Ed Boyden: A light switch for neurons

Prevoditelj: Senzos Osijek Recezent: Tilen Pigac - EFZG

Razmislite o svom danu na sekundu.

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, osjetili svjež zrak na svom licu kad ste izašli kroz vrata,

encountered new colleagues and had great discussions

susreli nove kolege i imali odlične rasprave,

i začudili se otkrivši nešto novo.

and felt in awe when you found something new.

Ali kladim se da niste mislili o nečemu danas --

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

nečemu tako blizu domu

something so close to home,

da vjerojatno ne mislite o tome često.

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

A to je da svim osjetima, osjećajima,

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

odlukama i radnjama

upravlja računalo u vašoj glavi

are mediated by the computer in your head

zvano mozak.

called your brain.

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

Mozak možda ne izgleda posebno izvana --

nekoliko kilograma ružičastosivog mesa,

a couple pounds of pinkish-gray flesh,

amorfnog --

amorphous.

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

ali posljednjih nam je sto godina neuroznanosti

omogućilo zumiranje mozga,

and to see the intricacy of what lies within.

i proučavanje složenosti onoga što leži unutra.

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

I rekli su nam da je taj mozak

nevjerojatno složen sklop

made out of hundreds of billions of cells called neurons.

sastavljen od stotina milijarda stanica zvanih neuroni.

Now, unlike a human-designed computer,

Za razliku od računala što ih čine ljudi,

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

gdje imamo relativno malen broj različitih dijelova --

znamo kako rade, jer smo ih mi izradili --

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 tisuća različitih vrsta stanica,

možda desetaka tisuća.

maybe tens of thousands.

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

Dolaze u različitim oblicima; sačinjeni su od različitih molekula;

i projiciraju i povezuju različite regije mozga.

they project and connect to different brain regions.

I također se mijenjaju na različite načine u raznim bolestima.

They also change in different ways in different disease states.

Idemo konkretnije.

Let's make it concrete.

There's a class of cells,

Postoji klasa stanica,

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

relativno malih stanica, inhibitornih, koje utišavaju svoje susjede.

To su jedne od stanica koje se čine utišanim u stanjima poput šizofrenije.

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

in disorders like schizophrenia.

It's called the basket cell.

Zove se košarasta stanica.

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

I ta je stanica jedna od tisuća vrsta stanica

o kojima učimo.

that we're learning about.

New ones are being discovered every day.

Nove se otkrivaju svakodnevno.

I kao drugi primjer:

As just a second example:

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

ove piramidne stanice, velike stanice,

mogu obuhvatiti velik dio mozga.

of the brain.

One su ekscitatorne.

They're excitatory.

Ove stanice

And these are some of the cells that might be overactive

mogu biti previše aktivne u poremećajima poput epilepsije.

in disorders such as epilepsy.

Svaka od tih stanica

Every one of these cells is an incredible electrical device.

je nevjerojatan električni uređaj.

They receive inputs from thousands of upstream partners

Primaju podražaje od tisuća uzvodnih partnera

i izračunavaju svoje vlastite električne podražaje,

and compute their own electrical outputs,

which then, if they pass a certain threshold,

koji onda, ako prijeđu određen prag,

mogu otići do tisuća nizvodnih partnera.

will go to thousands of downstream partners.

I ovaj proces, koji obično traje 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,

događa se tisućama puta u minuti

u svakom od 100 milijardi stanica,

as long as you live and think and feel.

dokle god smo živi

i mislimo i osjećamo.

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

Kako ćemo otkriti što sklop radi?

Idealno, otišli bismo kroz sklop

Ideally, we could go through this circuit

i palili i gasili različite stanice

and turn these different kinds of cell on and off

and see whether we could figure out

i gledali možemo li shvatiti

which ones contribute to certain functions

kako pojedine stanice doprinose određenoj funkciji

and which ones go wrong in certain pathologies.

i koje su poremećene u određenim patološkim stanjima.

Kad bismo mogli aktivirati stanice, mogli bismo vidjeti koje moći one mogu osloboditi,

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

što mogu pokrenuti i kontrolirati.

what they can initiate and sustain.

Kad bismo ih ugasili,

If we could turn them off,

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

mogli bismo probati shvatiti za što su nam potrebne.

I to je priča o kojoj ću vam govoriti danas.

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

I iskreno, gdje smo sve bili u zadnjih jedanaest godina,

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

pokušavajući naći načine

through an attempt to find ways

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

paljenja i gašenja sklopova, stanica,

dijelova i puteva u mozgu,

on and off,

da bismo shvatili znanost,

both to understand the science

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

i suočili se s nekim od problema

s kojima se suočavamo kao ljudi.

Now, before I tell you about the technology,

Prije nego što vam kažem nešto o tehnologiji,

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

loša vijest je što će velik dio nas u ovoj prostoriji,

ako budemo živjeli dovoljno dugo,

if we live long enough,

will encounter, perhaps, a brain disorder.

razviti, možda, neurološki poremećaj.

Već je sad milijarda ljudi

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

imala određen oblik neurološkog poremećaja

koji ih je onesposobio.

that incapacitates them.

The numbers don't do it justice, though.

I broj ih je zakinuo.

These disorders -- schizophrenia, Alzheimer's,

Ovi poremećaji -- šizofrenija, Alzheimer,

depresija, ovisnosti --

depression, addiction --

they not only steal away our time to live,

ne kradu nam samo naše vrijeme života, već mijenjaju i ono tko smo;

they change who we are.

They take our identity and change our emotions

uzimaju nam identitet i mijenjaju naše osjećaje --

and change who we are as people.

mijenjaju ono tko smo kao ljudi.

Now, in the 20th century,

Sada u 20. stoljeću,

stvorila se nada

there was some hope that was generated

through the development of pharmaceuticals for treating brain disorders.

zbog stvaranja lijekova za liječenje poremećaja mozga.

I dok su bili razvijeni mnogi lijekovi

And while many drugs have been developed

that can alleviate symptoms of brain disorders,

koji mogu ublažiti simptome poremećaja mozga,

prakički ni jedan od njih ne možemo smatrati izliječenim.

practically none of them can be considered to be cured.

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

A to je dijelom zbog toga što kupamo mozak u kemikalijama.

we're bathing the brain in a chemical --

Ovaj je složeni sklop

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

napravljen od tisuća različitih vrsta stanica

koje mi kupamo u raznim tvarima.

is being bathed in a substance.

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

To je i razlog zbog kojeg možda većina lijekova na tržištu, ako ne i svi,

imaju neke vrste ozbiljnih, neželjenih posljedica.

can present some kind of serious side effect too.

Neki ljudi dobili su nekakvo olakšanje

Now some people have gotten some solace from electrical stimulators

u električnim stimulatorima koji su im ugrađeni u mozak.

that are implanted in the brain,

for Parkinson's disease or cochlear implants.

I za Parkinsonovu su bolest

kohlearni implantanti

These have indeed been able to bring some kind of remedy

zaista postigli

neka poboljšanja

to people with certain kinds of disorders.

kod ljudi s određenim vrstama poremećaja.

But electricity also will go in all directions --

Ali elektricitet ide u svim smjerovima --

the path of least resistance --

putem manjeg otpora,

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

odakle taj izraz djelomice i dolazi.

and will also affect normal circuits,

I utjecat će na normalne sklopove, kao i na one abnormalne koje želite popraviti.

as well as the abnormal ones you want to fix.

Dakle, opet smo se vratili na ideju

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

ultraprecizne kontrole.

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

Možemo li usmjeriti informaciju točno tamo kamo želimo da ode?

I tako, kada sam se počeo baviti neuroznanošću prije 11 godina,

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

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

bio sam školovan kao električni inžinjer i fizičar

the first thing I thought about was,

i prva stvar na koju sam pomislio jest da,

if these neurons are electrical devices,

ako su ovi neuroni električne naprave,

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

sve što moramo napraviti jest naći neki način

da provedemo te električne promjene s daljine.

at a distance.

Kad bismo mogli izazvati elektricitet u jednoj stanici,

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

ali ne u njezinim susjedama,

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

to bi nam dalo alat kojim bismo mogli aktivirati i ugasiti te različite stanice,

otkriti što one rade i kako doprinose

to figure out what they do

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

mrežama u koje su uključene.

To bi nam također omogućilo da imamo ultrapreciznu kontrolu koju trebamo

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

kako bismo popravili rezultate sklopova

to fix the circuit computations that have gone awry.

koji su pošli po krivu.

Now, how are we going to do that?

Kako ćemo to učiniti?

Well, there are many molecules that exist in nature

Pa, u prirodi postoji mnogo molekula

koje su sposobne pretvoriti svjetlost u elektricitet.

which are able to convert light into electricity.

Možete o njima razmišljati 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,

Kada bismo nekako mogli instalirati te molekule u neurone,

then these neurons would become electrically drivable with light,

tada bi ti neuroni postali električno upravljivi svjetlom.

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

A njihovi susjedi koji nemaju tu molekulu ne bi to bili.

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

Postoji još jedan magični trik koji vam treba kako bi se sve to dogodilo,

a to je sposobnost uvođenja svjetla u mozak.

the ability to get light into the brain.

The brain doesn't feel pain.

Da biste to učinili -- mozak ne osjeća bol -- možete staviti --

Taking advantage of all the effort

koristeći prednosti svih napora

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

koji su uloženi u internet i komunikacije itd.--

you can put optical fibers connected to lasers

optička sredstva povezana laserima

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

koja možete koristiti da aktivirate, u životinjskim primjerima npr.

u predkliničkim istraživanjima,

these neurons and see what they do.

te neurone i da vidite što oni rade.

Pa kako ćemo to učiniti?

So how do we do this?

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

Otprilike 2004.,

u suradnji s Gerhard Nagelom i Karlom Deisserothom,

this vision came to fruition.

ta je vizija donijela plodove.

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

Postoji određena alga koja pliva u divljini

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

i mora navigirati prema svjetlu,

kako bi optimalno fotosintetizirala.

And it senses light with a little eyespot,

Ona osjeća svjetlo pomoću male oko-točke

which works not unlike how our eye works.

koja funkcionira slično našem oku.

In its membrane, or its boundary,

U njezinoj membrani (ili njezinoj granici)

it contains little proteins

sadrži male proteine

koji zaista pretvaraju svjetlost u elektricitet.

that indeed can convert light into electricity.

Te se molekule zovu channelrhodopsini.

These molecules are called channelrhodopsins.

And each of these proteins acts just like that solar cell

Svaki se od tih proteina ponaša baš kao solarna ćelija o kojoj sam vam govorio.

that I told you about.

Kada ju pogodi plavo svjetlo, ona otvori malu rupu

When blue light hits it,

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

i dozvoli nabijenim česticama da uđu u oko-točku.

To dopušta toj oko-točki da ima električni signal

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

Dakle, ono što trebamo napraviti jest uzeti te molekule

i nekako ih instalirati u neurone.

and somehow install them in neurons.

And because it's a protein,

Budući da je to protein,

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

kodiran je za DNK svog organizma.

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

Dakle, sve što trebamo napraviti jest uzeti taj DNK,

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

staviti ga u okvir genske terapije kao virus

and put it into neurons.

i postaviti ga u neurone.

And this was a very productive time in gene therapy,

Ispalo je da je to bilo veoma produktivno vrijeme u genskoj terapiji

and lots of viruses were coming along,

pa se pojavljivalo mnogo virusa

so this turned out to be fairly simple.

te se ispostavilo da je to veoma jednostavno napraviti.

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

Rano ujutro jednog ljetnog dana 2004.

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

pokušali smo i upalilo je iz prvog pokušaja.

Uzmete taj DNK i stavite ga u neuron.

You take this DNA and put it into the neuron.

The neuron uses its natural protein-making machinery

Neuron koristi svoj prirodni protein, tvoreći mašineriju

to fabricate these little light-sensitive proteins

za proizvodnju tih malih proteina osjetljivih na svjetlost

i njihovo instaliranje po cijeloj stanici

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

poput postavljanja solarnih panela na krovu.

And the next thing you know,

I u sljedećem trenutku

you have a neuron which can be activated with light.

imate neuron koji može biti aktiviran pomoću svjetla.

Dakle, to je veoma moćno.

So this is very powerful.

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

Jedan od trikova koje morate napraviti

jest shvatiti kako dostaviti te gene u one stanice koje želite,

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

a ne u ostale, susjedne stanice.

I to možete napraviti; možete oblikovati viruse

And you can do that;

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

da pogode samo one određene stanice.

Postoje i drugi genetički trikovi koje možete iskoristiti

And there's other genetic tricks you can play

kako biste dobili stanice koje se aktiviraju svjetlom.

in order to get light-activated cells.

To je polje postalo poznato 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,

I kao samo jedan primjer onoga što možete napraviti,

možete uzeti kompleksnu mrežu,

you can take a complex network,

use one of these viruses to deliver the gene

iskoristiti jedan od ovih virusa da dostave gene

određenoj vrsti stanica u ovoj gustoj mreži.

just to one kind of cell in this dense network.

And then when you shine light on the entire network,

I tada, kada osvjetlite cijelu mrežu,

just that cell type will be activated.

aktivirat će se samo taj tip stanica.

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

Pa na primjer, hajdemo uzeti u obzir onu košarastu stanicu o kojoj sam vam govorio ranije --

onu koja je zakržljala u slučaju šizofrenije

the one that's atrophied in schizophrenia

i koja je inhibicijska.

and the one that is inhibitory.

Ako možete dostaviti taj gen u te stanice --

If we can deliver that gene to these cells --

one neće biti izmijenjene u genetskom smislu, naravno --

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

i tada bljesnete plavim svjetlom preko cijele mreže mozga,

then flash blue light over the entire brain network,

just these cells are going to be driven.

samo će te stanice biti pokrenute.

Kada se svjetlo ugasi, stanice se vrate u normalno stanje;

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

dakle, čini se da se one ne protive tome.

there don't seem to be adverse events.

Not only can you study what these cells do,

Ne samo da možete to iskoristiti kako biste proučavali što te stanice mogu

what their power is in computing in the brain,

i koja je njihova moć u računanju mozga

već i to možete iskoristiti kako biste shvatili --

you can also use this to try to figure out

pa možda biste mogli oživjeti aktivnost tih stanica

if we could jazz up the activity of these cells

ako one zaista jesu atrofirane.

if indeed, they're atrophied.

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

Sada vam želim ispričati nekoliko kratkih priča

o tome kako to koristimo

both at the scientific clinical and preclinical levels.

i na znanstvenim, kliničkim i predkliničkim razinama.

One of the questions that we've confronted is:

Jedno od pitanja s kojima smo suočeni jest:

What signals in the brain mediate the sensation of reward?

„Koji signali u mozgu posreduju pri osjećaju nagrađenosti?“

Because if you could find those,

Jer, kada bismo ih mogli pronaći,

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

oni bi mogli biti neki od signala koji bi mogli upravljati učenjem.

Mozak bi radio više onog što dovodi do te nagrade.

the brain will do more of what got that reward.

Također, postoje signali koji se iskrive u poremećajima poput ovisnosti.

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

Pa, kada bismo mogli shvatiti koje su to stanice,

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

možda bismo mogli pronaći nove mete

za koje bi lijekovi mogli biti dizajnirani ili ograđeni od njih

for which drugs can be designed or screened against

ili možda mjesta gdje bi elektrode mogle biti postavljene

or maybe places where electrodes could be put in

za ljude koji imaju veoma ozbiljan invaliditet.

for people who have severe disability.

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

Kako bismo to napravili, smislili smo veoma jednostavnu paradigmu

u suradnji s Fiorella grupom,

in collaboration with the Fiorillo group,

gdje jedna strana ove male kutije,

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

ako životinja ode tamo, životinja dobije puls svjetla,

it gets a pulse of light.

kako bi se određene stanice u mozgu učinile osjetljivima na svjetlo.

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

Ako te stanice mogu posredovati nagrađivanjem,

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

životinja bi trebala tamo odlaziti sve više i više.

I to je ono što se događa.

And that's what happens.

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

Ova će životinja otići u desnu stranu i dotaknuti svoj nos tamo;

ona dobije bljesak plavog svjetla svaki put kada to napravi.

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

I učinit će to stotinama i stotinama puta.

He'll do that hundreds of times.

To su neuroni dopamina,

These are the dopamine neurons,

o kojima ste možda nešto čuli slušajući o centrima za užitak koji se nalaze u mozgu.

in some of the pleasure centers in the brain.

Sada smo pokazali da je njihova kratka aktivacija

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

zaista dovoljna da stimulira učenje.

Sada možemo tu ideju generalizirati.

Now we can generalize the idea.

Umjesto jedne točke u mozgu,

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

možemo izumiti naprave koje obuhvaćaju cijeli mozak,

koje mogu provesti svjetlo u trodimenzionalnim modelima --

that can deliver light into three-dimensional patterns --

mnoštvo optičkih vlakana,

arrays of optical fibers,

svaki sparen u vlastiti, minijaturni svjetlosni izvor.

each coupled to its own independent miniature light source.

I tada možemo probati učiniti uživo stvari

Then we can try to do things in vivo

koje su dosad bile rađene samo u posudama --

that have only been done to date in a dish,

like high-throughput screening throughout the entire brain

poput visokopropusnog skeniranja cijelog mozga

za signale koji mogu uzrokovati određene stvari.

for the signals that can cause certain things to happen

Ili mogu biti dobre kliničke mete

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

za liječenje moždanih poremećaja.

Jedna priča koju vam želim ispričati

One story I want to tell you about is:

je o tome kako pronalazimo mete za liječenje posttraumatskog stresnog poremećaja --

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

oblika nekontrolirane anksioznosti i straha.

a form of uncontrolled anxiety and fear?

Jedna od stvari koju smo napravili

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

jest da smo prilagodili klasičan model straha.

This goes back to the Pavlovian days.

Ovo odlazi natrag u doba Ivana Pavlova.

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

Zove se Pavlovo uvjetovanje strahom --

gdje ton završava kratkim šokom.

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

Šok nije bolan, ali je pomalo iritantan.

I nakon nekog vremena -- u ovom slučaju miš,

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

koji je dobra životinja za model, često korištena u takvim eksperimentima --

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

životinja se nauči bojati tona.

the animal learns to fear the tone.

Životinja će reagirati zamrzavanjem,

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

pomalo kao jelen ispred prednjih svjetala.

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

Pitanje je koje mete u mozgu možemo naći,

that allow us to overcome this fear?

a da će nam dopustiti da nadvladamo ovaj strah?

Ono što činimo jest puštanje toga tona ponovno,

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

nakon što je bio povezan sa strahom.

Ali aktiviramo mete u mozgu, neke druge,

But we activate different targets in the brain,

koristeći mnoštvo optičkih vlakana o kojima sam vam govorio na prošlom slajdu,

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

kako bismo pokušali shvatiti koje mete u mozgu

in order to try and figure out

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

mogu uzrokovati nadvladavanje tog sjećanja straha.

Tako vam ovaj kratak video

This brief video shows you one of these targets

pokazuje jednu od tih meta na kojima trenutno radimo.

that we're working on now.

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

Ovo je područje u prefrontalnom korteksu,

u regiji gdje saznanja možemo iskoristiti, kako bismo pokušali premostiti neželjena emotivna stanja.

to try to overcome aversive emotional states.

Životinja će čuti ton -- i bljesak svjetla se ondje dogodi.

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

Nema zvuka na ovome, ali možete vidjeti životinju kako se zaustavlja.

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

Ovaj ton značio je prije loše vijesti.

the tone used to mean bad news.

Ondje je mali sat u donjem lijevom kutu

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

pa možete vidjeti da je životinja otprilike dvije minute u tome.

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

Sada je ova snimka

This next clip is just eight minutes later.

samo osam minuta kasnije.

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

Isti ton bit će pušten i svjetlo će opet bljesnuti.

Ok, evo ga. Upravo sada.

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

I sada možete vidjeti, u samo deset minuta eksperimenta,

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

da smo opremili mozak aktivirajući ovo područje svjetlom,

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

kako bismo premostili ovo sjećanje

to overcome the expression of this fear memory.

na osjećaj straha.

Tijekom zadnjih nekoliko godina vratili smo se stablu života

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

jer smo željeli pronaći načine za isključivanje sklopova u mozgu.

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

Kad bismo to mogli, bilo bi to veoma moćno.

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

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

Kad bismo mogli poništiti stanice samo na milisekundu ili sekunde,

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

mogli bismo shvatiti kakvu nužnu ulogu one igraju

u sklopovima u koje su uključene.

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

I sad smo preispitali organizme sa svih razina stabla života --

svako carstvo života, osim životinja, vidimo malo drugačije.

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

Našli smo razne vrste molekula koje se zovu halorodopsini ili arhearodopsini,

We found molecules called halorhodopsins or archaerhodopsins,

a koje reagiraju na zeleno i žuto svjetlo.

that respond to green and yellow light.

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

One čine suprotnu stvar od molekule s aktivatorom plavog svjetla

channelrodopsinom, o kojoj sam vam pričao ranije.

with the blue light activator, channelrhodopsin.

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

Hajdemo dati primjer za ono što mislimo kamo će sve ovo otići.

Consider, for example, a condition like epilepsy,

Razmotrite, na primjer, stanje poput epilepsije,

where the brain is overactive.

gdje je mozak pretjerano aktivan.

Now, if drugs fail in epileptic treatment,

Ako lijekovi zakažu u tretiranju epilepsije,

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

jedna je od strategija da se ukloni dio mozga.

Ali to je očito nepovratno i moguće su neželjene posljedice.

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

Što ako bismo mogli jednostavno isključiti taj mozak na kratko vrijeme,

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 vratiti mozak u početno stanje --

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

pomalo kao dinamični sistem koji je primoran natrag u stabilno stanje.

Dakle, ta animacija samo pokušava objasniti taj koncept

This animation tries to explain this concept

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

u kojem smo stanice učinili osjetljivima na gašenje svjetlom

i tada usmjerili svjetlo unutra

and we beam light in,

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

samo za vrijeme potrebno da se napad zaustavi;

nadamo se da ćemo ga moći ugasiti.

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

Nemamo podatke za pokazati vam u vezi toga,

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

ali smo jako uzbuđeni zbog toga.

but we're very excited about this.

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

Sada želim završiti s jednom pričom,

za koju mislimo da je druga mogućnost --

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

a to je da možda te molekule, ako možete koristiti preciznu kontrolu,

mogu biti korištene u samom mozgu,

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

kako bi napravile novu vrstu prostetike, optičku prostetiku.

an optical prosthetic.

Već sam vam rekao da električni stimulatori nisu neobični.

I already told you that electrical stimulators are not uncommon.

Sedamdeset pet tisuća ljudi ima ugrađene stimulatore duboko u mozgu za Parkinsonovu bolest.

Seventy-five thousand people

have Parkinson's deep-brain stimulators implanted,

Možda 100.000 ljudi ima kohlearne implantante

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

koji im omogućuju da čuju.

I još jedna stvar, a to je da morate nekako dopremiti te gene u stanice.

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

Nova nada u genskoj terapiji bila je razvijena

A new hope in gene therapy has been developed,

because viruses like the adeno-associated virus --

zbog virusa poput adenovirusa,

koji vjerojatno ima većina nas u ovoj prostoriji,

which probably most of us around this room have;

a za koji ne postoje nikakvi simptomi

it doesn't have any symptoms --

koji su korišteni u stotinama pacijenata,

have been used in hundreds of patients

to deliver genes into the brain or the body.

kako bi se geni izručili u mozak ili tijelo.

And so far, there have not been serious adverse events

Dosada nije bilo ozbiljnijih štetnih događaja

povezanih s virusom.

associated with the virus.

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

Postoji još jedan slon u prostoriji, sami proteini,

which come from algae, bacteria and funguses

koji dolaze od algi, bakterija, gljiva

and all over the tree of life.

i drugih vrsta živih bića.

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

Većina nas nema gljiva ili algi u svom mozgu,

dakle, što će naš mozak učiniti ako to unesemo unutra?

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

Hoće li stanice to tolerirati? Hoće li reagirati imunološki sustav?

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

U ranim danima -- i ovi nisu bili provedeni na ljudima još uvijek --

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

ali radili smo na mnogo različitih studija

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

kako bismo to ispitali.

Dosad nismo vidjeli očite reakcije bilo kakve jačine

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

na te molekule

to these molecules

or to the illumination of the brain with light.

ili osvjetljenje mozga svjetlom.

Dakle, to su rani stadiji, da budemo iskreni, ali veoma smo uzbuđeni zbog toga.

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

Želio sam završiti s jednom pričom,

I wanted to close with one story,

which we think could potentially be a clinical application.

za koju smatramo da bi potencijalno

mogla biti klinička aplikacija.

Now, there are many forms of blindness

Postoje mnogi oblici sljepoće

gdje fotoreceptori,

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

naši svjetlosni senzori koji su u stražnjem dijelu oka, ne funkcioniraju.

are gone.

And the retina is a complex structure.

I mrežnica je, dakako, kompleksna struktura.

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

Hajdemo ju ovdje zumirati, kako bismo ju detaljnije vidjeli.

Stanice fotoreceptora pokazane su na vrhu

The photoreceptor cells are shown here at the top.

The signals that are detected by the photoreceptors are transformed

i tada signali koji su detektirani fotoreceptorima

bivaju transformirani raznim komputacijama,

via various computations

dok napokon taj sloj stanica na dnu, stanice ganglija,

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

ne prenesu informaciju mozgu,

relay the information to the brain,

gdje mi to vidimo kao percepciju.

where we see that as perception.

U mnogim oblicima sljepoće, poput retinitis pigmentoze

In many forms of blindness, like retinitis pigmentosa

or macular degeneration,

ili degeneracije makule,

the photoreceptor cells have atrophied or been destroyed.

fotoreceptori su zakržljali ili su uništeni.

Now, how could you repair this?

Kako bi se to moglo popraviti?

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

Čak nije ni jasno bi li se lijek mogao koristiti da se to vrati

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

jer ne postoji ništa za što bi se lijek vezao.

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

S druge strane, svjetlost još uvijek može ući u oko.

Oko je još uvijek prozirno i u njega možete uvesti svjetlo.

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

Dakle, što ako bismo mogli jednostavno uzeti te channelrodopsine i druge molekule

So what if we could take these channelrhodopsins and other molecules

i postaviti ih na neke od tih preostalih, rezervnih stanica

and install them on some of these other spared cells

i pretvoriti ih u male kamere?

and convert them into little cameras?

Zbog postojanja mnoštva tih stanica u oku,

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

potencijalno, to bi mogle biti visokorezolucijske kamere.

potentially, they could be very high-resolution cameras.

Ovo je nešto od posla kojim smo se bavili.

This is some work that we're doing,

Vodi ga jedan od naših suradnika,

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

Alan Horsager s USC-a,

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

a nova tvrtka Eos Neuroznanost, osnovana od strane

NIH-a (Nacionalnih instituta za zdravlje) ga traži za komercijalizaciju.

which is funded by the NIH.

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

Ovdje vidite miša koji pokušava proći labirintom.

To je labirint sa šest rukavaca. Tamo je malo vode u labirintu,

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

kako bi se miša motiviralo da se kreće, inače će samo sjediti ondje.

Cilj ovog labirinta jest, naravno,

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

izaći iz vode i otići na malu platformu

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

koja je ispod osvjetljenog ulaza.

Miševi su pametni pa ovaj miš na kraju rješava labirint,

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

but he does a brute-force search.

ali ga pretražuje grubom silom.

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

On pliva svakim prolazom dok na kraju napokon ne dođe do platforme.

He's not using vision to do it.

Ne koristi se vidom.

These different mice are different mutations

Ovi različiti miševi predstavljaju razne mutacije

koje oslikavaju različite vrste sljepoće koje pogađaju ljude.

that recapitulate different kinds of blindness that affect humans.

Zato oprezno pregledavamo te različite modele,

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

kako bismo došli do općeg pristupa.

so we come up with a generalized approach.

Dakle, kako ćemo ovo riješiti?

So how can we solve this?

Učinit ćemo upravo ono što smo naznačili na posljednjem slajdu.

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

Uzet ćemo te fotosenzore plavog svjetla

We'll take these blue light photo sensors

i postaviti ih na sloj stanica

and install them onto a layer of cells

na sredini mrežnice u stražnjem dijelu oka

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

and convert them into a camera --

i pretvorit ćemo ih u kameru.

just like installing solar cells all over those neurons

Baš poput instaliranja solarnih ćelija po tim neuronima

kako bismo ih učinili osjetljivima na svjetlost.

to make them light-sensitive.

Light is converted to electricity on them.

Na njima je svjetlost pretvorena u elektricitet.

So this mouse was blind a couple weeks before this experiment

Dakle, ovaj je miš bio slijep nekoliko tjedana prije pokusa

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

i primio je jednu dozu tih molekula osjetljivih na svjetlo u virusu.

Sada možete vidjeti: životinja zaista može izbjegavati zidove

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

i otići na tu malu platformu

and go to this little platform

i ponovno svjesno koristiti svoje oči.

and make cognitive use of its eyes again.

Još jedan plus u tome:

And to point out the power of this:

ove životinje mogu doći do platforme

these animals can get to that platform

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

jednako brzo kao životinje koje vide cijeli život.

Dakle, ovo je predklinička nauka. Mislim,

So this preclinical study, I think, bodes hope

mnogi se nadaju onim stvarima

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

koje ćemo jedanput, nadamo se, i mi moći činiti.

Da završim, želio bih istaknuti da također istražujemo

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

nove poslovne modele za ovo novo polje neurotehnologije.

Razvijamo ova oruđa,

We're developing tools and sharing them freely

ali dijelimo ih besplatno sa stotinama grupa diljem svijeta,

with hundreds of groups all over the world

kako bi ljudi mogli proučavati i liječiti različite poremećaje.

for them to study and try to treat different disorders.

Nadamo se da ćemo, shvaćajući moždane sklopove

Our hope is that by figuring out brain circuits

na razini apstrakcije koja nam dozvoljava da ih popravljamo i njima upravljamo,

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

moći uzeti neke od neukrotivih poremećaja, o kojima sam vam ranije govorio,

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

od kojih praktički nijedan nije izliječen,

practically none of which are cured,

i u 21. stoljeću ih učiniti prošlošću.

and in the 21st century, make them history.

Hvala vam.

Thank you.

(Applause)

(Pljesak)

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

Juan Enriquez: Dakle, neke od ovih stvari malo su guste.

(Laughter)

(Smijeh)

Ali implikacije

But the implications of being able to control seizures or epilepsy

mogućnosti da se kontroliraju napadi epilepsije

with light instead of drugs

sa svjetlom, umjesto s lijekovima,

and being able to target those specifically

i da se posebno ciljaju

is a first step.

jest prvi korak.

The second thing that I think I heard you say

Sljedeći, mislim da sam vas tako čuo,

is you can now control the brain in two colors,

jest taj da sada možete kontrolirati mozak u dvjema bojama.

Poput prekidača upali-ugasi.

like an on-off switch.

Ed Boyden: Tako je.

Ed Boyden: That's right.

JE: Što svaki impuls koji prolazi mozgom čini binarnim kodom.

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

EB: Tako je, da.

EB: Right.

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

Dakle, plavim svjetlom možemo provesti informacije i to je u obliku jedinice.

Isključujući stvari, to je više-manje nula.

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

Dakle, nadamo se da ćemo na kraju izgraditi koprocesore

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

u mozgu koji s njim surađuju,

kako bismo mogli povećati funkcije kod ljudi s invaliditetom.

so we can augment functions in people with disabilities.

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

JE: A u teoriji to znači da,

dok miš osjeća, miriše,

sluša, dodiruje,

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

možete modulirati kao niz jedinica i nula.

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

EB: Svakako, da. Nadamo se da ćemo to koristiti kao način testiranja

koji neutralni kodovi mogu pokrenuti određena ponašanja,

what neural codes can drive certain behaviors

određene misli i određene osjećaje,

and certain thoughts and certain feelings

i iskoristiti to kako bismo bolje razumjeli mozak.

and use that to understand more about the brain.

JE: Does that mean that someday you could download memories

JE: Znači li to da ćemo jednog dana moći „skinuti“ sjećanja

and maybe upload them?

i možda ih postavljati?

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

EB. Pa to je nešto na čemu počinjemo veoma marljivo raditi.

Sada radimo na nečemu

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

gdje pokušavamo pokriti mozak također elementima snimača.

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

Tako možemo snimiti informacije i tada ih opet provesti unutra --

sort of computing what the brain needs

poput računanja onoga što mozak treba,

in order to augment its information processing.

kako bismo poboljšali procesuiranje informacija.

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

JE. Pa, to bi moglo promijeniti neke stvari. Hvala vam. (EB: Hvala vama.)

EB: Thank you.

(Pljesak)

(Applause)