Ed Boyden: A light switch for neurons

Translator: Luz Leirós Reviewer: Serv. de Norm. Lingüística U. de Santiago de Compostela

Pensen no seu día por un segundo.

Think about your day for a second.

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

Espertaron, sentiron o aire fresco na cara ao saír pola porta,

encountered new colleagues and had great discussions

atoparon novos colegas e tiveron bos debates,

e asombráronse ao atopar algo novo.

and felt in awe when you found something new.

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

Pero aposto a que hoxe non pensaron

en algo tan próximo a nós

something so close to home,

que non atrae a nosa atención moi a miúdo.

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

Que todas esas sensacións, sentimentos,

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

decisións e accións

son intermediadas por unha computadora na súa cabeza

are mediated by the computer in your head

called your brain.

á que chamamos cerebro.

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

E pode non parecer gran cousa dende fóra:

un quilo de carne de cor gris rosácea,

a couple pounds of pinkish-gray flesh,

amorphous.

amorfa,

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

pero os últimos cen anos de neurociencia

permitíronnos entrar no cerebro

and to see the intricacy of what lies within.

e ve-la complexidade do seu interior.

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

E dixéronnos que este cerebro

é un circuíto incriblemente complicado

made out of hundreds of billions of cells called neurons.

composto de centos de miles de millóns de células chamadas neuronas.

Now, unlike a human-designed computer,

Agora ben, ao contrario dunha computadora deseñada por humanos

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

con moitas menos pezas distintas

--sabemos como funcionan, posto que as deseñamos nos--

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

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

o cerebro está composto de miles de tipos diferentes de células,

quizais decenas de miles.

maybe tens of thousands.

De distintas formas, a partir de moléculas diversas,

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

e que proxectan e conectan cara a distintas rexións do cerebro.

they project and connect to different brain regions.

E tamén cambian nos diferentes estadios da enfermidade.

They also change in different ways in different disease states.

Let's make it concrete.

Sexamos máis concretos.

There's a class of cells,

Temos unha clase de células,

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

unha célula moi pequena, inhibidora, que silencia as súas veciñas.

É unha das células que se atrofiaría en trastornos como a esquizofrenia.

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

in disorders like schizophrenia.

It's called the basket cell.

É coñecida coma célula cesta;

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

E é un dos miles de tipos de células

acerca das cales estamos aprendendo.

that we're learning about.

New ones are being discovered every day.

Descóbrense novos tipos tódolos días.

As just a second example:

Só un segundo exemplo:

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

estas células piramidais, grandes células,

que abarcan unha parte importante do cerebro.

of the brain.

Son excitatorias.

They're excitatory.

E estas son algunhas das células

And these are some of the cells that might be overactive

que poderían estar hiperactivas en trastornos como a epilepsia.

in disorders such as epilepsy.

Every one of these cells is an incredible electrical device.

Cada unha destas células

é un dispositivo eléctrico incrible.

They receive inputs from thousands of upstream partners

Reciben sinais de miles de células da parte superior

and compute their own electrical outputs,

e calculan as súas propias respostas eléctricas

which then, if they pass a certain threshold,

que ao superar un determinado límite,

pasarán a miles de células da parte inferior.

will go to thousands of downstream partners.

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

E este proceso, que leva só un milisegundo máis ou menos,

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

sucede miles de veces por minuto

para cada unha das 100 mil millóns de células,

as long as you live and think and feel.

mentres vostedes viven,

e pensan e senten.

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

Así pois, como imos descifrar qué fai este circuíto?

Ideally, we could go through this circuit

O ideal sería ir a través del

e acender e apaga-los distintos tipos de células

and turn these different kinds of cell on and off

and see whether we could figure out

e ver se podemos esclarecer

which ones contribute to certain functions

cales contribúen a determinadas funcións

and which ones go wrong in certain pathologies.

e cales funcionan mal en certas patoloxías.

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

Se puideramos activalas poderíamos ver qué potencial liberan,

what they can initiate and sustain.

e qué poden iniciar e manter.

Se puideramos apagalas, entón

If we could turn them off,

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

poderíamos tentar ver para que son precisas.

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

E esa é unha historia que lles vou contar hoxe.

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

E, honestamente, por onde pasamos nos últimos 11 anos

na busca de maneiras

through an attempt to find ways

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

de acender e apagar circuítos e células

e rutas do cerebro,

on and off,

tanto para entende-la ciencia,

both to understand the science

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

como para facerlles fronte a algúns dos problemas

cos que todos batemos como humanos.

Now, before I tell you about the technology,

Pero antes de falarlles da tecnoloxía,

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

a mala nova é que unha parte significativa de nós nesta sala,

if we live long enough,

se vivímo-lo suficiente,

will encounter, perhaps, a brain disorder.

probablemente suframos un trastorno cerebral.

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

Xa mil millóns de persoas

tiveron algún tipo de trastorno cerebral

that incapacitates them.

que as incapacita,

The numbers don't do it justice, though.

e, porén, as cifras non lle fan xustiza.

These disorders -- schizophrenia, Alzheimer's,

Estes trastornos --a esquizofrenia, o alzheimer,

depression, addiction --

a depresión, a adicción--

they not only steal away our time to live,

non só nos rouban tempo de vida, cambian o noso ser.

they change who we are.

They take our identity and change our emotions

Quítannos a nosa identidade e cambian as nosas emocións

and change who we are as people.

e cambian o que somos como persoas.

Now, in the 20th century,

Agora ben, no século XX

there was some hope that was generated

xerouse algo de esperanza

through the development of pharmaceuticals for treating brain disorders.

grazas ao desenvolvemento de fármacos para trastornos cerebrais.

And while many drugs have been developed

E aínda que se desenvolveron moitas medicinas

that can alleviate symptoms of brain disorders,

que poden alivia-los síntomas deses trastornos,

practically none of them can be considered to be cured.

na práctica ningún deles pode considerarse curable.

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

En parte porque estamos inundando o cerebro con química.

we're bathing the brain in a chemical --

Este elaborado circuíto

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

composto de miles de tipos de células diferentes

está sendo bañado nunha substancia.

is being bathed in a substance.

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

Por iso, a maior parte das medicinas

pode presentar algún tipo de efecto secundario importante.

can present some kind of serious side effect too.

Now some people have gotten some solace from electrical stimulators

Agora, algunhas persoas recibiron algún consolo

de estimuladores eléctricos que se implantan no cerebro.

that are implanted in the brain,

for Parkinson's disease or cochlear implants.

E para o párkinson,

os implantes cocleares,

These have indeed been able to bring some kind of remedy

foron capaces

de fornecer algún alivio

to people with certain kinds of disorders.

a persoas con certos tipos de trastornos.

But electricity also will go in all directions --

Pero a electricidade tamén irá cara a todas partes

the path of least resistance --

pola ruta de menor resistencia,

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

e de aí, en parte, vén esta expresión.

and will also affect normal circuits,

E isto afectará aos circuítos normais pero tamén aos que queremos corrixir.

as well as the abnormal ones you want to fix.

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

Así que de novo, volvemos á idea

do control ultrapreciso.

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

Podemos dirixi-la información exactamente cara a onde queremos?

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

Cando comecei na neurociencia hai 11 anos

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

formárame como enxeñeiro eléctrico e como físico,

the first thing I thought about was,

e o primeiro que pensei foi:

if these neurons are electrical devices,

se as neuronas son dispositivos eléctricos

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

todo o que fai falla é atopa-lo modo

de manexar a distancia eses cambios eléctricos.

at a distance.

Se puideramos acende-la electricidade nunha célula,

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

pero non nas veciñas,

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

iso daríanos o que necesitamos para activar e apaga-las células,

para descubrir que fan e como contribúen

to figure out what they do

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

ás redes nas que están inseridas.

E tamén nos permitiría o control ultrapreciso

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

necesario para corrixi-los cálculos do circuíto

to fix the circuit computations that have gone awry.

que estiveran mal.

Now, how are we going to do that?

Agora, como imos facer iso?

Well, there are many molecules that exist in nature

Ben, na natureza haiche moitas moléculas

which are able to convert light into electricity.

capaces de converte-la luz en electricidade.

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

Imaxínenas como pequenas proteínas

que son como celas fotovoltaicas.

If we install these molecules in neurons somehow,

Se, dalgún xeito, podemos instalar estas moléculas nas neuronas

then these neurons would become electrically drivable with light,

entón estas neuronas poderían manipularse electricamente coa luz.

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

E as súas veciñas, que non teñen a molécula, non.

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

Cómprenos outro truco de maxia para que isto suceda:

the ability to get light into the brain.

a capacidade de meter luz no cerebro.

The brain doesn't feel pain.

E para logralo --o cerebro non sente dor-- pódese poñer

Taking advantage of all the effort

--aproveitando o esforzo

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

investido en Internet, comunicacións, etc--

you can put optical fibers connected to lasers

fibra óptica conectada a láseres

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

que pode usarse para activar, por exemplo en modelos animais,

en estudios preclínicos,

these neurons and see what they do.

estas neuronas e ver qué fan.

So how do we do this?

Entón, como o facemos?

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

Arredor de 2004,

en colaboración con Gerhard Nagel e Karl Deisseroth

this vision came to fruition.

esta visión fíxose realidade.

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

Hai unha alga que nada no mundo silvestre

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

e que ten que navegar cara á luz

para face-la fotosíntese de forma óptima.

And it senses light with a little eyespot,

E detecta a luz cun pequeno ocelo

which works not unlike how our eye works.

que funciona non moi distinto ca os nosos ollos.

In its membrane, or its boundary,

Na súa membrana, ou no seu bordo,

it contains little proteins

contén pequenas proteínas

que, de feito, poden converte-la luz en electricidade.

that indeed can convert light into electricity.

Estas moléculas denomínanse canalrodopsinas.

These molecules are called channelrhodopsins.

And each of these proteins acts just like that solar cell

E cada unha actúa como esa cela fotovoltaica da que falei.

that I told you about.

Ante a presenza de luz azul, abre un pequeno orificio

When blue light hits it,

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

que deixa pasar partículas cargadas ao ocelo.

o que lle permite ter un sinal eléctrico

that allows this eyespot to have an electrical signal,

just like a solar cell charging a battery.

como unha cela fotovoltaica que carga unha batería.

So what we need to do is take these molecules

Daquela,temos que toma-las moléculas

e poñelas dalgún xeito nas neuronas.

and somehow install them in neurons.

And because it's a protein,

E dado que é unha proteína,

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

está codificada no ADN deste organismo.

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

Así que o que temos que facer é toma-lo ADN,

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

colocalo nun vector de terapia xénica, coma un virus,

and put it into neurons.

E poñelo nas neuronas.

And this was a very productive time in gene therapy,

Resultou ser un momento moi produtivo en terapia xénica,

and lots of viruses were coming along,

e empezaron a aparecer moitos virus.

so this turned out to be fairly simple.

Así que resultou moi simple de facer.

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

E unha mañanciña do verán de 2004

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

tentámolo e funcionou á primeira.

You take this DNA and put it into the neuron.

Tómase este ADN e colócase nunha neurona.

The neuron uses its natural protein-making machinery

A neurona usa o seu mecanismo natural de elaboración de proteínas

to fabricate these little light-sensitive proteins

para facer pequenas proteínas fotosensibles

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

e colocalas por toda a célula,

como paneis solares nun tellado,

And the next thing you know,

e o seguinte que sabemos

you have a neuron which can be activated with light.

é que temos unha neurona activable por luz.

So this is very powerful.

E isto é moi valioso.

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

Un dos trucos que tes que facer

é atopar como leva-los xenes ás células que queres

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

E non a tódalas súas veciñas.

E pode facerse; pódese axusta-lo virus

And you can do that;

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

para que acade unhas células e non outras.

And there's other genetic tricks you can play

E hai outros trucos xenéticos aos que recorrer

in order to get light-activated cells.

co fin de obter células fotoactivadas.

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

Este campo coñécese como optoxenética.

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

E, como exemplo de cousas que se poden facer,

you can take a complex network,

podes tomar unha rede complexa,

use one of these viruses to deliver the gene

usar un destes virus para entrega-lo xene

just to one kind of cell in this dense network.

a un só tipo de célula nesta densa rede.

And then when you shine light on the entire network,

E despois cando a luz ilumina toda a rede

just that cell type will be activated.

só se activará ese tipo de célula.

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

Por exemplo, pensemos nesa célula cesta que lles mencionei antes,

a que se atrofia na esquizofrenia

the one that's atrophied in schizophrenia

e que é inhibitoria.

and the one that is inhibitory.

Se podemos levar ese xene a esas células

If we can deliver that gene to these cells --

e que non se vexan alteradas pola expresión dese xene, por suposto,

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

then flash blue light over the entire brain network,

e despois iluminamos de azul toda a rede cerebral

just these cells are going to be driven.

só se verán afectadas esas células.

E cando apagamos a luz as células volven á normalidade,

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

there don't seem to be adverse events.

así que iso non parece afectalas .

Not only can you study what these cells do,

Non só se usa para estuda-lo funcionamento celular,

what their power is in computing in the brain,

o seu poder de cómputo no cerebro,

senón tamén para tratar de descubrir

you can also use this to try to figure out

se poderiamos animar a actividade desas células

if we could jazz up the activity of these cells

se realmente están atrofiadas.

if indeed, they're atrophied.

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

Agora quero contarlles un par de historias breves

both at the scientific clinical and preclinical levels.

acerca do uso que facemos disto,

a nivel científico, clínico e preclínico.

One of the questions that we've confronted is:

Unha das preguntas a que nos enfrontamos é

What signals in the brain mediate the sensation of reward?

cales son os sinais cerebrais implicados na sensación de recompensa?

Because if you could find those,

Porque se puideramos atopalos

serían os sinais que poderían guia-la aprendizaxe.

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

O cerebro repetirá o que o gratifica.

the brain will do more of what got that reward.

E ademais, estes sinais funcionan mal nos trastornos adictivos.

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

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

Así, se descubrísemos esas células

quizais poderiamos atopar novas dianas

para as que deseñar ou probar medicamentos,

for which drugs can be designed or screened against

ou quizais lugares nos que colocar eléctrodos

or maybe places where electrodes could be put in

for people who have severe disability.

para persoas con discapacidades moi graves.

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

Para isto, ocorréusenos un paradigma moi simple

in collaboration with the Fiorillo group,

en colaboración co grupo Fiorella,

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

nun lado desta pequena caixa,

se o animal vai alí, recibe un pulso de luz

it gets a pulse of light.

que fará fotosensibles varias células cerebrais.

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

Así, se estas células participan na recompensa,

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

o animal debería ir alí cada vez máis.

And that's what happens.

Iso é o que sucede.

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

O animal vai ir mete-lo nariz ao lado dereito

e cada vez que o fai recibe un flash azul.

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

E farao centos e centos de veces.

He'll do that hundreds of times.

Son as neuronas dopamina,

These are the dopamine neurons,

que como saberán, participan dos centros cerebrais do pracer.

in some of the pleasure centers in the brain.

Demostramos que activalas brevemente

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

é suficiente para guia-la aprendizaxe.

Now we can generalize the idea.

Podemos xeneraliza-la idea.

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

En lugar de un só punto no cerebro

podemos idear dispositivos para todo o cerebro,

that can deliver light into three-dimensional patterns --

que leven a luz en patróns tridimensionais

arrays of optical fibers,

--matrices de fibra óptica,

cunha minifonte luminosa independente.

each coupled to its own independent miniature light source.

Then we can try to do things in vivo

E podemos tratar de facer en vivo

o que, ata o momento, se fixo só nunha placa,

that have only been done to date in a dish,

like high-throughput screening throughout the entire brain

como a visualización completa do cerebro

para sinais que fan que sucedan certas cousas.

for the signals that can cause certain things to happen

Ou poderían ser bos obxectivos clínicos

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

para o tratamento de trastornos cerebrais.

One story I want to tell you about is:

E outra historia que quero contarlles

é como atopamos dianas para trata-lo estrés postraumático,

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

unha forma de ansiedade e medo descontrolados.

a form of uncontrolled anxiety and fear?

E unha das cousas que fixemos

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

foi adopta-lo modelo máis clásico do medo.

This goes back to the Pavlovian days.

Remóntase aos días de Pavlov.

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

Denomínase medo condicionado pavloviano,

e nel un ton remata cunha breve descarga.

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

A descarga non doe, pero molesta un pouco.

E co tempo --un rato,

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

un bo modelo animal, usado a miúdo en experimentos,

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

aprende a temerlle ao ton.

the animal learns to fear the tone.

O animal reaccionará paralizándose,

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

coma un cervo diante dos faros.

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

Agora, a pregunta é, que dianas podemos atopar no cerebro

that allow us to overcome this fear?

que nos permitan superar ese temor?

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

Para iso reproducimos o ton novamente

despois de que se asocie co medo.

But we activate different targets in the brain,

Pero activamos novas dianas no cerebro,

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

usando esa matriz de fibra óptica que lles mostrei antes

para tratar de desvelar qué dianas

in order to try and figure out

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

poden facer que o cerebro supere esa memoria do medo.

This brief video shows you one of these targets

Este breve vídeo

mostra unha das dianas con que traballamos.

that we're working on now.

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

Unha área do córtex prefrontal, unha rexión

na que pode usarse a cognición para superar estados aversivos.

to try to overcome aversive emotional states.

Cando o animal oe un ton, aparece un flash.

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

Non o oen, pero ven que o rato se paraliza.

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

O ton adoitaba representar malas noticias.

the tone used to mean bad news.

Hai un reloxo na esquina inferior esquerda

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

para que poidan ver que o animal queda así uns 2 minutos.

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

E agora, o seguinte vídeo,

This next clip is just eight minutes later.

de só 8 minutos despois.

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

Vaise reproduci-lo ton, e a luz dispárase outra vez.

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

Ben, aí vai. Xusto agora.

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

E agora poden ver, en só 10 minutos de experimento,

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

que preparamos o cerebro, fotoactivando esta zona,

para supera-la expresión

to overcome the expression of this fear memory.

desta memoria do medo.

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

Durante os últimos dous anos, volvemos atrás na árbore da vida

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

porque queriamos atopar modos de apaga-los circuítos cerebrais.

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

Se puideramos facelo sería algo moi poderoso.

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

Se podes suprimir células durante uns milisegundos ou segundos,

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

podes darte de conta da súa relevancia

nos circuítos en que están inseridas.

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

E estudamos toda a árbore da vida,

seres de tódolos reinos salvo o animal, que é levemente distinto.

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

E atopamos moléculas chamadas halorrodopsinas ou arqueorrodopsinas,

We found molecules called halorhodopsins or archaerhodopsins,

que responden á luz verde e amarela.

that respond to green and yellow light.

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

E que fan o oposto da molécula anterior,

a do activador de luz azul, a canalrodopsina.

with the blue light activator, channelrhodopsin.

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

Vexamos un exemplo de cara a onde pensamos que vai isto.

Consider, for example, a condition like epilepsy,

Consideren, por exemplo, unha doenza como a epilepsia,

where the brain is overactive.

na que o cerebro é hiperactivo.

Now, if drugs fail in epileptic treatment,

Se falla a medicación no tratamento da epilepsia,

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

pode eliminarse parte do cerebro.

Pero isto é irreversible e ten efectos secundarios.

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

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

Que pasaría se puideramos apaga-lo cerebro por un breve instante

ata que o ataque esvaecera

until the seizure dies away,

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

e facer que o cerebro volvera ao seu estado inicial?

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

Algo así coma un sistema dinámico dirixido cara a un estado estable.

This animation tries to explain this concept

Esta animación tenta explicar este concepto

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

onde creamos células sensibles a desactivarse coa luz,

e enfocámo-la luz sobre elas,

and we beam light in,

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

e só durante o tempo que dura a convulsión

esperamos ser capaces de apagalas.

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

Non temos datos para amosar neste campo,

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

pero estamos moi ilusionados.

but we're very excited about this.

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

Agora quero rematar cunha historia,

que nos parece outra posibilidade

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

e que, se acadamos un control ultrapreciso,

talvez permita usar estas moléculas no propio cerebro

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

para facer un novo tipo de prótese óptica.

an optical prosthetic.

Xa dixen que os estimuladores eléctricos son comúns hoxe.

I already told you that electrical stimulators are not uncommon.

Seventy-five thousand people

75 mil persoas teñen estimuladores cerebrais para o párkinson.

have Parkinson's deep-brain stimulators implanted,

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

Talvez 100 mil teñan implantes cocleares,

que lles permiten oír.

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

Outra cosa é que temos que meter eses xenes nas células.

A new hope in gene therapy has been developed,

E xurdiu unha nova esperanza en terapia xénica

because viruses like the adeno-associated virus --

grazas a virus como o virus adenoasociado,

que probablemente a maioría de vostedes terá

which probably most of us around this room have;

it doesn't have any symptoms --

sen presentar síntomas,

e que se empregou en centos de pacientes

have been used in hundreds of patients

to deliver genes into the brain or the body.

para repartir xenes no cerebro e no corpo.

And so far, there have not been serious adverse events

E, ata o de agora, non houbo efectos adversos graves

asociados co virus.

associated with the virus.

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

Tamén adoitamos ignorar outro gran problema: as propias proteínas,

which come from algae, bacteria and funguses

procedentes de algas, bacterias e fungos,

and all over the tree of life.

e toda a árbore da vida.

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

A maioría non temos fungos nin algas no cerebro,

así que, que fará o cerebro se llas inserimos?

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

Tolerarano as células? E o sistema inmunolóxico?

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

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

Estamos comezando, non se probou en humanos

pero estamos a traballar en varios estudos

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

tratando de examinalo,

e, ata o de agora, non atopamos reaccións graves

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

cara a estas moléculas

to these molecules

or to the illumination of the brain with light.

ou cara á iluminación do cerebro con luz.

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

Sinceramente, estamos comezando pero estamos entusiasmados.

I wanted to close with one story,

Quero rematar cunha historia,

which we think could potentially be a clinical application.

que, cremos, podería

ser unha aplicación clínica.

Now, there are many forms of blindness

Hoxe en día hai moitas formas de cegueira

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

nas que os fotorreceptores,

os sensores de luz que están no fondo do ollo, non funcionan.

are gone.

And the retina is a complex structure.

E a retina é unha estrutura complexa.

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

Agora ampliémolo, para velo mellor.

The photoreceptor cells are shown here at the top.

As células fotorreceptoras amósanse aquí arriba

The signals that are detected by the photoreceptors are transformed

e os sinais detectados por elas

son transformados por varios cálculos

via various computations

ata que, ao final, a capa de células ganglionares de abaixo

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

transmite a información ao cerebro,

relay the information to the brain,

onde vemos iso como percepción.

where we see that as perception.

In many forms of blindness, like retinitis pigmentosa

En moitas formas de cegueira, como a retinite pigmentosa,

or macular degeneration,

ou a dexeneración macular,

the photoreceptor cells have atrophied or been destroyed.

as células fotorreceptoras atrofiáronse ou destruíronse.

Now, how could you repair this?

Como arranxar isto?

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

Nin sequera está claro que un fármaco poida facelo

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

porque non ten nada ao que ligarse.

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

Por outra banda, a luz aínda pode entrar no ollo.

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

O ollo aínda é transparente e permite o paso da luz.

Así que, e se collemos as canalrodopsinas e outras moléculas

So what if we could take these channelrhodopsins and other molecules

e as poñemos nalgunha destoutras células libres

and install them on some of these other spared cells

e as convertemos en pequenas cámaras?

and convert them into little cameras?

E, xa que hai moitas destas células no ollo,

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

potencialmente, poderían ser cámaras de moi alta definición.

potentially, they could be very high-resolution cameras.

This is some work that we're doing,

Velaquí o noso traballo en curso.

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

Está dirixido por un dos nosos colaboradores,

Alan Horsager na USC,

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

e procuramos que sexa comercializado por unha empresa nova,

Eos Neuroscience, financiada polo NIH.

which is funded by the NIH.

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

Aquí vemos un rato tentando saír dun labirinto.

É un labirinto de 6 brazos con auga

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

para que o rato se mova e non quede sentado.

O obxectivo deste labirinto, por suposto,

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

é saír da auga e subir a unha plataforma

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

baixo a comporta superior iluminada.

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

Hoxe os ratos son listos, así que este sae do labirinto,

but he does a brute-force search.

pero busca por forza bruta.

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

Nada por tódalas vías ata que, finalmente, chega á plataforma.

He's not using vision to do it.

E non está usando a visión para logralo.

These different mice are different mutations

Estes ratos son mutacións distintas

que sintetizan distintos tipos de cegueira que afectan aos humanos.

that recapitulate different kinds of blindness that affect humans.

Por iso pomos moito coidado cando observamos aos nosos modelos

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

de xeito que chegamos a un enfoque xeneralizado.

so we come up with a generalized approach.

So how can we solve this?

Así que, como imos resolver isto?

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

Faremos o que esbozamos na outra diapositiva.

We'll take these blue light photo sensors

Imos coller estes fotosensores de luz azul

and install them onto a layer of cells

e ímolos instalar nunha capa de células

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

no medio da retina na parte posterior do ollo

and convert them into a camera --

para convertela nunha cámara como se instalásemos

just like installing solar cells all over those neurons

celas fotovoltaicas nas neuronas

para facelas sensibles á luz.

to make them light-sensitive.

Light is converted to electricity on them.

Nelas a luz convértese en electricidade.

So this mouse was blind a couple weeks before this experiment

Así que este rato era cego un par de semanas antes do experimento

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

e recibiu unha dose desta molécula fotosensible nun virus.

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

E agora poden velo, o animal evita paredes

and go to this little platform

e vai a esa pequena plataforma

e fai novamente un uso cognitivo dos seus ollos.

and make cognitive use of its eyes again.

And to point out the power of this:

E para destaca-lo poder que ten isto:

os animais poden chegar á plataforma

these animals can get to that platform

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

tan rápido coma os que viron toda a vida.

Por iso penso que este estudo preclínico

So this preclinical study, I think, bodes hope

é un bo presaxio para o tipo de cousas

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

que esperamos facer no futuro.

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

Para acabar, quero sinalar que tamén estamos a explorar

novos negocios neste campo da neurotecnoloxía.

We're developing tools and sharing them freely

Desenvolvemos estas ferramentas,

pero compartímolas con grupos de todo o mundo

with hundreds of groups all over the world

for them to study and try to treat different disorders.

de xeito que se estudan e tratan moitos trastornos.

Our hope is that by figuring out brain circuits

E esperamos que, ao entender os circuítos cerebrais

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

a un nivel de abstracción que nos permita reparalos e deseñalos,

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

poidamos tomar algún dos trastornos incurables dos que lles falei,

practically none of which are cured,

practicamente ningún deles ten cura,

and in the 21st century, make them history.

e facer que no século XXI sexan historia.

Thank you.

Grazas.

(Applause)

(Aplausos)

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

Juan Enriquez: Algunhas das cousas son un pouco densas.

(Laughter)

(Risas)

But the implications of being able to control seizures or epilepsy

Pero as consecuencias

de poder controla-las convulsións ou a epilepsia

with light instead of drugs

con luz en vez de medicamentos,

and being able to target those specifically

e poder identificalos especificamente

is a first step.

é un primeiro paso.

The second thing that I think I heard you say

Outra cosa que creo que dixeches

is you can now control the brain in two colors,

é que agora ti podes controla-lo cerebro con dúas cores,

like an on-off switch.

como un interruptor de acender/apagar.

Ed Boyden: That's right.

Ed Boyden: Correcto.

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

JE: O que transforma cada impulso cerebral nun código binario.

EB: Right.

EB: Correcto, si.

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

Coa luz azul, podemos conduci-la información en forma de un.

E apagándoa sería, máis ou menos, un cero.

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

Así esperamos, ao final, construír

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

procesadores cerebrais que funcionen co cerebro

para poder aumenta-las función das persoas con discapacidade.

so we can augment functions in people with disabilities.

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

JE: E en teoría, iso significa que,

o xeito en que un rato sente, ole,

oe, toca,

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

ti podes modelalo como unha cadea de uns e ceros.

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

EB: Sí, claro. Esperamos usalo para comprobar

what neural codes can drive certain behaviors

qué códigos neurais guían certos comportamentos,

and certain thoughts and certain feelings

e certos pensamentos e sentimentos,

and use that to understand more about the brain.

e para entender máis sobre o cerebro.

JE: Does that mean that someday you could download memories

JE: Significa iso que algún día poderanse descargar recordos

and maybe upload them?

e quizais actualizalos?

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

EB: Ben, estamos empezando a traballar a fondo niso.

Agora estamos traballando

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

en revesti-lo cerebro con elementos de gravación.

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

Así, poderemos gravar información e despois recuperala

sort of computing what the brain needs

como calculando o que necesita o cerebro

in order to augment its information processing.

para aumenta-lo seu procesamento de información.

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

JE: Ben, iso podería cambiar algunhas cousas. Grazas.

EB: Thank you.

EB: Grazas.

(Applause)

(Aplausos)