Ed Boyden: A light switch for neurons

Translator: BAW Beograd Reviewer: Tilen Pigac - EFZG

Razislite o svom danu jedan trenutak.

Think about your day for a second.

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

Probudili ste se. Osetili ste svež vazduh na licu izlazeći iz kuće,

encountered new colleagues and had great discussions

sreli ste nove kolege i imali sjajne razgovore,

i osetili strahopoštovanje kada ste otkrili nešto novo.

and felt in awe when you found something new.

Ali kladim se da postoji stvar na koju danas niste pomislili --

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

nešto svima tako blisko

something so close to home,

da verovatno o tome ne mislite uopšte.

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

A mislim na to da u svemu što zapazite, osetite,

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

odlučite i uradite

posreduje kompjuter u vašoj glavi

are mediated by the computer in your head

koji zovemo mozak.

called your brain.

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

Znam da mozak ne izgleda bog zna kako spolja --

par kilograma ružičasto-sive mase,

a couple pounds of pinkish-gray flesh,

amorfne --

amorphous.

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

ali poslednjih stotinjak godina neuronauke

su nam omogućile da "zumiramo" mozak

and to see the intricacy of what lies within.

i vidimo komplikovanost onoga što se nalazi unutra.

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

Oni nam govore da je mozak

neverovatno komplikovano ispovezivan

made out of hundreds of billions of cells called neurons.

sačinjen od stotina milijardi ćelija zvanih neuroni.

Now, unlike a human-designed computer,

Nasuprot kompjuteru koji su napravili ljudi,

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

koji čini relativno mali broj različitih delova --

za njih znamo kako rade jer smo ih mi, ljudi, dizajnirali --

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

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

mozak se sastoji od hiljada različitih vrsta ćelija,

možda desetina hiljada.

maybe tens of thousands.

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

Te ćelije su različitih oblika; čine ih različiti molekuli;

i one projektuju i povezuju se sa različitim regijama mozga.

they project and connect to different brain regions.

One se i menjaju na različite načine u različitim stadijumima bolesti.

They also change in different ways in different disease states.

Da konkretizujem.

Let's make it concrete.

There's a class of cells,

Postoji klasa ćelija,

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

prilično mala ćelija, inhibitorna ćelija, koja umiruje susedne.

Čini se da te ćelije atrofiraju u stanjima kao što je šizofrenija.

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

in disorders like schizophrenia.

It's called the basket cell.

Zovu je korpasta ćelija.

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

Ta ćelija je jedna od hiljada vrsta ćelija

o kojima učimo.

that we're learning about.

New ones are being discovered every day.

Nove otkrivaju svakoga dana.

Evo drugog primera:

As just a second example:

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

ove piramidalne ćelije, velike ćelije,

one se mogu prostirati značajnim delom mozga.

of the brain.

One su pobuđujuće.

They're excitatory.

I to su samo neke od ćelija

And these are some of the cells that might be overactive

koje bi mogle biti previše aktivne u poremećajima kao što je epilepsija.

in disorders such as epilepsy.

Svaka od ovih ćelija

Every one of these cells is an incredible electrical device.

je neverovatna električna naprava.

They receive inputs from thousands of upstream partners

One primaju podatke od hiljada prethodećih partnera

i proračunavaju njihov sopstveni električni izlaz,

and compute their own electrical outputs,

which then, if they pass a certain threshold,

koji onda, ako pređu određeni prag,

nastavlja ka hiljadama narednih partnera.

will go to thousands of downstream partners.

Taj proces, koji traje praktično samo milisekundu,

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

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

odvija se hiljadama puta u minuti

u svakoj od vaših 100 milijardi ćelija,

as long as you live and think and feel.

dok ste živi

i mislite i osećate.

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

I kako ćete da odgonetnete šta to kolo radi?

U idealnoj varijanti, mogli bi da prođemo tim kolom

Ideally, we could go through this circuit

i tom prilikom da te raznorazne ćelije aktiviramo i deaktiviramo

and turn these different kinds of cell on and off

and see whether we could figure out

i vidimo da li tako možemo da zaključimo

which ones contribute to certain functions

koje učestvuju u određenim funkcijama

and which ones go wrong in certain pathologies.

a koje se kvare usled nekih patologija.

Ako bismo mogli da aktiviramo ćelije, mogli bi videti energiju koju one oslobađaju,

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

šta mogu da iniciraju i podrže.

what they can initiate and sustain.

Ako bismo mogli da ih isključimo,

If we could turn them off,

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

onda bi mogli da pokušamo da odgonetnemo za šta su neophodne.

E to je priča koju ću vam danas ispričati.

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

Iskreno, kuda smo prošli u prethodnih 11 godina,

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

pokušavajući da nađemo načine

through an attempt to find ways

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

da kola i ćelije i delove i putanje u mozgu

aktiviramo i deaktiviramo

on and off,

i da bi razumeli nauku,

both to understand the science

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

ali i da bi se suočili sa nekim pitanjima

koja se tiču svih nas, ljudskih bića.

Now, before I tell you about the technology,

Sada, pre priče o tehnologiji,

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

loša vest je da će značajan broj nas u ovoj prostoriji,

ako poživimo dovoljno dugo,

if we live long enough,

will encounter, perhaps, a brain disorder.

verovatno, doživeti neki moždani poremećaj.

Već sada, milijarda ljudi

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

pati od neke vrste moždanog poremećaja

koja ih onesposobljava.

that incapacitates them.

The numbers don't do it justice, though.

A brojevi nam nisu naklonjeni.

These disorders -- schizophrenia, Alzheimer's,

Ti poremećaji -- šizofrenija, Alchajmer,

depresija, zavisnosti --

depression, addiction --

they not only steal away our time to live,

ne samo da nam skraćuju životni vek, oni nas menjaju;

they change who we are.

They take our identity and change our emotions

oni nam oduzimaju identitet i menjaju naša osećanja --

and change who we are as people.

i menjaju nas kao osobe.

Now, in the 20th century,

Sada, u 20. veku,

postojala je nada koju je generisao

there was some hope that was generated

through the development of pharmaceuticals for treating brain disorders.

razvoj farmaceutskih proizvoda za tretiranje moždanih poremećaja.

Dok su razvijani mnogi lekovi

And while many drugs have been developed

that can alleviate symptoms of brain disorders,

koji ublažavaju simptome moždanih poremećaja,

praktično nijedan od njih nije moga biti izlečen.

practically none of them can be considered to be cured.

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

Deo razloga je što preplavljujemo mozak hemikalijama.

we're bathing the brain in a chemical --

Ovo složeno kolo

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

sačinjeno od hiljada različitih vrsta ćelija

počinje da biva preplavljeno supstancama.

is being bathed in a substance.

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

Možda je to razlog zašto većina lekova, ali ne svi, koji su na tržištu

ima ozbiljne neželjene efekte.

can present some kind of serious side effect too.

Neki ljudi nalaze utehu

Now some people have gotten some solace from electrical stimulators

od električnih stimulatora koji su im ugrađeni u mozak.

that are implanted in the brain,

for Parkinson's disease or cochlear implants.

Ili u slučaju Parkinsonove bolesti,

kohlearni implanti,

These have indeed been able to bring some kind of remedy

koji su zaista uspeli

da donesu neku vrstu poboljšanja

to people with certain kinds of disorders.

ljudima sa određenim vrstama poremećaja.

But electricity also will go in all directions --

Ali elektricitet ide u svim pravcima --

the path of least resistance --

putem manjeg otpora,

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

što je, delom, i poreklo fraze.

and will also affect normal circuits,

A uticaće i na normalna kola baš kao i na abnormalna koja želite da popravite.

as well as the abnormal ones you want to fix.

I tako smo se vratili ideji

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

ultra precizne kontrole.

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

Možemo li poslati informaciju precizno tamo gde želimo da ona ode?

I tako, kada sam ja počeo da se bavim neuronaukom pre 11 godina,

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

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

posedovao sam znanja električnog inženjera i fizičara,

the first thing I thought about was,

a prva stvar koju su me naučili je bila

if these neurons are electrical devices,

da ako su neuroni električni sklopovi,

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

sve što treba da uradimo je da nađemo način

da izvedemo električne promene sa daljine.

at a distance.

Ako bi mogli da izazovemo elekticitet u jednoj ćeliji,

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

ali ne i u susednoj,

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

to bi nam dalo alat koji nam treba da aktiviramo i deaktiviramo te različite ćelije,

da otkrijemo šta one rade i kako doprinose

to figure out what they do

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

mreži u koju su smeštene.

To bi nam omogućilo i da imamo ultra precizne kontrole koje nam trebaju

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

da bi mogli da popravimo rezultate kola

to fix the circuit computations that have gone awry.

koja su zastranila.

Now, how are we going to do that?

Kako ćemo to da uradimo?

Well, there are many molecules that exist in nature

Pa, u prirodi postoje mnogi molekuli

koji su sposobni da pretvore svetlost u elektricitet.

which are able to convert light into electricity.

Možete o njima misliti kao o malim proteinima

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

koji su kao solarne ćelije.

If we install these molecules in neurons somehow,

Ako bi nekako mogli da instaliramo te molekule u neurone

then these neurons would become electrically drivable with light,

onda bi ti neuroni postali elektro-upravljivi svetlom.

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

A njihovi susedi, koji nemaju dodate molekule, ne bi bili.

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

Postoji još jedan magični trik koji vam treba da bi se sve ovo desilo

a to je načičn da uvedete svetlost u mozak.

the ability to get light into the brain.

The brain doesn't feel pain.

Da bi to uradili -- mozak ne oseća bol -- možete ugraditi --

Taking advantage of all the effort

zahvaljujući svemu što je uloženo

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

u razvoj internet i komunikacije i slično --

you can put optical fibers connected to lasers

optička vlakna prikopčana na lasere

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

koja možete koristiti za aktiviranje, na primer u životinjskim modelima,

u predkliničkim studijama,

these neurons and see what they do.

ovih neurona i tako videti šta rade.

Pa kako ćemo to da izvedemo?

So how do we do this?

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

U 2004. godini,

u saradnji sa Gerhardom Najdželom i Karlom Deiserotom,

this vision came to fruition.

ova vizija je dala plodove.

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

Postoji alga koja obitava u divljini,

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

i ona se kreće prema svetlu

da bi optimalno obavljala fotosintezu.

And it senses light with a little eyespot,

Ona oseća svetlost malom tačkom-okom,

which works not unlike how our eye works.

koja funkcioniše ne bitno različito od našeg oka.

In its membrane, or its boundary,

U membrani, ili na njenoj granici,

it contains little proteins

sadrži male proteine

koji zaista pretvaraju svetlost u elektricitet.

that indeed can convert light into electricity.

Ti molekuli se zovu channelrhodopsin-i

These molecules are called channelrhodopsins.

And each of these proteins acts just like that solar cell

I svaki od tih proteina deluje kao solarna ćelija o kojoj sam vam pričao.

that I told you about.

Kada je pogodi plavo svetlo, otvori se mala rupa

When blue light hits it,

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

i čestica sa nabojem uđe u tačku-oko.

Time tačka-oko dobija električni impuls

that allows this eyespot to have an electrical signal,

baš kao solarna ćelija koja puni bateriju.

just like a solar cell charging a battery.

So what we need to do is take these molecules

Znači, ono što treba da uradimo je da uzmemo te molekule

i nekako ih instaliramo u neurone.

and somehow install them in neurons.

And because it's a protein,

A pošto su to proteini,

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

kodirani su za DNK tih organizama.

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

Sve što treba da uradimo je da uzmemo tu DNK

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

ubacimo je u okviru genske terapije, kao virus,

and put it into neurons.

i ugradimo je u neuron.

And this was a very productive time in gene therapy,

Ispostavilo se da je ovo veoma produktivno vreme u smislu genske terapije,

and lots of viruses were coming along,

i mnogi virusi su se pojavljivali.

so this turned out to be fairly simple.

Tako je ovo postalo lako izvodivo.

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

Ranim jutrom jednog dana u septembru 2004.

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

pokušali smo i proradilo je iz prve.

Uzmete ovu DNK i stavite je u neuron.

You take this DNA and put it into the neuron.

The neuron uses its natural protein-making machinery

Neuroni su koristili prirodan proces za pravljenje proteina

to fabricate these little light-sensitive proteins

da bi prizveli ove male fotoosetljive proteine

i instalirali ih svuda po ćeliji,

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

kao što se postavljaju solarni paneli na krov.

And the next thing you know,

I tek tako,

you have a neuron which can be activated with light.

imate neuron koji može da se aktivira pomoću svetla.

To je tako moćno.

So this is very powerful.

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

Jedna od stvari koje treba da uradite

je da odgonetnete kako da isporučite te gene u ćelije koje ste odredili

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

a ne u sve ćelije u okolini.

I to može da se uradi; moguće je "oblikovati" viruse

And you can do that;

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

tako da pogode samo određene ćelije a ne neke druge.

A postoje i drugi genetičarski trikovi koje možete primeniti

And there's other genetic tricks you can play

da bi dobili ćelije koje se aktiviraju svetlom.

in order to get light-activated cells.

Ova oblast je sada poznata kao optogenetika.

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

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

Evo jedan primer onoga što možete da uradite,

možete uzeti kompleksnu mrežu i

you can take a complex network,

use one of these viruses to deliver the gene

upotrebiti neki od virusa da isporučite gen

samo jednoj vrsti ćelija u toj gustoj mreži.

just to one kind of cell in this dense network.

And then when you shine light on the entire network,

Kada obasjate svetlom celu mrežu

just that cell type will be activated.

aktiviraće se samo odabrana vrsta ćelija.

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

Na primer, hajde da vidimo one korpaste ćelije o kojima sam ranije pričao --

one koje atrofiraju u šizofreniji

the one that's atrophied in schizophrenia

koje su inhibitorne.

and the one that is inhibitory.

Ako možemo da isporučimo odabrane gene tim ćelijama --

If we can deliver that gene to these cells --

naravno, to ih neće, u genetskom smislu, promeniti --

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

i ako onda obasjamo plavom svetlošću kompletnu moždanu mrežu,

then flash blue light over the entire brain network,

just these cells are going to be driven.

samo će se odabrane ćelije pokrenuti.

Kada ugasimo svetlo, te ćelije će se vratiti u normalu

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

tako da nisu trajno izmenjene.

there don't seem to be adverse events.

Not only can you study what these cells do,

Ne samo da ovo možete da koristite da bi studirali šta ove ćelije rade,

what their power is in computing in the brain,

koji je njihov značaj u proračunima mozga,

nego možete koristiti ovo da bi pokušali da odgonetnete --

you can also use this to try to figure out

možda bi mogli da oživimo aktivnosti ovih ćelija,

if we could jazz up the activity of these cells

ako one zaista atrofiraju.

if indeed, they're atrophied.

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

Sada bih želeo da vam ispričam nekoliko kratkih priča

o tome kako koristimo ovo,

both at the scientific clinical and preclinical levels.

na naučnom, kliničkom i predkliničkom nivou.

One of the questions that we've confronted is:

Jedno od pitanja sa kojima smo se susreli

What signals in the brain mediate the sensation of reward?

je koji signali u mozgu posreduju osećaju nagrade?

Because if you could find those,

Jer ako možemo da pronađemo njih,

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

to bi bili neki od signala koji bi mogli da podstiču učenje.

Mozak bi radio više onoga što se nagrađuje.

the brain will do more of what got that reward.

Ujedno, to su signali koji oslabe pri poremećajima kao što je zavisnost.

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

Ako bi mogli da odgonetnemo koje su to ćelije,

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

možda bi mogli da nađemo nove ciljeve

za koje bi mogli da napravimo lekove ili koje bi mogli da izolujemo,

for which drugs can be designed or screened against

ili možda mesta u koja bi mogli da uvedemo elektrode

or maybe places where electrodes could be put in

ljudima koji pate od ozbiljnih invaliditeta.

for people who have severe disability.

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

Da bi to uradili, smislili smo veoma jednostavan primer

u saradnji sa Fiorela grupom,

in collaboration with the Fiorillo group,

u kome na jednoj strani ove male kutije,

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

ako životinja prođe tuda, životinja dobije bljesak svetla

it gets a pulse of light.

da bi učinila druge ćelije mozga osetljive na svetlo.

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

Ako te ćelije posreduju pri nagradi,

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

životinja će sve više i više ići tuda.

I to se i desilo.

And that's what happens.

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

Ova životinja će ići ka desnoj strani i promoliće nos tamo,

i dobiti bljesak plavog svetla svaki put kada to učini.

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

I ona će to učiniti stotine i stotine puta.

He'll do that hundreds of times.

Ovo su neuroni dopamina,

These are the dopamine neurons,

o kojima su neki od vas možda čuli, u nekim od centara za zadovoljstvno u mozgu.

in some of the pleasure centers in the brain.

Pokazali smo da je njihova kratka aktivacija

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

dovoljna, zaista, da bi podstakla učenje.

Iz toga možemo da generalizujemo ideju.

Now we can generalize the idea.

Umesto jedne tačke u mozgu,

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

možemo izmisliti napravu koja može obuhvatiti mozak,

koja može dopremiti svetlo u trodimenzionalnom obliku --

that can deliver light into three-dimensional patterns --

nizovi optičkih vlakana,

arrays of optical fibers,

svaki uparen sa njegovim nezavisnim minijaturnim izvorom svetla.

each coupled to its own independent miniature light source.

I tada možemo da pokušamo stvari na živo

Then we can try to do things in vivo

koje su do sada rađene samo u posudama --

that have only been done to date in a dish,

like high-throughput screening throughout the entire brain

kao što je visoko-propusno nadgledanje kompletnog mozga

zbog signala koji mogu prouzrokovati dešavanje određenih stvari.

for the signals that can cause certain things to happen

Ili bi mogli da budu dobre kliničke ciljane grupe

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

za tretmane poremećaja mozga.

Evo još jedne priče koju želim da vam ispričam

One story I want to tell you about is:

o tome kako možemo naći mete za tretman PTSP --

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

oblik nekontrolisane anksioznosti i straha.

a form of uncontrolled anxiety and fear?

Jedna od stvari koje smo uradili

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

je bila da smo usvojili veoma klasičan model straha.

This goes back to the Pavlovian days.

Ovo je iz vremena Pavlova.

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

Naziva se Pavlovljevim uslovljavanjem --

tu se zvuk završava kratkim šokom.

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

Šok nije bolan ali je neprijatan.

Tokom vremena -- u ovom slučaju miš --

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

koji je dobar životinjski model, obično se koristi u ovakvim eksperimentima --

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

životinja uči da se plaši zvuka.

the animal learns to fear the tone.

Životinja reaguje kočenjem,

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

nešto kao jelen uhvaćen u farove.

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

Pitanje je koju metu možemo da nađemo u mozgu

that allow us to overcome this fear?

koja bi nam omogućila da prevlada strah?

Stoga smo ponovo proizvodili ton

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

nakon što je povezan sa strahom.

Ali aktiviramo ciljeve u mozgu, neke druge,

But we activate different targets in the brain,

koristeći nizove optičkih vlakana o kojima sam vam pričao uz prethodni slajd,

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

u cilju da probamo da odredimo koji ciljevi

in order to try and figure out

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

mogu da učine da mozak prevaziđe sećanje na strah.

I tako ovaj kratki video snimak

This brief video shows you one of these targets

pokazuje jedan od tih ciljeva na kojima mi sada radimo.

that we're working on now.

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

Ovo je oblast u prefrontalnom korteksu,

region u kome koristimo spoznato da pokušamo da prevaziđemo averzivna emocionalna stanja.

to try to overcome aversive emotional states.

Životinja će čuti ton -- bljesak svetla se pojavio tamo.

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

Ovaj snimak nema ton ali možete videti da se životinja ukočila.

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

Ovaj ton je značio najavu lošeg.

the tone used to mean bad news.

U donjem levom uglu vidite mali sat,

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

tako da možete da vidite da je životinja u ovom stanju oko dva minuta.

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

A sada sledeći video snimak

This next clip is just eight minutes later.

koji je napravljen samo osam minuta kasnije.

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

Isti ton je proizveden i svetlo će bljesnuti ponovo.

OK, evo ga. Baš sad.

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

I sada možete videti, nakon samo deset minuta eksperimenta,

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

da smo mozgu omogućili fotoaktiviranjem oblasti

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

da prevaziđe iskazivanje

to overcome the expression of this fear memory.

sećanja na strah.

Tokom poslednjih par godina vrativši se stablu života,

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

pošto smo želeli da nađemo način da isključimo kola u mozgu.

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

Ako bi mogli to da uradimo to bi bilo izuzetno moćno.

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

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

Ako možete da izbrišete ćelije na samo nekoliko milisekundi ili sekundi,

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

možete da otkrijete koju to neophodnu ulogu one imaju

u kolu u koje su smeštene.

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

Pregledom organizama širom stabla života --

svako životno carstvo osim životinjskog jer mi vidimo nešto drugačije.

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

I našli smo svakojake vrste molekula, zovu se halorhodopsini i arherohodopsini,

We found molecules called halorhodopsins or archaerhodopsins,

koje odgovaraju na zeleno i žuto svetlo.

that respond to green and yellow light.

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

Oni rade nešto različito od molekula o kojima sam vam pričao ranije

sa channelrhodopsin-om koji se aktivira plavim svetlom.

with the blue light activator, channelrhodopsin.

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

Evo primera o tome šta mislimo kuda ovo vodi.

Consider, for example, a condition like epilepsy,

Uzmimo na primer stanje kao što je epilepsija,

where the brain is overactive.

gde je mozak previše aktivan.

Now, if drugs fail in epileptic treatment,

Ako lekovi ne uspevaju da tretiraju epilepsiju,

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

jedna od strategija je da se odstrani deo mozga.

Ali to je očigledno nepovratna akcija i moglo bi da bude neželjenih efekata.

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

Šta ako možemo da jednostavno isključimo taj mozak na tren,

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

dok napad ne prođe,

until the seizure dies away,

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

i tako uspemo da mozak obnovi svoje početno stanje --

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

nešto kao dinamički sistem koji potisnemo nadole u stabilno stanje.

Ova animacija samo pokušava da objasni koncept

This animation tries to explain this concept

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

u kome smo učinili ove ćelije osetljivim na gašenje svetlom,

i onda bljesnemo svetlo,

and we beam light in,

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

i to samo onoliko vremena koliko je potrebno da se zaustavi napad

u nadi da ćemo biti u stanju da mozak ugasimo.

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

Nemamo podatke da vam ih sada pokažemo

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

ali ovo je veoma uzbudljivo.

but we're very excited about this.

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

Želim da završim jednom pričom,

za koju mislimo da je još jedna od mogućnosti --

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

a to je da ovi molekuli možda, ako može da se napravi ultra precizno upravljanje,

mogu da budu upotrebljeni u samom mozgu

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

za pravljenje nove vrste pomagala, optičkih pomagala.

an optical prosthetic.

Već sam vam rekao da elektirčna stimulacija nije neobična.

I already told you that electrical stimulators are not uncommon.

75.000 ljudi ima, duboko u mozgu, ugrađene stimulatore za kontrolu Parkinsonove bolesti.

Seventy-five thousand people

have Parkinson's deep-brain stimulators implanted,

Nekih 100.000 ljudi ima kohlearne implante,

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

koji im omogućavaju da čuju.

Ima tu još nesšto a to je da morate da ubacite ove gene u ćelije.

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

Pojavila se nova nada u genskoj terapiji

A new hope in gene therapy has been developed,

because viruses like the adeno-associated virus --

jer su virusi poput adeno povezanih virusa,

koje verovatno većina nas u ovoj prostoriji ima,

which probably most of us around this room have;

a da pri tom nema nikakve simptome,

it doesn't have any symptoms --

upotrebljeni na stotinama pacijenata

have been used in hundreds of patients

to deliver genes into the brain or the body.

da bi dopremili gene u mozak ili telo.

And so far, there have not been serious adverse events

I za sada još nije bilo ozbiljnih štetnih događaja

koji su povezani sa virusom.

associated with the virus.

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

U sobi se nalazi još jedan slon, sami proteini,

which come from algae, bacteria and funguses

koje dobijamo od algi i bakterija i plesni,

and all over the tree of life.

sa celog stabla života.

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

Većina nas nema plesni ili alge u mozgu,

i šta će mozak da uradi ako mu ih ubacimo?

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

Da li će ih ćelije tolerisati? Da li će reagovati imunološki sistem?

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

U početku smo -- ovo još nije probano na ljudima --

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

ali radimo na raznim studijama

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

ispitujući ovo.

Za sada nismo videli suprotne ili ikakve značajne reakcije

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

na ove molekule

to these molecules

or to the illumination of the brain with light.

ili na obasjavanje mozga svetlošću.

Rano je, da budemo jasni, ali smo veoma uzbuđeni svim ovim.

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

Želim da završim jednom pričom,

I wanted to close with one story,

which we think could potentially be a clinical application.

za koju mislimo da predstavlja potencijalnu

kliničku primenu.

Now, there are many forms of blindness

Postoje razne vrste slepila

gde fotoreceptori,

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

naši svetlosni senzori koji su u dnu naših očiju, više ne postoje.

are gone.

And the retina is a complex structure.

A retina je, naravno, kompleksna struktura.

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

Hajde da zumiramo to, da bi mogli da vidimo više detalja.

Fotoreceptorske ćelije su prikazane na vrhu,

The photoreceptor cells are shown here at the top.

The signals that are detected by the photoreceptors are transformed

a onda se signal koji detektuju fotorecpetori

transformiše različitim proračunima,

via various computations

dok na kraju taj sloj ćelija na dnu, ganglionske ćelije,

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

proslede informaciju mozgu,

relay the information to the brain,

gde vidimo opaženo.

where we see that as perception.

U mnogim vrstama slepila, kao recimo retinska pigmentoza,

In many forms of blindness, like retinitis pigmentosa

or macular degeneration,

ili degeneracija makule,

the photoreceptor cells have atrophied or been destroyed.

fotorecpetorske ćelije su atrofirane ili su uništene.

Now, how could you repair this?

Kako je ovo moguće popraviti?

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

Nije jasno da lekovi mogu da uzrokuju obnavljanje,

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

pošto ne postoji ništa za šta bi lek mogao da se veže.

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

A opet, svetlo i dalje dospeva u oko.

Oko je i dalje providno i možete da uvedete svetlost unutra.

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

Šta ako možemo da uzmemo channelfhodopsin-e i druge molekule

So what if we could take these channelrhodopsins and other molecules

i instaliramo ih na neke od slobodnih ćelija

and install them on some of these other spared cells

i tako ih pretvorimo u male kamere.

and convert them into little cameras?

A pošto ima mnogo ovih ćelija u oku,

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

potencijalno, one mogu biti kamere visoke rezolucije.

potentially, they could be very high-resolution cameras.

To je nešto na čemu radimo.

This is some work that we're doing,

Time rukovodi jedan od naših saradnika,

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

Alan Horsager sa USC-a,

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

a radi komercijalizacije ga traži start-ap kompanija Eos Neuroscience,

koju je osnovao NIH.

which is funded by the NIH.

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

Ono što vidite ovde je miš koji pokušava da reši lavirint.

To je šestokraki lavirint. A ima i nešto vode u lavirintu

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

da bi motivisali miša da se kreće jer bi u suprotnom on samo sedeo unutra.

Cilj ovog lavirinta je, naravno,

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

da izađe iz vode na malu platformu

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

koja je pod osvetljenim gornjim otvorom.

Miševi su pametni, i tako ovaj miš konačno reši lavirint,

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

but he does a brute-force search.

ali on primenjuje pretragu putem pokušaja i promašaja.

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

On upliva u svako udubljenje dok na kraju ne nađe platformu.

He's not using vision to do it.

Znači ne koristi vid da bi to obavio.

These different mice are different mutations

Ovi razni miševi imaju raličite mutacije

koje prikazuju različite vrste slepila koje pogađa ljude.

that recapitulate different kinds of blindness that affect humans.

Pažljivo smo se trudili da sagledamo ove različite modele,

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

i tako smo došli do generalizovanog pristupa.

so we come up with a generalized approach.

Kako ćemo da rešimo ovo?

So how can we solve this?

Pokušaćemo da uradimo baš ono što smo predstavili prethodnim slajdom.

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

Uzećemo ove fotosenzore za plavo svetlo

We'll take these blue light photo sensors

i instaliraćemo ih na sloj ćelija

and install them onto a layer of cells

u sredini retine, u dnu oka

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

and convert them into a camera --

i pretvorićemo ih u kamere.

just like installing solar cells all over those neurons

Baš kao što se instaliraju solarne ćelije svuda po ovim neuronima

da bi ih učinili osetljivim na svetlost.

to make them light-sensitive.

Light is converted to electricity on them.

Svetlo se pretvara u elektricitet na njima.

So this mouse was blind a couple weeks before this experiment

Ovaj miš je bio slep nekoliko nedelja pre ovog eksperimenta

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

i primio je jednu dozu ovih fotoosetljivih molekula u virusu.

Kao što možete videti, životinja zaista može da izbegne zidove

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

i dođe do male platforme

and go to this little platform

ponovo upotrebivši oči za tu spoznaju.

and make cognitive use of its eyes again.

A da bih naglasio značaj ovoga:

And to point out the power of this:

ove životinje su bile u stanju da dođu na platformu

these animals can get to that platform

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

istom brzinom kao i životinje koje vide celog života.

Ova predklinička studija je, mislim,

So this preclinical study, I think, bodes hope

dobar predznak za vrstu stvari

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

za koje se nadamo da ćemo raditi u budućnosti.

Za kraj, želim da naglasim da mi istražujemo i

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

nove poslovne modele za ovo novo polje neurotehnologije.

Razvijamo oruđa,

We're developing tools and sharing them freely

ali ih razmenjujemo slobodno sa stotinama grupa širom sveta,

with hundreds of groups all over the world

tako da ljudi mogu da proučavaju i pokušavaju da tretiraju različite poremećaje.

for them to study and try to treat different disorders.

Nadamo se da, shvativši kola u mozgu

Our hope is that by figuring out brain circuits

na apstraktnom nivou koji nam dopušta da ih popravimo i da ih stvaramo,

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

možemo neke od ovih tvrdoglavih poremećaja o kojima sam ranije pričao,

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

od kojih nijedan praktično nije izlečen,

practically none of which are cured,

da pošaljemo u istoriju.

and in the 21st century, make them history.

Hvala.

Thank you.

(Applause)

(Aplauz)

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

Huan Enrikez: Nešto od ovoga je malo previše.

(Laughter)

(Smeh)

Ali implikacije

But the implications of being able to control seizures or epilepsy

ideje da je moguće kontrolisati napade ili epilepsiju

with light instead of drugs

svetlom umesto lekovima,

and being able to target those specifically

i mogućnosti da se baš one naciljaju

is a first step.

je prvi korak.

The second thing that I think I heard you say

Druga stvar koju mislim da sam čuo da si rekao

is you can now control the brain in two colors,

je da je sada moguće kontrolisati mozak dvema bojama.

Nešto kao prekidač za uključivanje i isključivanje.

like an on-off switch.

Ed Boyden: Tako je.

Ed Boyden: That's right.

HE: To svaki impuls koji ide kroz mozak čini binarnim kodom.

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

EB: Da, tako je.

EB: Right.

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

Plavim svetlom možemo slati informacije, i to je recimo jedinica.

A isključivanje je nešto kao nula.

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

Tako da se mi nadamo da ćemo moći da stvorimo koprocesore u mozgu

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

koji će raditi sa mozgom,

tako da ćemo moći da povećamo funkcije ljudima sa invaliditetom.

so we can augment functions in people with disabilities.

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

HE: U teoriji to znači da,

kao što miš oseća, omiriše,

čuje, dodirne,

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

vi možete da napravite model u vidu jedinica i nula.

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

EB: Naravno, da. Nadamo se da to upotrebimo kao način testiranja.

koji su prirodni kodovi koji upravljaju određenim ponašanjima

what neural codes can drive certain behaviors

i određenim mislima i određenim osećanjima,

and certain thoughts and certain feelings

i da to upotrebimo za bolje spoznavanje mozga.

and use that to understand more about the brain.

JE: Does that mean that someday you could download memories

HE: Da li to znači da ćemo jednog dana moći da daunlodujemo sećanja

and maybe upload them?

i možda ih aploudujemo?

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

EB: Pa to je nešto na čemu počinjemo da radimo intenzivno.

Sada radimo na radu

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

gde pokušavamo da popločamo mozak i elementima za beleženje.

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

Tako da možemo da zabeležimo informacije i onda da možemo da upravimo informacije nazad --

sort of computing what the brain needs

nešto kao proračunavanje onoga što je mozgu potrebno

in order to augment its information processing.

da bi poboljšali njegov informacioni proces.

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

HE: To bi moglo da izmeni neke stvari. Hvala ti. (EB: Hvala.)

EB: Thank you.

(Aplauz)

(Applause)