something new.
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e asombráronse ao atopar algo novo.
00:24
But I bet there's something you didn't think about today --
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Pero aposto a que hoxe non pensaron
00:26
something so close to home
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en algo tan próximo a nós
00:28
that you probably don't think about it very often at all.
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que non atrae a nosa atención moi a miúdo.
00:30
And that's that all the sensations, feelings,
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Que todas esas sensacións, sentimentos,
00:32
decisions and actions
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decisións e accións
00:34
are mediated by the computer in your head
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son intermediadas
por unha computadora na súa cabeza
00:36
called the brain.
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á que chamamos cerebro.
00:38
Now the brain may not look like much from the outside --
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E pode non parecer gran cousa dende fóra:
00:40
a couple pounds of pinkish-gray flesh,
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un quilo de carne de cor gris rosácea,
00:42
amorphous --
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amorfa,
00:44
but the last hundred years of neuroscience
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pero os últimos cen anos de neurociencia
00:46
have allowed us to zoom in on the brain,
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permitíronnos entrar no cerebro
00:48
and to see the intricacy of what lies within.
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e ve-la complexidade do seu interior.
00:50
And they've told us that this brain
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E dixéronnos que este cerebro
00:52
is an incredibly complicated circuit
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é un circuíto incriblemente complicado
00:54
made out of hundreds of billions of cells called neurons.
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composto de centos de miles de millóns
de células chamadas neuronas.
00:58
Now unlike a human-designed computer,
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Agora ben, ao contrario dunha computadora
deseñada por humanos
con moitas menos pezas distintas
01:01
where there's a fairly small number of different parts --
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01:03
we know how they work, because we humans designed them --
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--sabemos como funcionan,
posto que as deseñamos nos--
01:06
the brain is made out of thousands of different kinds of cells,
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o cerebro está composto
de miles de tipos diferentes de células,
01:09
maybe tens of thousands.
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quizais decenas de miles.
De distintas formas, a partir de
moléculas diversas,
01:11
They come in different shapes; they're made out of different molecules.
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01:13
And they project and connect to different brain regions,
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e que proxectan e conectan
cara a distintas rexións do cerebro.
01:16
and they also change different ways in different disease states.
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E tamén cambian nos diferentes estadios
da enfermidade.
01:19
Let's make it concrete.
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Sexamos máis concretos.
01:21
There's a class of cells,
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Temos unha clase de células,
unha célula moi pequena, inhibidora,
que silencia as súas veciñas.
01:23
a fairly small cell, an inhibitory cell, that quiets its neighbors.
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01:26
It's one of the cells that seems to be atrophied in disorders like schizophrenia.
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É unha das células que se atrofiaría en
trastornos como a esquizofrenia.
01:30
It's called the basket cell.
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É coñecida coma célula cesta;
01:32
And this cell is one of the thousands of kinds of cell
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E é un dos miles de tipos de células
01:34
that we are learning about.
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acerca das cales estamos aprendendo.
01:36
New ones are being discovered everyday.
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Descóbrense novos tipos tódolos días.
01:38
As just a second example:
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Só un segundo exemplo:
01:40
these pyramidal cells, large cells,
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estas células piramidais, grandes células,
01:42
they can span a significant fraction of the brain.
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que abarcan unha parte importante
do cerebro.
01:44
They're excitatory.
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Son excitatorias.
01:46
And these are some of the cells
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E estas son algunhas das células
01:48
that might be overactive in disorders such as epilepsy.
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que poderían estar hiperactivas
en trastornos como a epilepsia.
01:51
Every one of these cells
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Cada unha destas células
01:53
is an incredible electrical device.
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é un dispositivo eléctrico incrible.
01:56
They receive input from thousands of upstream partners
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Reciben sinais de miles de células
da parte superior
01:58
and compute their own electrical outputs,
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e calculan as súas propias
respostas eléctricas
02:01
which then, if they pass a certain threshold,
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que ao superar un determinado límite,
pasarán a miles de células
da parte inferior.
02:03
will go to thousands of downstream partners.
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02:05
And this process, which takes just a millisecond or so,
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E este proceso, que leva só
un milisegundo máis ou menos,
02:08
happens thousands of times a minute
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sucede miles de veces por minuto
02:10
in every one of your 100 billion cells,
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para cada unha
das 100 mil millóns de células,
02:12
as long as you live
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mentres vostedes viven,
02:14
and think and feel.
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e pensan e senten.
02:17
So how are we going to figure out what this circuit does?
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Así pois, como imos descifrar
qué fai este circuíto?
02:20
Ideally, we could go through the circuit
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O ideal sería ir a través del
02:22
and turn these different kinds of cell on and off
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e acender e apaga-los distintos
tipos de células
02:25
and see whether we could figure out
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e ver se podemos esclarecer
02:27
which ones contribute to certain functions
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cales contribúen a determinadas funcións
02:29
and which ones go wrong in certain pathologies.
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e cales funcionan mal
en certas patoloxías.
02:31
If we could activate cells, we could see what powers they can unleash,
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Se puideramos activalas poderíamos
ver qué potencial liberan,
02:34
what they can initiate and sustain.
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e qué poden iniciar e manter.
02:36
If we could turn them off,
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Se puideramos apagalas, entón
poderíamos tentar ver
para que son precisas.
02:38
then we could try and figure out what they're necessary for.
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02:40
And that's a story I'm going to tell you about today.
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E esa é unha historia
que lles vou contar hoxe.
02:43
And honestly, where we've gone through over the last 11 years,
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E, honestamente, por onde pasamos
nos últimos 11 anos
02:46
through an attempt to find ways
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na busca de maneiras
02:48
of turning circuits and cells and parts and pathways of the brain
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de acender e apagar circuítos e células
02:50
on and off,
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e rutas do cerebro,
02:52
both to understand the science
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tanto para entende-la ciencia,
02:54
and also to confront some of the issues
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como para facerlles fronte
a algúns dos problemas
02:57
that face us all as humans.
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cos que todos batemos como humanos.
03:00
Now before I tell you about the technology,
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Pero antes de falarlles da tecnoloxía,
03:03
the bad news is that a significant fraction of us in this room,
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a mala nova é que unha parte
significativa de nós nesta sala,
03:06
if we live long enough,
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se vivímo-lo suficiente,
03:08
will encounter, perhaps, a brain disorder.
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probablemente suframos
un trastorno cerebral.
03:10
Already, a billion people
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Xa mil millóns de persoas
03:12
have had some kind of brain disorder
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tiveron algún tipo de trastorno cerebral
03:14
that incapacitates them,
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que as incapacita,
e, porén, as cifras non lle fan xustiza.
03:16
and the numbers don't do it justice though.
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03:18
These disorders -- schizophrenia, Alzheimer's,
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Estes trastornos
--a esquizofrenia, o alzheimer,
03:20
depression, addiction --
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a depresión, a adicción--
03:22
they not only steal our time to live, they change who we are.
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non só nos rouban tempo de vida,
cambian o noso ser.
03:25
They take our identity and change our emotions
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Quítannos a nosa identidade e cambian
as nosas emocións
03:27
and change who we are as people.
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e cambian o que somos como persoas.
03:30
Now in the 20th century,
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Agora ben, no século XX
03:33
there was some hope that was generated
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xerouse algo de esperanza
03:36
through the development of pharmaceuticals for treating brain disorders,
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grazas ao desenvolvemento de fármacos
para trastornos cerebrais.
03:39
and while many drugs have been developed
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E aínda que se desenvolveron
moitas medicinas
que poden alivia-los síntomas
deses trastornos,
03:42
that can alleviate symptoms of brain disorders,
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03:44
practically none of them can be considered to be cured.
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na práctica ningún deles pode
considerarse curable.
03:47
And part of that's because we're bathing the brain in the chemical.
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En parte porque estamos inundando
o cerebro con química.
03:50
This elaborate circuit
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Este elaborado circuíto
composto de miles
de tipos de células diferentes
03:52
made out of thousands of different kinds of cell
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03:54
is being bathed in a substance.
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está sendo bañado nunha substancia.
Por iso, a maior parte das medicinas
03:56
That's also why, perhaps, most of the drugs, and not all, on the market
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03:58
can present some kind of serious side effect too.
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pode presentar algún tipo
de efecto secundario importante.
04:01
Now some people have gotten some solace
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Agora, algunhas persoas recibiron
algún consolo
04:04
from electrical stimulators that are implanted in the brain.
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de estimuladores eléctricos
que se implantan no cerebro.
04:07
And for Parkinson's disease,
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E para o párkinson,
04:09
Cochlear implants,
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os implantes cocleares,
04:11
these have indeed been able
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foron capaces
04:13
to bring some kind of remedy
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de fornecer algún alivio
a persoas con certos tipos de trastornos.
04:15
to people with certain kinds of disorder.
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04:17
But electricity also will go in all directions --
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Pero a electricidade
tamén irá cara a todas partes
04:19
the path of least resistance,
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pola ruta de menor resistencia,
04:21
which is where that phrase, in part, comes from.
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e de aí, en parte, vén esta expresión.
04:23
And it also will affect normal circuits as well as the abnormal ones that you want to fix.
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E isto afectará aos circuítos normais
pero tamén aos que queremos corrixir.
04:26
So again, we're sent back to the idea
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Así que de novo, volvemos á idea
04:28
of ultra-precise control.
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do control ultrapreciso.
04:30
Could we dial-in information precisely where we want it to go?
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Podemos dirixi-la información exactamente
cara a onde queremos?
04:34
So when I started in neuroscience 11 years ago,
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Cando comecei na neurociencia hai 11 anos
04:38
I had trained as an electrical engineer and a physicist,
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formárame como enxeñeiro eléctrico
e como físico,
04:41
and the first thing I thought about was,
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e o primeiro que pensei foi:
se as neuronas son dispositivos eléctricos
04:43
if these neurons are electrical devices,
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04:45
all we need to do is to find some way
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todo o que fai falla é atopa-lo modo
de manexar a distancia
eses cambios eléctricos.
04:47
of driving those electrical changes at a distance.
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04:49
If we could turn on the electricity in one cell,
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Se puideramos acende-la electricidade
nunha célula,
04:51
but not its neighbors,
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pero non nas veciñas,
iso daríanos o que necesitamos para
activar e apaga-las células,
04:53
that would give us the tool we need to activate and shut down these different cells,
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04:56
figure out what they do and how they contribute
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para descubrir que fan e como contribúen
04:58
to the networks in which they're embedded.
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ás redes nas que están inseridas.
E tamén nos permitiría
o control ultrapreciso
05:00
And also it would allow us to have the ultra-precise control we need
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05:02
in order to fix the circuit computations
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necesario para corrixi-los cálculos
do circuíto
05:05
that have gone awry.
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que estiveran mal.
05:07
Now how are we going to do that?
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Agora, como imos facer iso?
05:09
Well there are many molecules that exist in nature,
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Ben, na natureza haiche moitas moléculas
05:11
which are able to convert light into electricity.
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capaces de converte-la luz
en electricidade.
05:14
You can think of them as little proteins
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Imaxínenas como pequenas proteínas
05:16
that are like solar cells.
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que son como celas fotovoltaicas.
05:18
If we can install these molecules in neurons somehow,
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Se, dalgún xeito, podemos instalar estas
moléculas nas neuronas
05:21
then these neurons would become electrically drivable with light.
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entón estas neuronas poderían
manipularse electricamente coa luz.
05:24
And their neighbors, which don't have the molecule, would not.
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E as súas veciñas,
que non teñen a molécula, non.
05:27
There's one other magic trick you need to make this all happen,
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Cómprenos outro truco de maxia
para que isto suceda:
05:29
and that's the ability to get light into the brain.
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a capacidade de meter luz no cerebro.
05:32
And to do that -- the brain doesn't feel pain -- you can put --
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E para logralo --o cerebro non sente dor--
pódese poñer
05:35
taking advantage of all the effort
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--aproveitando o esforzo
investido en Internet,
comunicacións, etc--
05:37
that's gone into the Internet and communications and so on --
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05:39
optical fibers connected to lasers
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fibra óptica conectada a láseres
que pode usarse para activar,
por exemplo en modelos animais,
05:41
that you can use to activate, in animal models for example,
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05:43
in pre-clinical studies,
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en estudios preclínicos,
05:45
these neurons and to see what they do.
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estas neuronas e ver qué fan.
05:47
So how do we do this?
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Entón, como o facemos?
05:49
Around 2004,
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Arredor de 2004,
en colaboración con Gerhard Nagel
e Karl Deisseroth
05:51
in collaboration with Gerhard Nagel and Karl Deisseroth,
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05:53
this vision came to fruition.
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esta visión fíxose realidade.
05:55
There's a certain alga that swims in the wild,
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Hai unha alga que nada no mundo silvestre
05:58
and it needs to navigate towards light
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e que ten que navegar cara á luz
06:00
in order to photosynthesize optimally.
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para face-la fotosíntese de forma óptima.
06:02
And it senses light with a little eye-spot,
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E detecta a luz cun pequeno ocelo
06:04
which works not unlike how our eye works.
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que funciona non moi distinto
ca os nosos ollos.
06:07
In its membrane, or its boundary,
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Na súa membrana, ou no seu bordo,
06:09
it contains little proteins
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contén pequenas proteínas
06:12
that indeed can convert light into electricity.
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que, de feito, poden converte-la luz
en electricidade.
06:15
So these molecules are called channelrhodopsins.
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Estas moléculas denomínanse
canalrodopsinas.
06:18
And each of these proteins acts just like that solar cell that I told you about.
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E cada unha actúa como esa cela
fotovoltaica da que falei.
06:21
When blue light hits it, it opens up a little hole
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Ante a presenza de luz azul,
abre un pequeno orificio
06:24
and allows charged particles to enter the eye-spot,
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que deixa pasar partículas cargadas
ao ocelo.
06:26
and that allows this eye-spot to have an electrical signal
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o que lle permite ter un sinal eléctrico
06:28
just like a solar cell charging up a battery.
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como unha cela fotovoltaica
que carga unha batería.
06:31
So what we need to do is to take these molecules
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Daquela,temos que toma-las moléculas
06:33
and somehow install them in neurons.
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e poñelas dalgún xeito nas neuronas.
06:35
And because it's a protein,
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E dado que é unha proteína,
está codificada no ADN deste organismo.
06:37
it's encoded for in the DNA of this organism.
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06:40
So all we've got to do is take that DNA,
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Así que o que temos que facer é
toma-lo ADN,
06:42
put it into a gene therapy vector, like a virus,
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colocalo nun vector de terapia xénica,
coma un virus,
06:45
and put it into neurons.
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E poñelo nas neuronas.
06:48
So it turned out that this was a very productive time in gene therapy,
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Resultou ser un momento moi produtivo
en terapia xénica,
06:51
and lots of viruses were coming along.
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e empezaron a aparecer moitos virus.
06:53
So this turned out to be very simple to do.
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Así que resultou moi simple de facer.
06:55
And early in the morning one day in the summer of 2004,
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E unha mañanciña do verán de 2004
tentámolo e funcionou á primeira.
06:58
we gave it a try, and it worked on the first try.
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07:00
You take this DNA and you put it into a neuron.
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Tómase este ADN e colócase nunha neurona.
07:03
The neuron uses its natural protein-making machinery
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A neurona usa o seu mecanismo natural
de elaboración de proteínas
07:06
to fabricate these little light-sensitive proteins
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para facer pequenas proteínas
fotosensibles
07:08
and install them all over the cell,
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e colocalas por toda a célula,
07:10
like putting solar panels on a roof,
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como paneis solares nun tellado,
07:12
and the next thing you know,
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e o seguinte que sabemos
é que temos unha neurona
activable por luz.
07:14
you have a neuron which can be activated with light.
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07:16
So this is very powerful.
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E isto é moi valioso.
07:18
One of the tricks you have to do
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Un dos trucos que tes que facer
é atopar como leva-los xenes
ás células que queres
07:20
is to figure out how to deliver these genes to the cells that you want
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07:22
and not all the other neighbors.
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E non a tódalas súas veciñas.
07:24
And you can do that; you can tweak the viruses
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E pode facerse; pódese axusta-lo virus
para que acade unhas células e non outras.
07:26
so they hit just some cells and not others.
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07:28
And there's other genetic tricks you can play
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E hai outros trucos xenéticos
aos que recorrer
07:30
in order to get light-activated cells.
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co fin de obter células fotoactivadas.
07:33
This field has now come to be known as optogenetics.
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Este campo coñécese como optoxenética.
E, como exemplo de cousas
que se poden facer,
07:37
And just as one example of the kind of thing you can do,
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07:39
you can take a complex network,
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podes tomar unha rede complexa,
07:41
use one of these viruses to deliver the gene
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usar un destes virus para entrega-lo xene
07:43
just to one kind of cell in this dense network.
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a un só tipo de célula nesta densa rede.
07:46
And then when you shine light on the entire network,
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E despois cando a luz ilumina toda a rede
07:48
just that cell type will be activated.
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só se activará ese tipo de célula.
07:50
So for example, lets sort of consider that basket cell I told you about earlier --
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Por exemplo, pensemos nesa célula
cesta que lles mencionei antes,
07:53
the one that's atrophied in schizophrenia
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a que se atrofia na esquizofrenia
07:55
and the one that is inhibitory.
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e que é inhibitoria.
07:57
If we can deliver that gene to these cells --
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Se podemos levar ese xene a esas células
07:59
and they're not going to be altered by the expression of the gene, of course --
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e que non se vexan alteradas pola
expresión dese xene, por suposto,
08:02
and then flash blue light over the entire brain network,
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e despois iluminamos de azul
toda a rede cerebral
08:05
just these cells are going to be driven.
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só se verán afectadas esas células.
08:07
And when the light turns off, these cells go back to normal,
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E cando apagamos a luz as células
volven á normalidade,
08:09
so they don't seem to be averse against that.
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así que iso non parece afectalas
.
08:12
Not only can you use this to study what these cells do,
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Non só se usa para estuda-lo
funcionamento celular,
08:14
what their power is in computing in the brain,
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o seu poder de cómputo no cerebro,
08:16
but you can also use this to try to figure out --
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senón tamén para tratar de descubrir
08:18
well maybe we could jazz up the activity of these cells,
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se poderiamos animar
a actividade desas células
08:20
if indeed they're atrophied.
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se realmente están atrofiadas.
08:22
Now I want to tell you a couple of short stories
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Agora quero contarlles
un par de historias breves
08:24
about how we're using this,
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acerca do uso que facemos disto,
08:26
both at the scientific, clinical and pre-clinical levels.
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a nivel científico, clínico e preclínico.
08:29
One of the questions we've confronted
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Unha das preguntas a que nos enfrontamos é
08:31
is, what are the signals in the brain that mediate the sensation of reward?
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cales son os sinais cerebrais implicados
na sensación de recompensa?
08:34
Because if you could find those,
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Porque se puideramos atopalos
serían os sinais que poderían
guia-la aprendizaxe.
08:36
those would be some of the signals that could drive learning.
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08:38
The brain will do more of whatever got that reward.
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O cerebro repetirá o que o gratifica.
08:40
And also these are signals that go awry in disorders such as addiction.
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E ademais, estes sinais funcionan mal
nos trastornos adictivos.
08:43
So if we could figure out what cells they are,
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Así, se descubrísemos esas células
08:45
we could maybe find new targets
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quizais poderiamos atopar novas dianas
08:47
for which drugs could be designed or screened against,
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para as que deseñar
ou probar medicamentos,
08:49
or maybe places where electrodes could be put in
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ou quizais lugares
nos que colocar eléctrodos
08:51
for people who have very severe disability.
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para persoas con discapacidades
moi graves.
08:54
So to do that, we came up with a very simple paradigm
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Para isto, ocorréusenos
un paradigma moi simple
08:56
in collaboration with the Fiorella group,
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en colaboración co grupo Fiorella,
08:58
where one side of this little box,
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nun lado desta pequena caixa,
09:00
if the animal goes there, the animal gets a pulse of light
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se o animal vai alí,
recibe un pulso de luz
09:02
in order to make different cells in the brain sensitive to light.
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que fará fotosensibles
varias células cerebrais.
09:04
So if these cells can mediate reward,
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Así, se estas células
participan na recompensa,
09:06
the animal should go there more and more.
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o animal debería ir alí cada vez máis.
09:08
And so that's what happens.
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Iso é o que sucede.
O animal vai ir mete-lo nariz
ao lado dereito
09:10
This animal's going to go to the right-hand side and poke his nose there,
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09:12
and he gets a flash of blue light every time he does that.
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e cada vez que o fai recibe un
flash azul.
09:14
And he'll do that hundreds and hundreds of times.
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E farao centos e centos de veces.
09:16
These are the dopamine neurons,
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Son as neuronas dopamina,
que como saberán, participan
dos centros cerebrais do pracer.
09:18
which some of you may have heard about, in some of the pleasure centers in the brain.
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09:20
Now we've shown that a brief activation of these
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Demostramos que activalas brevemente
09:22
is enough, indeed, to drive learning.
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é suficiente para guia-la aprendizaxe.
09:24
Now we can generalize the idea.
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Podemos xeneraliza-la idea.
09:26
Instead of one point in the brain,
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En lugar de un só punto no cerebro
09:28
we can devise devices that span the brain,
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podemos idear dispositivos
para todo o cerebro,
09:30
that can deliver light into three-dimensional patterns --
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que leven a luz en patróns tridimensionais
09:32
arrays of optical fibers,
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--matrices de fibra óptica,
09:34
each coupled to its own independent miniature light source.
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cunha minifonte luminosa independente.
09:36
And then we can try to do things in vivo
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E podemos tratar de facer en vivo
09:38
that have only been done to-date in a dish --
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o que, ata o momento,
se fixo só nunha placa,
09:41
like high-throughput screening throughout the entire brain
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como a visualización completa do cerebro
para sinais que fan
que sucedan certas cousas.
09:43
for the signals that can cause certain things to happen.
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09:45
Or that could be good clinical targets
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Ou poderían ser bos obxectivos clínicos
09:47
for treating brain disorders.
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para o tratamento de trastornos cerebrais.
09:49
And one story I want to tell you about
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E outra historia que quero contarlles
09:51
is how can we find targets for treating post-traumatic stress disorder --
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é como atopamos dianas para trata-lo
estrés postraumático,
09:54
a form of uncontrolled anxiety and fear.
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unha forma de ansiedade
e medo descontrolados.
09:57
And one of the things that we did
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E unha das cousas que fixemos
09:59
was to adopt a very classical model of fear.
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foi adopta-lo modelo máis clásico do medo.
10:02
This goes back to the Pavlovian days.
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Remóntase aos días de Pavlov.
10:05
It's called Pavlovian fear conditioning --
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Denomínase medo condicionado pavloviano,
10:07
where a tone ends with a brief shock.
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e nel un ton remata cunha breve descarga.
10:09
The shock isn't painful, but it's a little annoying.
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A descarga non doe, pero molesta un pouco.
10:11
And over time -- in this case, a mouse,
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E co tempo --un rato,
un bo modelo animal,
usado a miúdo en experimentos,
10:13
which is a good animal model, commonly used in such experiments --
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10:15
the animal learns to fear the tone.
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aprende a temerlle ao ton.
10:17
The animal will react by freezing,
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O animal reaccionará paralizándose,
10:19
sort of like a deer in the headlights.
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coma un cervo diante dos faros.
10:21
Now the question is, what targets in the brain can we find
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Agora, a pregunta é, que dianas
podemos atopar no cerebro
10:24
that allow us to overcome this fear?
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que nos permitan superar ese temor?
10:26
So what we do is we play that tone again
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Para iso reproducimos o ton novamente
10:28
after it's been associated with fear.
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despois de que se asocie co medo.
10:30
But we activate targets in the brain, different ones,
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Pero activamos novas dianas no cerebro,
10:32
using that optical fiber array I told you about in the previous slide,
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usando esa matriz de fibra óptica
que lles mostrei antes
10:35
in order to try and figure out which targets
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para tratar de desvelar qué dianas
10:37
can cause the brain to overcome that memory of fear.
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poden facer que o cerebro supere
esa memoria do medo.
10:40
And so this brief video
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Este breve vídeo
mostra unha das dianas
con que traballamos.
10:42
shows you one of these targets that we're working on now.
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10:44
This is an area in the prefrontal cortex,
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Unha área do córtex prefrontal,
unha rexión
10:46
a region where we can use cognition to try to overcome aversive emotional states.
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na que pode usarse a cognición para
superar estados aversivos.
10:49
And the animal's going to hear a tone -- and a flash of light occurred there.
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Cando o animal oe un ton,
aparece un flash.
10:51
There's no audio on this, but you can see the animal's freezing.
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Non o oen, pero ven
que o rato se paraliza.
10:53
This tone used to mean bad news.
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O ton adoitaba representar malas noticias.
10:55
And there's a little clock in the lower left-hand corner,
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Hai un reloxo na esquina inferior esquerda
10:57
so you can see the animal is about two minutes into this.
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para que poidan ver que o animal
queda así uns 2 minutos.
11:00
And now this next clip
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E agora, o seguinte vídeo,
11:02
is just eight minutes later.
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de só 8 minutos despois.
11:04
And the same tone is going to play, and the light is going to flash again.
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Vaise reproduci-lo ton, e a luz
dispárase outra vez.
11:07
Okay, there it goes. Right now.
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Ben, aí vai. Xusto agora.
11:10
And now you can see, just 10 minutes into the experiment,
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E agora poden ver,
en só 10 minutos de experimento,
11:13
that we've equipped the brain by photoactivating this area
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que preparamos o cerebro,
fotoactivando esta zona,
11:16
to overcome the expression
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para supera-la expresión
11:18
of this fear memory.
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desta memoria do medo.
11:20
Now over the last couple of years, we've gone back to the tree of life
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Durante os últimos dous anos,
volvemos atrás na árbore da vida
11:23
because we wanted to find ways to turn circuits in the brain off.
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porque queriamos atopar modos de
apaga-los circuítos cerebrais.
11:26
If we could do that, this could be extremely powerful.
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Se puideramos facelo sería
algo moi poderoso.
11:29
If you can delete cells just for a few milliseconds or seconds,
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Se podes suprimir células
durante uns milisegundos ou segundos,
11:32
you can figure out what necessary role they play
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podes darte de conta da súa relevancia
11:34
in the circuits in which they're embedded.
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nos circuítos en que están inseridas.
11:36
And we've now surveyed organisms from all over the tree of life --
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E estudamos toda a árbore da vida,
seres de tódolos reinos salvo o animal,
que é levemente distinto.
11:38
every kingdom of life except for animals, we see slightly differently.
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11:41
And we found all sorts of molecules, they're called halorhodopsins or archaerhodopsins,
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E atopamos moléculas chamadas
halorrodopsinas ou arqueorrodopsinas,
11:44
that respond to green and yellow light.
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que responden á luz verde e amarela.
11:46
And they do the opposite thing of the molecule I told you about before
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E que fan o oposto da molécula anterior,
11:48
with the blue light activator channelrhodopsin.
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a do activador de luz azul,
a canalrodopsina.
11:52
Let's give an example of where we think this is going to go.
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Vexamos un exemplo de cara a onde
pensamos que vai isto.
11:55
Consider, for example, a condition like epilepsy,
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Consideren, por exemplo, unha doenza
como a epilepsia,
11:58
where the brain is overactive.
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na que o cerebro é hiperactivo.
12:00
Now if drugs fail in epileptic treatment,
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Se falla a medicación
no tratamento da epilepsia,
12:02
one of the strategies is to remove part of the brain.
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pode eliminarse parte do cerebro.
12:04
But that's obviously irreversible, and there could be side effects.
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Pero isto é irreversible e ten
efectos secundarios.
12:06
What if we could just turn off that brain for a brief amount of time,
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Que pasaría se puideramos apaga-lo
cerebro por un breve instante
12:09
until the seizure dies away,
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ata que o ataque esvaecera
e facer que o cerebro volvera
ao seu estado inicial?
12:12
and cause the brain to be restored to its initial state --
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12:15
sort of like a dynamical system that's being coaxed down into a stable state.
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Algo así coma un sistema dinámico
dirixido cara a un estado estable.
12:18
So this animation just tries to explain this concept
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Esta animación tenta
explicar este concepto
12:21
where we made these cells sensitive to being turned off with light,
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onde creamos células
sensibles a desactivarse coa luz,
12:23
and we beam light in,
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e enfocámo-la luz sobre elas,
12:25
and just for the time it takes to shut down a seizure,
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e só durante o tempo que dura a convulsión
12:27
we're hoping to be able to turn it off.
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esperamos ser capaces de apagalas.
12:29
And so we don't have data to show you on this front,
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Non temos datos para amosar neste campo,
12:31
but we're very excited about this.
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pero estamos moi ilusionados.
12:33
Now I want to close on one story,
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Agora quero rematar cunha historia,
12:35
which we think is another possibility --
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que nos parece outra posibilidade
12:37
which is that maybe these molecules, if you can do ultra-precise control,
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e que, se acadamos
un control ultrapreciso,
12:39
can be used in the brain itself
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talvez permita usar
estas moléculas no propio cerebro
12:41
to make a new kind of prosthetic, an optical prosthetic.
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para facer un novo tipo de prótese óptica.
12:44
I already told you that electrical stimulators are not uncommon.
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Xa dixen que os estimuladores
eléctricos son comúns hoxe.
12:47
Seventy-five thousand people have Parkinson's deep-brain stimulators implanted.
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75 mil persoas teñen estimuladores
cerebrais para o párkinson.
12:50
Maybe 100,000 people have Cochlear implants,
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Talvez 100 mil teñan implantes cocleares,
12:52
which allow them to hear.
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que lles permiten oír.
12:54
There's another thing, which is you've got to get these genes into cells.
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Outra cosa é que temos que meter
eses xenes nas células.
12:57
And new hope in gene therapy has been developed
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E xurdiu unha nova esperanza en
terapia xénica
13:00
because viruses like the adeno-associated virus,
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grazas a virus como o virus adenoasociado,
13:02
which probably most of us around this room have,
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que probablemente
a maioría de vostedes terá
13:04
and it doesn't have any symptoms,
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sen presentar síntomas,
13:06
which have been used in hundreds of patients
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e que se empregou en centos de pacientes
13:08
to deliver genes into the brain or the body.
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para repartir xenes no cerebro e no corpo.
13:10
And so far, there have not been serious adverse events
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E, ata o de agora, non houbo
efectos adversos graves
13:12
associated with the virus.
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asociados co virus.
13:14
There's one last elephant in the room, the proteins themselves,
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Tamén adoitamos ignorar
outro gran problema: as propias proteínas,
13:17
which come from algae and bacteria and fungi,
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procedentes de algas, bacterias e fungos,
13:19
and all over the tree of life.
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e toda a árbore da vida.
13:21
Most of us don't have fungi or algae in our brains,
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A maioría non temos fungos nin algas
no cerebro,
13:23
so what is our brain going to do if we put that in?
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así que, que fará o cerebro se llas
inserimos?
13:25
Are the cells going to tolerate it? Will the immune system react?
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Tolerarano as células?
E o sistema inmunolóxico?
13:27
In its early days -- these have not been done on humans yet --
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Estamos comezando,
non se probou en humanos
13:29
but we're working on a variety of studies
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pero estamos a traballar en varios estudos
13:31
to try and examine this,
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tratando de examinalo,
13:33
and so far we haven't seen overt reactions of any severity
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e, ata o de agora, non atopamos
reaccións graves
13:36
to these molecules
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cara a estas moléculas
13:38
or to the illumination of the brain with light.
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ou cara á iluminación do cerebro con luz.
13:41
So it's early days, to be upfront, but we're excited about it.
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Sinceramente, estamos comezando
pero estamos entusiasmados.
13:44
I wanted to close with one story,
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Quero rematar cunha historia,
13:46
which we think could potentially
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que, cremos, podería
13:48
be a clinical application.
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ser unha aplicación clínica.
13:50
Now there are many forms of blindness
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Hoxe en día hai moitas formas de cegueira
13:52
where the photoreceptors,
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nas que os fotorreceptores,
13:54
our light sensors that are in the back of our eye, are gone.
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3000
os sensores de luz que están
no fondo do ollo, non funcionan.
13:57
And the retina, of course, is a complex structure.
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E a retina é unha estrutura complexa.
13:59
Now let's zoom in on it here, so we can see it in more detail.
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Agora ampliémolo, para velo mellor.
14:01
The photoreceptor cells are shown here at the top,
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As células fotorreceptoras
amósanse aquí arriba
14:04
and then the signals that are detected by the photoreceptors
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e os sinais detectados por elas
14:06
are transformed by various computations
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son transformados por varios cálculos
14:08
until finally that layer of cells at the bottom, the ganglion cells,
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ata que, ao final, a capa de células
ganglionares de abaixo
14:11
relay the information to the brain,
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transmite a información ao cerebro,
14:13
where we see that as perception.
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onde vemos iso como percepción.
14:15
In many forms of blindness, like retinitis pigmentosa,
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En moitas formas de cegueira,
como a retinite pigmentosa,
14:18
or macular degeneration,
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ou a dexeneración macular,
14:20
the photoreceptor cells have atrophied or been destroyed.
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as células fotorreceptoras
atrofiáronse ou destruíronse.
14:23
Now how could you repair this?
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Como arranxar isto?
14:25
It's not even clear that a drug could cause this to be restored,
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Nin sequera está claro
que un fármaco poida facelo
14:28
because there's nothing for the drug to bind to.
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porque non ten nada ao que ligarse.
14:30
On the other hand, light can still get into the eye.
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Por outra banda, a luz
aínda pode entrar no ollo.
14:32
The eye is still transparent and you can get light in.
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O ollo aínda é transparente
e permite o paso da luz.
14:35
So what if we could just take these channelrhodopsins and other molecules
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Así que, e se collemos
as canalrodopsinas e outras moléculas
14:38
and install them on some of these other spare cells
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e as poñemos nalgunha destoutras
células libres
14:40
and convert them into little cameras.
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e as convertemos en pequenas cámaras?
14:42
And because there's so many of these cells in the eye,
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E, xa que hai moitas
destas células no ollo,
14:44
potentially, they could be very high-resolution cameras.
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potencialmente, poderían ser cámaras
de moi alta definición.
14:47
So this is some work that we're doing.
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Velaquí o noso traballo en curso.
14:49
It's being led by one of our collaborators,
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Está dirixido por un
dos nosos colaboradores,
14:51
Alan Horsager at USC,
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Alan Horsager na USC,
14:53
and being sought to be commercialized by a start-up company Eos Neuroscience,
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e procuramos que sexa comercializado
por unha empresa nova,
14:56
which is funded by the NIH.
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Eos Neuroscience, financiada polo NIH.
14:58
And what you see here is a mouse trying to solve a maze.
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Aquí vemos un rato tentando
saír dun labirinto.
15:00
It's a six-arm maze. And there's a bit of water in the maze
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É un labirinto de 6 brazos con auga
para que o rato se mova
e non quede sentado.
15:02
to motivate the mouse to move, or he'll just sit there.
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15:04
And the goal, of course, of this maze
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O obxectivo deste labirinto, por suposto,
15:06
is to get out of the water and go to a little platform
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é saír da auga e subir a unha plataforma
15:08
that's under the lit top port.
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baixo a comporta superior iluminada.
15:10
Now mice are smart, so this mouse solves the maze eventually,
385
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Hoxe os ratos son listos, así que este
sae do labirinto,
15:13
but he does a brute-force search.
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2000
pero busca por forza bruta.
Nada por tódalas vías ata que,
finalmente, chega á plataforma.
15:15
He's swimming down every avenue until he finally gets to the platform.
387
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3000
15:18
So he's not using vision to do it.
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E non está usando a visión para logralo.
15:20
These different mice are different mutations
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Estes ratos son mutacións distintas
que sintetizan distintos tipos de cegueira
que afectan aos humanos.
15:22
that recapitulate different kinds of blindness that affect humans.
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15:25
And so we're being careful in trying to look at these different models
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Por iso pomos moito coidado cando
observamos aos nosos modelos
de xeito que chegamos
a un enfoque xeneralizado.
15:28
so we come up with a generalized approach.
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2000
15:30
So how are we going to solve this?
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Así que, como imos resolver isto?
15:32
We're going to do exactly what we outlined in the previous slide.
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2000
Faremos o que esbozamos
na outra diapositiva.
15:34
We're going to take these blue light photosensors
395
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2000
Imos coller estes fotosensores de luz azul
15:36
and install them on a layer of cells
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2000
e ímolos instalar nunha capa de células
15:38
in the middle of the retina in the back of the eye
397
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3000
no medio da retina
na parte posterior do ollo
15:41
and convert them into a camera --
398
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2000
para convertela nunha cámara
como se instalásemos
15:43
just like installing solar cells all over those neurons
399
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2000
celas fotovoltaicas nas neuronas
15:45
to make them light sensitive.
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2000
para facelas sensibles á luz.
15:47
Light is converted to electricity on them.
401
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2000
Nelas a luz convértese en electricidade.
15:49
So this mouse was blind a couple weeks before this experiment
402
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3000
Así que este rato era cego un par
de semanas antes do experimento
15:52
and received one dose of this photosensitive molecule in a virus.
403
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3000
e recibiu unha dose desta molécula
fotosensible nun virus.
15:55
And now you can see, the animal can indeed avoid walls
404
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2000
E agora poden velo, o animal evita paredes
15:57
and go to this little platform
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2000
e vai a esa pequena plataforma
15:59
and make cognitive use of its eyes again.
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3000
e fai novamente
un uso cognitivo dos seus ollos.
16:02
And to point out the power of this:
407
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2000
E para destaca-lo poder que ten isto:
16:04
these animals are able to get to that platform
408
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2000
os animais poden chegar á plataforma
16:06
just as fast as animals that have seen their entire lives.
409
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2000
tan rápido coma os que viron toda a vida.
16:08
So this pre-clinical study, I think,
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Por iso penso que este estudo preclínico
16:10
bodes hope for the kinds of things
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é un bo presaxio para o tipo de cousas
16:12
we're hoping to do in the future.
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que esperamos facer no futuro.
16:14
To close, I want to point out that we're also exploring
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3000
Para acabar, quero sinalar
que tamén estamos a explorar
16:17
new business models for this new field of neurotechnology.
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2000
novos negocios neste campo
da neurotecnoloxía.
16:19
We're developing these tools,
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2000
Desenvolvemos estas ferramentas,
16:21
but we share them freely with hundreds of groups all over the world,
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2000
pero compartímolas con grupos
de todo o mundo
16:23
so people can study and try to treat different disorders.
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2000
de xeito que se estudan e tratan
moitos trastornos.
16:25
And our hope is that, by figuring out brain circuits
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E esperamos que, ao entender
os circuítos cerebrais
16:28
at a level of abstraction that lets us repair them and engineer them,
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3000
a un nivel de abstracción que nos
permita reparalos e deseñalos,
16:31
we can take some of these intractable disorders that I told you about earlier,
420
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3000
poidamos tomar algún dos trastornos
incurables dos que lles falei,
16:34
practically none of which are cured,
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2000
practicamente ningún deles ten cura,
16:36
and in the 21st century make them history.
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2000
e facer que no século XXI sexan historia.
16:38
Thank you.
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Grazas.
16:40
(Applause)
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(Aplausos)
16:53
Juan Enriquez: So some of the stuff is a little dense.
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3000
Juan Enriquez: Algunhas das cousas
son un pouco densas.
16:56
(Laughter)
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(Risas)
16:58
But the implications
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2000
Pero as consecuencias
17:00
of being able to control seizures or epilepsy
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3000
de poder controla-las convulsións
ou a epilepsia
17:03
with light instead of drugs,
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2000
con luz en vez de medicamentos,
17:05
and being able to target those specifically
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3000
e poder identificalos especificamente
17:08
is a first step.
431
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2000
é un primeiro paso.
17:10
The second thing that I think I heard you say
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Outra cosa que creo que dixeches
17:12
is you can now control the brain in two colors,
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3000
é que agora ti podes controla-lo cerebro
con dúas cores,
17:15
like an on/off switch.
434
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2000
como un interruptor de acender/apagar.
17:17
Ed Boyden: That's right.
435
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2000
Ed Boyden: Correcto.
17:19
JE: Which makes every impulse going through the brain a binary code.
436
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3000
JE: O que transforma cada impulso cerebral
nun código binario.
17:22
EB: Right, yeah.
437
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2000
EB: Correcto, si.
17:24
So with blue light, we can drive information, and it's in the form of a one.
438
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3000
Coa luz azul, podemos
conduci-la información en forma de un.
17:27
And by turning things off, it's more or less a zero.
439
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2000
E apagándoa sería, máis ou
menos, un cero.
17:29
So our hope is to eventually build brain coprocessors
440
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2000
Así esperamos, ao final, construír
17:31
that work with the brain
441
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2000
procesadores cerebrais que
funcionen co cerebro
17:33
so we can augment functions in people with disabilities.
442
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3000
para poder aumenta-las función das persoas
con discapacidade.
17:36
JE: And in theory, that means that,
443
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2000
JE: E en teoría, iso significa que,
17:38
as a mouse feels, smells,
444
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2000
o xeito en que un rato sente, ole,
17:40
hears, touches,
445
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2000
oe, toca,
17:42
you can model it out as a string of ones and zeros.
446
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3000
ti podes modelalo como unha cadea
de uns e ceros.
17:45
EB: Sure, yeah. We're hoping to use this as a way of testing
447
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2000
EB: Sí, claro. Esperamos usalo
para comprobar
17:47
what neural codes can drive certain behaviors
448
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2000
qué códigos neurais guían certos
comportamentos,
17:49
and certain thoughts and certain feelings,
449
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2000
e certos pensamentos e sentimentos,
17:51
and use that to understand more about the brain.
450
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3000
e para entender máis sobre o cerebro.
17:54
JE: Does that mean that some day you could download memories
451
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3000
JE: Significa iso que algún día
poderanse descargar recordos
17:57
and maybe upload them?
452
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2000
e quizais actualizalos?
EB: Ben, estamos empezando
a traballar a fondo niso.
17:59
EB: Well that's something we're starting to work on very hard.
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2000
18:01
We're now working on some work
454
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Agora estamos traballando
en revesti-lo cerebro
con elementos de gravación.
18:03
where we're trying to tile the brain with recording elements too.
455
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2000
18:05
So we can record information and then drive information back in --
456
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Así, poderemos gravar información
e despois recuperala
18:08
sort of computing what the brain needs
457
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2000
como calculando o que necesita o cerebro
18:10
in order to augment its information processing.
458
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2000
para aumenta-lo seu procesamento
de información.
18:12
JE: Well, that might change a couple things. Thank you. (EB: Thank you.)
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JE: Ben, iso podería cambiar algunhas
cousas. Grazas.
EB: Grazas.
18:15
(Applause)
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(Aplausos)

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ABOUT THE SPEAKER
Ed Boyden - Neuroengineer
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute.

Why you should listen

Ed Boyden leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain. His group applies these tools in a systematic way in order to reveal ground truth scientific understandings of biological systems, which in turn reveal radical new approaches for curing diseases and repairing disabilities. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision, and optogenetic tools, which enable the activation and silencing of neural activity with light (TED Talk: A light switch for neurons). Boyden also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.

Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013) and the NIH Director's Pioneer Award (2013). He was also named to the World Economic Forum Young Scientist list (2013) and the Technology Review World's "Top 35 Innovators under Age 35" list (2006). His group has hosted hundreds of visitors to learn how to use new biotechnologies and spun out several companies to bring inventions out of his lab and into the world. Boyden received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents and articles, and he has given over 300 invited talks on his group's work.

More profile about the speaker
Ed Boyden | Speaker | TED.com

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