TED2011
Ed Boyden: A light switch for neurons
Ed Boyden: Prekidač za neurone
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Ed Boyden pokazuje kako, unoseći gene za proteine osjetljive na svjetlo u neurone mozga, može selektivno aktivirati ili deaktivirati specifične neurone pomoću umetaka optičkih vlakana. S ovom nečuvenom razinom kontrole, uspio je izliječiti miševe od analoga PTSP-a i određenih oblika sljepoće. Na pomolu su neuralne proteze. Nakon govora, voditelj Juan Enriquez vodi kratko odgovaranje na postavljena pitanja.
Ed Boyden - Neuroengineer
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute. Full bio
Ed Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute. Full bio
Double-click the English transcript below to play the video.
00:15
Think about your day for a second.
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Razmislite o svom danu na sekundu.
00:17
You woke up, felt fresh air on your face as you walked out the door,
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Probudili ste se, osjetili svjež zrak na svom licu kad ste izašli kroz vrata,
00:20
encountered new colleagues and had great discussions,
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susreli nove kolege i imali odlične rasprave,
00:22
and felt in awe when you found something new.
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i začudili se otkrivši nešto novo.
00:24
But I bet there's something you didn't think about today --
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Ali kladim se da niste mislili o nečemu danas --
00:26
something so close to home
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nečemu tako blizu domu
00:28
that you probably don't think about it very often at all.
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da vjerojatno ne mislite o tome često.
00:30
And that's that all the sensations, feelings,
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A to je da svim osjetima, osjećajima,
00:32
decisions and actions
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odlukama i radnjama
00:34
are mediated by the computer in your head
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upravlja računalo u vašoj glavi
00:36
called the brain.
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zvano mozak.
00:38
Now the brain may not look like much from the outside --
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Mozak možda ne izgleda posebno izvana --
00:40
a couple pounds of pinkish-gray flesh,
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nekoliko kilograma ružičastosivog mesa,
00:42
amorphous --
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amorfnog --
00:44
but the last hundred years of neuroscience
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ali posljednjih nam je sto godina neuroznanosti
00:46
have allowed us to zoom in on the brain,
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omogućilo zumiranje mozga,
00:48
and to see the intricacy of what lies within.
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i proučavanje složenosti onoga što leži unutra.
00:50
And they've told us that this brain
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I rekli su nam da je taj mozak
00:52
is an incredibly complicated circuit
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nevjerojatno složen sklop
00:54
made out of hundreds of billions of cells called neurons.
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sastavljen od stotina milijarda stanica zvanih neuroni.
00:58
Now unlike a human-designed computer,
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Za razliku od računala što ih čine ljudi,
01:01
where there's a fairly small number of different parts --
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gdje imamo relativno malen broj različitih dijelova --
01:03
we know how they work, because we humans designed them --
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znamo kako rade, jer smo ih mi izradili --
01:06
the brain is made out of thousands of different kinds of cells,
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mozak se sastoji od tisuća različitih vrsta stanica,
01:09
maybe tens of thousands.
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možda desetaka tisuća.
01:11
They come in different shapes; they're made out of different molecules.
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Dolaze u različitim oblicima; sačinjeni su od različitih molekula;
01:13
And they project and connect to different brain regions,
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i projiciraju i povezuju različite regije mozga.
01:16
and they also change different ways in different disease states.
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I također se mijenjaju na različite načine u raznim bolestima.
01:19
Let's make it concrete.
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Idemo konkretnije.
01:21
There's a class of cells,
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Postoji klasa stanica,
01:23
a fairly small cell, an inhibitory cell, that quiets its neighbors.
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relativno malih stanica, inhibitornih, koje utišavaju svoje susjede.
01:26
It's one of the cells that seems to be atrophied in disorders like schizophrenia.
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To su jedne od stanica koje se čine utišanim u stanjima poput šizofrenije.
01:30
It's called the basket cell.
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Zove se košarasta stanica.
01:32
And this cell is one of the thousands of kinds of cell
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I ta je stanica jedna od tisuća vrsta stanica
01:34
that we are learning about.
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o kojima učimo.
01:36
New ones are being discovered everyday.
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Nove se otkrivaju svakodnevno.
01:38
As just a second example:
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I kao drugi primjer:
01:40
these pyramidal cells, large cells,
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ove piramidne stanice, velike stanice,
01:42
they can span a significant fraction of the brain.
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mogu obuhvatiti velik dio mozga.
01:44
They're excitatory.
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One su ekscitatorne.
01:46
And these are some of the cells
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Ove stanice
01:48
that might be overactive in disorders such as epilepsy.
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mogu biti previše aktivne u poremećajima poput epilepsije.
01:51
Every one of these cells
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Svaka od tih stanica
01:53
is an incredible electrical device.
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je nevjerojatan električni uređaj.
01:56
They receive input from thousands of upstream partners
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Primaju podražaje od tisuća uzvodnih partnera
01:58
and compute their own electrical outputs,
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i izračunavaju svoje vlastite električne podražaje,
02:01
which then, if they pass a certain threshold,
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koji onda, ako prijeđu određen prag,
02:03
will go to thousands of downstream partners.
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mogu otići do tisuća nizvodnih partnera.
02:05
And this process, which takes just a millisecond or so,
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I ovaj proces, koji obično traje samo milisekundu,
02:08
happens thousands of times a minute
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događa se tisućama puta u minuti
02:10
in every one of your 100 billion cells,
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u svakom od 100 milijardi stanica,
02:12
as long as you live
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dokle god smo živi
02:14
and think and feel.
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i mislimo i osjećamo.
02:17
So how are we going to figure out what this circuit does?
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Kako ćemo otkriti što sklop radi?
02:20
Ideally, we could go through the circuit
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Idealno, otišli bismo kroz sklop
02:22
and turn these different kinds of cell on and off
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i palili i gasili različite stanice
02:25
and see whether we could figure out
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i gledali možemo li shvatiti
02:27
which ones contribute to certain functions
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kako pojedine stanice doprinose određenoj funkciji
02:29
and which ones go wrong in certain pathologies.
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i koje su poremećene u određenim patološkim stanjima.
02:31
If we could activate cells, we could see what powers they can unleash,
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Kad bismo mogli aktivirati stanice, mogli bismo vidjeti koje moći one mogu osloboditi,
02:34
what they can initiate and sustain.
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što mogu pokrenuti i kontrolirati.
02:36
If we could turn them off,
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Kad bismo ih ugasili,
02:38
then we could try and figure out what they're necessary for.
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mogli bismo probati shvatiti za što su nam potrebne.
02:40
And that's a story I'm going to tell you about today.
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I to je priča o kojoj ću vam govoriti danas.
02:43
And honestly, where we've gone through over the last 11 years,
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I iskreno, gdje smo sve bili u zadnjih jedanaest godina,
02:46
through an attempt to find ways
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pokušavajući naći načine
02:48
of turning circuits and cells and parts and pathways of the brain
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paljenja i gašenja sklopova, stanica,
02:50
on and off,
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dijelova i puteva u mozgu,
02:52
both to understand the science
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da bismo shvatili znanost,
02:54
and also to confront some of the issues
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i suočili se s nekim od problema
02:57
that face us all as humans.
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s kojima se suočavamo kao ljudi.
03:00
Now before I tell you about the technology,
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Prije nego što vam kažem nešto o tehnologiji,
03:03
the bad news is that a significant fraction of us in this room,
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loša vijest je što će velik dio nas u ovoj prostoriji,
03:06
if we live long enough,
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ako budemo živjeli dovoljno dugo,
03:08
will encounter, perhaps, a brain disorder.
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razviti, možda, neurološki poremećaj.
03:10
Already, a billion people
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Već je sad milijarda ljudi
03:12
have had some kind of brain disorder
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imala određen oblik neurološkog poremećaja
03:14
that incapacitates them,
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koji ih je onesposobio.
03:16
and the numbers don't do it justice though.
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I broj ih je zakinuo.
03:18
These disorders -- schizophrenia, Alzheimer's,
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Ovi poremećaji -- šizofrenija, Alzheimer,
03:20
depression, addiction --
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depresija, ovisnosti --
03:22
they not only steal our time to live, they change who we are.
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ne kradu nam samo naše vrijeme života, već mijenjaju i ono tko smo;
03:25
They take our identity and change our emotions
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uzimaju nam identitet i mijenjaju naše osjećaje --
03:27
and change who we are as people.
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mijenjaju ono tko smo kao ljudi.
03:30
Now in the 20th century,
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Sada u 20. stoljeću,
03:33
there was some hope that was generated
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stvorila se nada
03:36
through the development of pharmaceuticals for treating brain disorders,
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zbog stvaranja lijekova za liječenje poremećaja mozga.
03:39
and while many drugs have been developed
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I dok su bili razvijeni mnogi lijekovi
03:42
that can alleviate symptoms of brain disorders,
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koji mogu ublažiti simptome poremećaja mozga,
03:44
practically none of them can be considered to be cured.
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prakički ni jedan od njih ne možemo smatrati izliječenim.
03:47
And part of that's because we're bathing the brain in the chemical.
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A to je dijelom zbog toga što kupamo mozak u kemikalijama.
03:50
This elaborate circuit
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Ovaj je složeni sklop
03:52
made out of thousands of different kinds of cell
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napravljen od tisuća različitih vrsta stanica
03:54
is being bathed in a substance.
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koje mi kupamo u raznim tvarima.
03:56
That's also why, perhaps, most of the drugs, and not all, on the market
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To je i razlog zbog kojeg možda većina lijekova na tržištu, ako ne i svi,
03:58
can present some kind of serious side effect too.
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imaju neke vrste ozbiljnih, neželjenih posljedica.
04:01
Now some people have gotten some solace
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Neki ljudi dobili su nekakvo olakšanje
04:04
from electrical stimulators that are implanted in the brain.
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u električnim stimulatorima koji su im ugrađeni u mozak.
04:07
And for Parkinson's disease,
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I za Parkinsonovu su bolest
04:09
Cochlear implants,
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kohlearni implantanti
04:11
these have indeed been able
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zaista postigli
04:13
to bring some kind of remedy
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neka poboljšanja
04:15
to people with certain kinds of disorder.
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kod ljudi s određenim vrstama poremećaja.
04:17
But electricity also will go in all directions --
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Ali elektricitet ide u svim smjerovima --
04:19
the path of least resistance,
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putem manjeg otpora,
04:21
which is where that phrase, in part, comes from.
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odakle taj izraz djelomice i dolazi.
04:23
And it also will affect normal circuits as well as the abnormal ones that you want to fix.
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I utjecat će na normalne sklopove, kao i na one abnormalne koje želite popraviti.
04:26
So again, we're sent back to the idea
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Dakle, opet smo se vratili na ideju
04:28
of ultra-precise control.
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ultraprecizne kontrole.
04:30
Could we dial-in information precisely where we want it to go?
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Možemo li usmjeriti informaciju točno tamo kamo želimo da ode?
04:34
So when I started in neuroscience 11 years ago,
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I tako, kada sam se počeo baviti neuroznanošću prije 11 godina,
04:38
I had trained as an electrical engineer and a physicist,
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bio sam školovan kao električni inžinjer i fizičar
04:41
and the first thing I thought about was,
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i prva stvar na koju sam pomislio jest da,
04:43
if these neurons are electrical devices,
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ako su ovi neuroni električne naprave,
04:45
all we need to do is to find some way
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sve što moramo napraviti jest naći neki način
04:47
of driving those electrical changes at a distance.
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da provedemo te električne promjene s daljine.
04:49
If we could turn on the electricity in one cell,
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Kad bismo mogli izazvati elektricitet u jednoj stanici,
04:51
but not its neighbors,
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ali ne u njezinim susjedama,
04:53
that would give us the tool we need to activate and shut down these different cells,
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to bi nam dalo alat kojim bismo mogli aktivirati i ugasiti te različite stanice,
04:56
figure out what they do and how they contribute
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otkriti što one rade i kako doprinose
04:58
to the networks in which they're embedded.
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mrežama u koje su uključene.
05:00
And also it would allow us to have the ultra-precise control we need
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To bi nam također omogućilo da imamo ultrapreciznu kontrolu koju trebamo
05:02
in order to fix the circuit computations
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kako bismo popravili rezultate sklopova
05:05
that have gone awry.
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koji su pošli po krivu.
05:07
Now how are we going to do that?
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Kako ćemo to učiniti?
05:09
Well there are many molecules that exist in nature,
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Pa, u prirodi postoji mnogo molekula
05:11
which are able to convert light into electricity.
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koje su sposobne pretvoriti svjetlost u elektricitet.
05:14
You can think of them as little proteins
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Možete o njima razmišljati kao o malim proteinima
05:16
that are like solar cells.
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koji su kao solarne ćelije.
05:18
If we can install these molecules in neurons somehow,
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Kada bismo nekako mogli instalirati te molekule u neurone,
05:21
then these neurons would become electrically drivable with light.
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tada bi ti neuroni postali električno upravljivi svjetlom.
05:24
And their neighbors, which don't have the molecule, would not.
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A njihovi susjedi koji nemaju tu molekulu ne bi to bili.
05:27
There's one other magic trick you need to make this all happen,
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Postoji još jedan magični trik koji vam treba kako bi se sve to dogodilo,
05:29
and that's the ability to get light into the brain.
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a to je sposobnost uvođenja svjetla u mozak.
05:32
And to do that -- the brain doesn't feel pain -- you can put --
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Da biste to učinili -- mozak ne osjeća bol -- možete staviti --
05:35
taking advantage of all the effort
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koristeći prednosti svih napora
05:37
that's gone into the Internet and communications and so on --
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koji su uloženi u internet i komunikacije itd.--
05:39
optical fibers connected to lasers
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optička sredstva povezana laserima
05:41
that you can use to activate, in animal models for example,
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koja možete koristiti da aktivirate, u životinjskim primjerima npr.
05:43
in pre-clinical studies,
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u predkliničkim istraživanjima,
05:45
these neurons and to see what they do.
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te neurone i da vidite što oni rade.
05:47
So how do we do this?
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Pa kako ćemo to učiniti?
05:49
Around 2004,
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Otprilike 2004.,
05:51
in collaboration with Gerhard Nagel and Karl Deisseroth,
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u suradnji s Gerhard Nagelom i Karlom Deisserothom,
05:53
this vision came to fruition.
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ta je vizija donijela plodove.
05:55
There's a certain alga that swims in the wild,
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Postoji određena alga koja pliva u divljini
05:58
and it needs to navigate towards light
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i mora navigirati prema svjetlu,
06:00
in order to photosynthesize optimally.
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kako bi optimalno fotosintetizirala.
06:02
And it senses light with a little eye-spot,
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Ona osjeća svjetlo pomoću male oko-točke
06:04
which works not unlike how our eye works.
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koja funkcionira slično našem oku.
06:07
In its membrane, or its boundary,
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U njezinoj membrani (ili njezinoj granici)
06:09
it contains little proteins
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sadrži male proteine
06:12
that indeed can convert light into electricity.
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koji zaista pretvaraju svjetlost u elektricitet.
06:15
So these molecules are called channelrhodopsins.
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Te se molekule zovu channelrhodopsini.
06:18
And each of these proteins acts just like that solar cell that I told you about.
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Svaki se od tih proteina ponaša baš kao solarna ćelija o kojoj sam vam govorio.
06:21
When blue light hits it, it opens up a little hole
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Kada ju pogodi plavo svjetlo, ona otvori malu rupu
06:24
and allows charged particles to enter the eye-spot,
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i dozvoli nabijenim česticama da uđu u oko-točku.
06:26
and that allows this eye-spot to have an electrical signal
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To dopušta toj oko-točki da ima električni signal
06:28
just like a solar cell charging up a battery.
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baš kao solarna ćelija koja puni bateriju.
06:31
So what we need to do is to take these molecules
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Dakle, ono što trebamo napraviti jest uzeti te molekule
06:33
and somehow install them in neurons.
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i nekako ih instalirati u neurone.
06:35
And because it's a protein,
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Budući da je to protein,
06:37
it's encoded for in the DNA of this organism.
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kodiran je za DNK svog organizma.
06:40
So all we've got to do is take that DNA,
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Dakle, sve što trebamo napraviti jest uzeti taj DNK,
06:42
put it into a gene therapy vector, like a virus,
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staviti ga u okvir genske terapije kao virus
06:45
and put it into neurons.
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i postaviti ga u neurone.
06:48
So it turned out that this was a very productive time in gene therapy,
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Ispalo je da je to bilo veoma produktivno vrijeme u genskoj terapiji
06:51
and lots of viruses were coming along.
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pa se pojavljivalo mnogo virusa
06:53
So this turned out to be very simple to do.
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te se ispostavilo da je to veoma jednostavno napraviti.
06:55
And early in the morning one day in the summer of 2004,
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Rano ujutro jednog ljetnog dana 2004.
06:58
we gave it a try, and it worked on the first try.
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pokušali smo i upalilo je iz prvog pokušaja.
07:00
You take this DNA and you put it into a neuron.
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Uzmete taj DNK i stavite ga u neuron.
07:03
The neuron uses its natural protein-making machinery
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Neuron koristi svoj prirodni protein, tvoreći mašineriju
07:06
to fabricate these little light-sensitive proteins
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za proizvodnju tih malih proteina osjetljivih na svjetlost
07:08
and install them all over the cell,
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i njihovo instaliranje po cijeloj stanici
07:10
like putting solar panels on a roof,
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poput postavljanja solarnih panela na krovu.
07:12
and the next thing you know,
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I u sljedećem trenutku
07:14
you have a neuron which can be activated with light.
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imate neuron koji može biti aktiviran pomoću svjetla.
07:16
So this is very powerful.
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Dakle, to je veoma moćno.
07:18
One of the tricks you have to do
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Jedan od trikova koje morate napraviti
07:20
is to figure out how to deliver these genes to the cells that you want
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jest shvatiti kako dostaviti te gene u one stanice koje želite,
07:22
and not all the other neighbors.
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a ne u ostale, susjedne stanice.
07:24
And you can do that; you can tweak the viruses
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I to možete napraviti; možete oblikovati viruse
07:26
so they hit just some cells and not others.
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da pogode samo one određene stanice.
07:28
And there's other genetic tricks you can play
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Postoje i drugi genetički trikovi koje možete iskoristiti
07:30
in order to get light-activated cells.
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kako biste dobili stanice koje se aktiviraju svjetlom.
07:33
This field has now come to be known as optogenetics.
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To je polje postalo poznato kao optogenetika.
07:37
And just as one example of the kind of thing you can do,
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I kao samo jedan primjer onoga što možete napraviti,
07:39
you can take a complex network,
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možete uzeti kompleksnu mrežu,
07:41
use one of these viruses to deliver the gene
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iskoristiti jedan od ovih virusa da dostave gene
07:43
just to one kind of cell in this dense network.
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određenoj vrsti stanica u ovoj gustoj mreži.
07:46
And then when you shine light on the entire network,
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I tada, kada osvjetlite cijelu mrežu,
07:48
just that cell type will be activated.
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aktivirat će se samo taj tip stanica.
07:50
So for example, lets sort of consider that basket cell I told you about earlier --
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Pa na primjer, hajdemo uzeti u obzir onu košarastu stanicu o kojoj sam vam govorio ranije --
07:53
the one that's atrophied in schizophrenia
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onu koja je zakržljala u slučaju šizofrenije
07:55
and the one that is inhibitory.
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i koja je inhibicijska.
07:57
If we can deliver that gene to these cells --
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Ako možete dostaviti taj gen u te stanice --
07:59
and they're not going to be altered by the expression of the gene, of course --
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one neće biti izmijenjene u genetskom smislu, naravno --
08:02
and then flash blue light over the entire brain network,
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i tada bljesnete plavim svjetlom preko cijele mreže mozga,
08:05
just these cells are going to be driven.
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samo će te stanice biti pokrenute.
08:07
And when the light turns off, these cells go back to normal,
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Kada se svjetlo ugasi, stanice se vrate u normalno stanje;
08:09
so they don't seem to be averse against that.
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dakle, čini se da se one ne protive tome.
08:12
Not only can you use this to study what these cells do,
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Ne samo da možete to iskoristiti kako biste proučavali što te stanice mogu
08:14
what their power is in computing in the brain,
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i koja je njihova moć u računanju mozga
08:16
but you can also use this to try to figure out --
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već i to možete iskoristiti kako biste shvatili --
08:18
well maybe we could jazz up the activity of these cells,
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pa možda biste mogli oživjeti aktivnost tih stanica
08:20
if indeed they're atrophied.
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ako one zaista jesu atrofirane.
08:22
Now I want to tell you a couple of short stories
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Sada vam želim ispričati nekoliko kratkih priča
08:24
about how we're using this,
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o tome kako to koristimo
08:26
both at the scientific, clinical and pre-clinical levels.
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i na znanstvenim, kliničkim i predkliničkim razinama.
08:29
One of the questions we've confronted
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Jedno od pitanja s kojima smo suočeni jest:
08:31
is, what are the signals in the brain that mediate the sensation of reward?
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„Koji signali u mozgu posreduju pri osjećaju nagrađenosti?“
08:34
Because if you could find those,
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Jer, kada bismo ih mogli pronaći,
08:36
those would be some of the signals that could drive learning.
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oni bi mogli biti neki od signala koji bi mogli upravljati učenjem.
08:38
The brain will do more of whatever got that reward.
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Mozak bi radio više onog što dovodi do te nagrade.
08:40
And also these are signals that go awry in disorders such as addiction.
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Također, postoje signali koji se iskrive u poremećajima poput ovisnosti.
08:43
So if we could figure out what cells they are,
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Pa, kada bismo mogli shvatiti koje su to stanice,
08:45
we could maybe find new targets
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možda bismo mogli pronaći nove mete
08:47
for which drugs could be designed or screened against,
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za koje bi lijekovi mogli biti dizajnirani ili ograđeni od njih
08:49
or maybe places where electrodes could be put in
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ili možda mjesta gdje bi elektrode mogle biti postavljene
08:51
for people who have very severe disability.
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za ljude koji imaju veoma ozbiljan invaliditet.
08:54
So to do that, we came up with a very simple paradigm
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Kako bismo to napravili, smislili smo veoma jednostavnu paradigmu
08:56
in collaboration with the Fiorella group,
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u suradnji s Fiorella grupom,
08:58
where one side of this little box,
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gdje jedna strana ove male kutije,
09:00
if the animal goes there, the animal gets a pulse of light
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ako životinja ode tamo, životinja dobije puls svjetla,
09:02
in order to make different cells in the brain sensitive to light.
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kako bi se određene stanice u mozgu učinile osjetljivima na svjetlo.
09:04
So if these cells can mediate reward,
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Ako te stanice mogu posredovati nagrađivanjem,
09:06
the animal should go there more and more.
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životinja bi trebala tamo odlaziti sve više i više.
09:08
And so that's what happens.
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I to je ono što se događa.
09:10
This animal's going to go to the right-hand side and poke his nose there,
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Ova će životinja otići u desnu stranu i dotaknuti svoj nos tamo;
09:12
and he gets a flash of blue light every time he does that.
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ona dobije bljesak plavog svjetla svaki put kada to napravi.
09:14
And he'll do that hundreds and hundreds of times.
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I učinit će to stotinama i stotinama puta.
09:16
These are the dopamine neurons,
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To su neuroni dopamina,
09:18
which some of you may have heard about, in some of the pleasure centers in the brain.
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o kojima ste možda nešto čuli slušajući o centrima za užitak koji se nalaze u mozgu.
09:20
Now we've shown that a brief activation of these
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Sada smo pokazali da je njihova kratka aktivacija
09:22
is enough, indeed, to drive learning.
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zaista dovoljna da stimulira učenje.
09:24
Now we can generalize the idea.
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Sada možemo tu ideju generalizirati.
09:26
Instead of one point in the brain,
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Umjesto jedne točke u mozgu,
09:28
we can devise devices that span the brain,
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možemo izumiti naprave koje obuhvaćaju cijeli mozak,
09:30
that can deliver light into three-dimensional patterns --
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koje mogu provesti svjetlo u trodimenzionalnim modelima --
09:32
arrays of optical fibers,
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mnoštvo optičkih vlakana,
09:34
each coupled to its own independent miniature light source.
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svaki sparen u vlastiti, minijaturni svjetlosni izvor.
09:36
And then we can try to do things in vivo
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I tada možemo probati učiniti uživo stvari
09:38
that have only been done to-date in a dish --
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koje su dosad bile rađene samo u posudama --
09:41
like high-throughput screening throughout the entire brain
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poput visokopropusnog skeniranja cijelog mozga
09:43
for the signals that can cause certain things to happen.
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za signale koji mogu uzrokovati određene stvari.
09:45
Or that could be good clinical targets
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Ili mogu biti dobre kliničke mete
09:47
for treating brain disorders.
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za liječenje moždanih poremećaja.
09:49
And one story I want to tell you about
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Jedna priča koju vam želim ispričati
09:51
is how can we find targets for treating post-traumatic stress disorder --
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je o tome kako pronalazimo mete za liječenje posttraumatskog stresnog poremećaja --
09:54
a form of uncontrolled anxiety and fear.
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oblika nekontrolirane anksioznosti i straha.
09:57
And one of the things that we did
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Jedna od stvari koju smo napravili
09:59
was to adopt a very classical model of fear.
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jest da smo prilagodili klasičan model straha.
10:02
This goes back to the Pavlovian days.
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Ovo odlazi natrag u doba Ivana Pavlova.
10:05
It's called Pavlovian fear conditioning --
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Zove se Pavlovo uvjetovanje strahom --
10:07
where a tone ends with a brief shock.
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gdje ton završava kratkim šokom.
10:09
The shock isn't painful, but it's a little annoying.
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Šok nije bolan, ali je pomalo iritantan.
10:11
And over time -- in this case, a mouse,
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I nakon nekog vremena -- u ovom slučaju miš,
10:13
which is a good animal model, commonly used in such experiments --
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koji je dobra životinja za model, često korištena u takvim eksperimentima --
10:15
the animal learns to fear the tone.
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životinja se nauči bojati tona.
10:17
The animal will react by freezing,
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Životinja će reagirati zamrzavanjem,
10:19
sort of like a deer in the headlights.
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pomalo kao jelen ispred prednjih svjetala.
10:21
Now the question is, what targets in the brain can we find
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Pitanje je koje mete u mozgu možemo naći,
10:24
that allow us to overcome this fear?
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a da će nam dopustiti da nadvladamo ovaj strah?
10:26
So what we do is we play that tone again
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Ono što činimo jest puštanje toga tona ponovno,
10:28
after it's been associated with fear.
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nakon što je bio povezan sa strahom.
10:30
But we activate targets in the brain, different ones,
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Ali aktiviramo mete u mozgu, neke druge,
10:32
using that optical fiber array I told you about in the previous slide,
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koristeći mnoštvo optičkih vlakana o kojima sam vam govorio na prošlom slajdu,
10:35
in order to try and figure out which targets
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kako bismo pokušali shvatiti koje mete u mozgu
10:37
can cause the brain to overcome that memory of fear.
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mogu uzrokovati nadvladavanje tog sjećanja straha.
10:40
And so this brief video
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Tako vam ovaj kratak video
10:42
shows you one of these targets that we're working on now.
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pokazuje jednu od tih meta na kojima trenutno radimo.
10:44
This is an area in the prefrontal cortex,
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Ovo je područje u prefrontalnom korteksu,
10:46
a region where we can use cognition to try to overcome aversive emotional states.
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u regiji gdje saznanja možemo iskoristiti, kako bismo pokušali premostiti neželjena emotivna stanja.
10:49
And the animal's going to hear a tone -- and a flash of light occurred there.
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Životinja će čuti ton -- i bljesak svjetla se ondje dogodi.
10:51
There's no audio on this, but you can see the animal's freezing.
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Nema zvuka na ovome, ali možete vidjeti životinju kako se zaustavlja.
10:53
This tone used to mean bad news.
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Ovaj ton značio je prije loše vijesti.
10:55
And there's a little clock in the lower left-hand corner,
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Ondje je mali sat u donjem lijevom kutu
10:57
so you can see the animal is about two minutes into this.
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pa možete vidjeti da je životinja otprilike dvije minute u tome.
11:00
And now this next clip
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Sada je ova snimka
11:02
is just eight minutes later.
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samo osam minuta kasnije.
11:04
And the same tone is going to play, and the light is going to flash again.
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Isti ton bit će pušten i svjetlo će opet bljesnuti.
11:07
Okay, there it goes. Right now.
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Ok, evo ga. Upravo sada.
11:10
And now you can see, just 10 minutes into the experiment,
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I sada možete vidjeti, u samo deset minuta eksperimenta,
11:13
that we've equipped the brain by photoactivating this area
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da smo opremili mozak aktivirajući ovo područje svjetlom,
11:16
to overcome the expression
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kako bismo premostili ovo sjećanje
11:18
of this fear memory.
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na osjećaj straha.
11:20
Now over the last couple of years, we've gone back to the tree of life
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Tijekom zadnjih nekoliko godina vratili smo se stablu života
11:23
because we wanted to find ways to turn circuits in the brain off.
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jer smo željeli pronaći načine za isključivanje sklopova u mozgu.
11:26
If we could do that, this could be extremely powerful.
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Kad bismo to mogli, bilo bi to veoma moćno.
11:29
If you can delete cells just for a few milliseconds or seconds,
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Kad bismo mogli poništiti stanice samo na milisekundu ili sekunde,
11:32
you can figure out what necessary role they play
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mogli bismo shvatiti kakvu nužnu ulogu one igraju
11:34
in the circuits in which they're embedded.
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u sklopovima u koje su uključene.
11:36
And we've now surveyed organisms from all over the tree of life --
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I sad smo preispitali organizme sa svih razina stabla života --
11:38
every kingdom of life except for animals, we see slightly differently.
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svako carstvo života, osim životinja, vidimo malo drugačije.
11:41
And we found all sorts of molecules, they're called halorhodopsins or archaerhodopsins,
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Našli smo razne vrste molekula koje se zovu halorodopsini ili arhearodopsini,
11:44
that respond to green and yellow light.
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a koje reagiraju na zeleno i žuto svjetlo.
11:46
And they do the opposite thing of the molecule I told you about before
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One čine suprotnu stvar od molekule s aktivatorom plavog svjetla
11:48
with the blue light activator channelrhodopsin.
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channelrodopsinom, o kojoj sam vam pričao ranije.
11:52
Let's give an example of where we think this is going to go.
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Hajdemo dati primjer za ono što mislimo kamo će sve ovo otići.
11:55
Consider, for example, a condition like epilepsy,
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Razmotrite, na primjer, stanje poput epilepsije,
11:58
where the brain is overactive.
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gdje je mozak pretjerano aktivan.
12:00
Now if drugs fail in epileptic treatment,
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Ako lijekovi zakažu u tretiranju epilepsije,
12:02
one of the strategies is to remove part of the brain.
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jedna je od strategija da se ukloni dio mozga.
12:04
But that's obviously irreversible, and there could be side effects.
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Ali to je očito nepovratno i moguće su neželjene posljedice.
12:06
What if we could just turn off that brain for a brief amount of time,
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Što ako bismo mogli jednostavno isključiti taj mozak na kratko vrijeme,
12:09
until the seizure dies away,
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dok napad ne prođe,
12:12
and cause the brain to be restored to its initial state --
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i vratiti mozak u početno stanje --
12:15
sort of like a dynamical system that's being coaxed down into a stable state.
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pomalo kao dinamični sistem koji je primoran natrag u stabilno stanje.
12:18
So this animation just tries to explain this concept
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Dakle, ta animacija samo pokušava objasniti taj koncept
12:21
where we made these cells sensitive to being turned off with light,
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u kojem smo stanice učinili osjetljivima na gašenje svjetlom
12:23
and we beam light in,
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i tada usmjerili svjetlo unutra
12:25
and just for the time it takes to shut down a seizure,
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samo za vrijeme potrebno da se napad zaustavi;
12:27
we're hoping to be able to turn it off.
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nadamo se da ćemo ga moći ugasiti.
12:29
And so we don't have data to show you on this front,
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Nemamo podatke za pokazati vam u vezi toga,
12:31
but we're very excited about this.
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ali smo jako uzbuđeni zbog toga.
12:33
Now I want to close on one story,
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Sada želim završiti s jednom pričom,
12:35
which we think is another possibility --
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za koju mislimo da je druga mogućnost --
12:37
which is that maybe these molecules, if you can do ultra-precise control,
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a to je da možda te molekule, ako možete koristiti preciznu kontrolu,
12:39
can be used in the brain itself
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mogu biti korištene u samom mozgu,
12:41
to make a new kind of prosthetic, an optical prosthetic.
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kako bi napravile novu vrstu prostetike, optičku prostetiku.
12:44
I already told you that electrical stimulators are not uncommon.
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Već sam vam rekao da električni stimulatori nisu neobični.
12:47
Seventy-five thousand people have Parkinson's deep-brain stimulators implanted.
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Sedamdeset pet tisuća ljudi ima ugrađene stimulatore duboko u mozgu za Parkinsonovu bolest.
12:50
Maybe 100,000 people have Cochlear implants,
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Možda 100.000 ljudi ima kohlearne implantante
12:52
which allow them to hear.
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koji im omogućuju da čuju.
12:54
There's another thing, which is you've got to get these genes into cells.
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I još jedna stvar, a to je da morate nekako dopremiti te gene u stanice.
12:57
And new hope in gene therapy has been developed
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Nova nada u genskoj terapiji bila je razvijena
13:00
because viruses like the adeno-associated virus,
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zbog virusa poput adenovirusa,
13:02
which probably most of us around this room have,
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koji vjerojatno ima većina nas u ovoj prostoriji,
13:04
and it doesn't have any symptoms,
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a za koji ne postoje nikakvi simptomi
13:06
which have been used in hundreds of patients
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koji su korišteni u stotinama pacijenata,
13:08
to deliver genes into the brain or the body.
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kako bi se geni izručili u mozak ili tijelo.
13:10
And so far, there have not been serious adverse events
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Dosada nije bilo ozbiljnijih štetnih događaja
13:12
associated with the virus.
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povezanih s virusom.
13:14
There's one last elephant in the room, the proteins themselves,
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Postoji još jedan slon u prostoriji, sami proteini,
13:17
which come from algae and bacteria and fungi,
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koji dolaze od algi, bakterija, gljiva
13:19
and all over the tree of life.
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i drugih vrsta živih bića.
13:21
Most of us don't have fungi or algae in our brains,
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Većina nas nema gljiva ili algi u svom mozgu,
13:23
so what is our brain going to do if we put that in?
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dakle, što će naš mozak učiniti ako to unesemo unutra?
13:25
Are the cells going to tolerate it? Will the immune system react?
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Hoće li stanice to tolerirati? Hoće li reagirati imunološki sustav?
13:27
In its early days -- these have not been done on humans yet --
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U ranim danima -- i ovi nisu bili provedeni na ljudima još uvijek --
13:29
but we're working on a variety of studies
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ali radili smo na mnogo različitih studija
13:31
to try and examine this,
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kako bismo to ispitali.
13:33
and so far we haven't seen overt reactions of any severity
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Dosad nismo vidjeli očite reakcije bilo kakve jačine
13:36
to these molecules
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na te molekule
13:38
or to the illumination of the brain with light.
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ili osvjetljenje mozga svjetlom.
13:41
So it's early days, to be upfront, but we're excited about it.
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Dakle, to su rani stadiji, da budemo iskreni, ali veoma smo uzbuđeni zbog toga.
13:44
I wanted to close with one story,
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Želio sam završiti s jednom pričom,
13:46
which we think could potentially
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za koju smatramo da bi potencijalno
13:48
be a clinical application.
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mogla biti klinička aplikacija.
13:50
Now there are many forms of blindness
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Postoje mnogi oblici sljepoće
13:52
where the photoreceptors,
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gdje fotoreceptori,
13:54
our light sensors that are in the back of our eye, are gone.
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naši svjetlosni senzori koji su u stražnjem dijelu oka, ne funkcioniraju.
13:57
And the retina, of course, is a complex structure.
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I mrežnica je, dakako, kompleksna struktura.
13:59
Now let's zoom in on it here, so we can see it in more detail.
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Hajdemo ju ovdje zumirati, kako bismo ju detaljnije vidjeli.
14:01
The photoreceptor cells are shown here at the top,
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Stanice fotoreceptora pokazane su na vrhu
14:04
and then the signals that are detected by the photoreceptors
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i tada signali koji su detektirani fotoreceptorima
14:06
are transformed by various computations
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bivaju transformirani raznim komputacijama,
14:08
until finally that layer of cells at the bottom, the ganglion cells,
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dok napokon taj sloj stanica na dnu, stanice ganglija,
14:11
relay the information to the brain,
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ne prenesu informaciju mozgu,
14:13
where we see that as perception.
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gdje mi to vidimo kao percepciju.
14:15
In many forms of blindness, like retinitis pigmentosa,
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U mnogim oblicima sljepoće, poput retinitis pigmentoze
14:18
or macular degeneration,
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ili degeneracije makule,
14:20
the photoreceptor cells have atrophied or been destroyed.
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fotoreceptori su zakržljali ili su uništeni.
14:23
Now how could you repair this?
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Kako bi se to moglo popraviti?
14:25
It's not even clear that a drug could cause this to be restored,
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Čak nije ni jasno bi li se lijek mogao koristiti da se to vrati
14:28
because there's nothing for the drug to bind to.
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jer ne postoji ništa za što bi se lijek vezao.
14:30
On the other hand, light can still get into the eye.
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S druge strane, svjetlost još uvijek može ući u oko.
14:32
The eye is still transparent and you can get light in.
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Oko je još uvijek prozirno i u njega možete uvesti svjetlo.
14:35
So what if we could just take these channelrhodopsins and other molecules
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Dakle, što ako bismo mogli jednostavno uzeti te channelrodopsine i druge molekule
14:38
and install them on some of these other spare cells
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i postaviti ih na neke od tih preostalih, rezervnih stanica
14:40
and convert them into little cameras.
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i pretvoriti ih u male kamere?
14:42
And because there's so many of these cells in the eye,
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Zbog postojanja mnoštva tih stanica u oku,
14:44
potentially, they could be very high-resolution cameras.
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potencijalno, to bi mogle biti visokorezolucijske kamere.
14:47
So this is some work that we're doing.
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Ovo je nešto od posla kojim smo se bavili.
14:49
It's being led by one of our collaborators,
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Vodi ga jedan od naših suradnika,
14:51
Alan Horsager at USC,
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Alan Horsager s USC-a,
14:53
and being sought to be commercialized by a start-up company Eos Neuroscience,
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a nova tvrtka Eos Neuroznanost, osnovana od strane
14:56
which is funded by the NIH.
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NIH-a (Nacionalnih instituta za zdravlje) ga traži za komercijalizaciju.
14:58
And what you see here is a mouse trying to solve a maze.
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Ovdje vidite miša koji pokušava proći labirintom.
15:00
It's a six-arm maze. And there's a bit of water in the maze
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To je labirint sa šest rukavaca. Tamo je malo vode u labirintu,
15:02
to motivate the mouse to move, or he'll just sit there.
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kako bi se miša motiviralo da se kreće, inače će samo sjediti ondje.
15:04
And the goal, of course, of this maze
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Cilj ovog labirinta jest, naravno,
15:06
is to get out of the water and go to a little platform
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izaći iz vode i otići na malu platformu
15:08
that's under the lit top port.
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koja je ispod osvjetljenog ulaza.
15:10
Now mice are smart, so this mouse solves the maze eventually,
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Miševi su pametni pa ovaj miš na kraju rješava labirint,
15:13
but he does a brute-force search.
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ali ga pretražuje grubom silom.
15:15
He's swimming down every avenue until he finally gets to the platform.
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On pliva svakim prolazom dok na kraju napokon ne dođe do platforme.
15:18
So he's not using vision to do it.
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Ne koristi se vidom.
15:20
These different mice are different mutations
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Ovi različiti miševi predstavljaju razne mutacije
15:22
that recapitulate different kinds of blindness that affect humans.
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koje oslikavaju različite vrste sljepoće koje pogađaju ljude.
15:25
And so we're being careful in trying to look at these different models
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Zato oprezno pregledavamo te različite modele,
15:28
so we come up with a generalized approach.
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kako bismo došli do općeg pristupa.
15:30
So how are we going to solve this?
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Dakle, kako ćemo ovo riješiti?
15:32
We're going to do exactly what we outlined in the previous slide.
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Učinit ćemo upravo ono što smo naznačili na posljednjem slajdu.
15:34
We're going to take these blue light photosensors
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Uzet ćemo te fotosenzore plavog svjetla
15:36
and install them on a layer of cells
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i postaviti ih na sloj stanica
15:38
in the middle of the retina in the back of the eye
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na sredini mrežnice u stražnjem dijelu oka
15:41
and convert them into a camera --
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i pretvorit ćemo ih u kameru.
15:43
just like installing solar cells all over those neurons
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Baš poput instaliranja solarnih ćelija po tim neuronima
15:45
to make them light sensitive.
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kako bismo ih učinili osjetljivima na svjetlost.
15:47
Light is converted to electricity on them.
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Na njima je svjetlost pretvorena u elektricitet.
15:49
So this mouse was blind a couple weeks before this experiment
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Dakle, ovaj je miš bio slijep nekoliko tjedana prije pokusa
15:52
and received one dose of this photosensitive molecule in a virus.
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i primio je jednu dozu tih molekula osjetljivih na svjetlo u virusu.
15:55
And now you can see, the animal can indeed avoid walls
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Sada možete vidjeti: životinja zaista može izbjegavati zidove
15:57
and go to this little platform
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i otići na tu malu platformu
15:59
and make cognitive use of its eyes again.
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i ponovno svjesno koristiti svoje oči.
16:02
And to point out the power of this:
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Još jedan plus u tome:
16:04
these animals are able to get to that platform
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ove životinje mogu doći do platforme
16:06
just as fast as animals that have seen their entire lives.
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jednako brzo kao životinje koje vide cijeli život.
16:08
So this pre-clinical study, I think,
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Dakle, ovo je predklinička nauka. Mislim,
16:10
bodes hope for the kinds of things
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mnogi se nadaju onim stvarima
16:12
we're hoping to do in the future.
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koje ćemo jedanput, nadamo se, i mi moći činiti.
16:14
To close, I want to point out that we're also exploring
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Da završim, želio bih istaknuti da također istražujemo
16:17
new business models for this new field of neurotechnology.
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nove poslovne modele za ovo novo polje neurotehnologije.
16:19
We're developing these tools,
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Razvijamo ova oruđa,
16:21
but we share them freely with hundreds of groups all over the world,
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ali dijelimo ih besplatno sa stotinama grupa diljem svijeta,
16:23
so people can study and try to treat different disorders.
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kako bi ljudi mogli proučavati i liječiti različite poremećaje.
16:25
And our hope is that, by figuring out brain circuits
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Nadamo se da ćemo, shvaćajući moždane sklopove
16:28
at a level of abstraction that lets us repair them and engineer them,
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na razini apstrakcije koja nam dozvoljava da ih popravljamo i njima upravljamo,
16:31
we can take some of these intractable disorders that I told you about earlier,
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moći uzeti neke od neukrotivih poremećaja, o kojima sam vam ranije govorio,
16:34
practically none of which are cured,
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od kojih praktički nijedan nije izliječen,
16:36
and in the 21st century make them history.
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i u 21. stoljeću ih učiniti prošlošću.
16:38
Thank you.
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Hvala vam.
16:40
(Applause)
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(Pljesak)
16:53
Juan Enriquez: So some of the stuff is a little dense.
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Juan Enriquez: Dakle, neke od ovih stvari malo su guste.
16:56
(Laughter)
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(Smijeh)
16:58
But the implications
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Ali implikacije
17:00
of being able to control seizures or epilepsy
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mogućnosti da se kontroliraju napadi epilepsije
17:03
with light instead of drugs,
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sa svjetlom, umjesto s lijekovima,
17:05
and being able to target those specifically
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i da se posebno ciljaju
17:08
is a first step.
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jest prvi korak.
17:10
The second thing that I think I heard you say
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Sljedeći, mislim da sam vas tako čuo,
17:12
is you can now control the brain in two colors,
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jest taj da sada možete kontrolirati mozak u dvjema bojama.
17:15
like an on/off switch.
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Poput prekidača upali-ugasi.
17:17
Ed Boyden: That's right.
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Ed Boyden: Tako je.
17:19
JE: Which makes every impulse going through the brain a binary code.
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JE: Što svaki impuls koji prolazi mozgom čini binarnim kodom.
17:22
EB: Right, yeah.
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EB: Tako je, da.
17:24
So with blue light, we can drive information, and it's in the form of a one.
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Dakle, plavim svjetlom možemo provesti informacije i to je u obliku jedinice.
17:27
And by turning things off, it's more or less a zero.
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Isključujući stvari, to je više-manje nula.
17:29
So our hope is to eventually build brain coprocessors
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Dakle, nadamo se da ćemo na kraju izgraditi koprocesore
17:31
that work with the brain
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u mozgu koji s njim surađuju,
17:33
so we can augment functions in people with disabilities.
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kako bismo mogli povećati funkcije kod ljudi s invaliditetom.
17:36
JE: And in theory, that means that,
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JE: A u teoriji to znači da,
17:38
as a mouse feels, smells,
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dok miš osjeća, miriše,
17:40
hears, touches,
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sluša, dodiruje,
17:42
you can model it out as a string of ones and zeros.
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možete modulirati kao niz jedinica i nula.
17:45
EB: Sure, yeah. We're hoping to use this as a way of testing
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EB: Svakako, da. Nadamo se da ćemo to koristiti kao način testiranja
17:47
what neural codes can drive certain behaviors
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koji neutralni kodovi mogu pokrenuti određena ponašanja,
17:49
and certain thoughts and certain feelings,
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određene misli i određene osjećaje,
17:51
and use that to understand more about the brain.
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i iskoristiti to kako bismo bolje razumjeli mozak.
17:54
JE: Does that mean that some day you could download memories
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JE: Znači li to da ćemo jednog dana moći „skinuti“ sjećanja
17:57
and maybe upload them?
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i možda ih postavljati?
17:59
EB: Well that's something we're starting to work on very hard.
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EB. Pa to je nešto na čemu počinjemo veoma marljivo raditi.
18:01
We're now working on some work
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Sada radimo na nečemu
18:03
where we're trying to tile the brain with recording elements too.
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gdje pokušavamo pokriti mozak također elementima snimača.
18:05
So we can record information and then drive information back in --
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Tako možemo snimiti informacije i tada ih opet provesti unutra --
18:08
sort of computing what the brain needs
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poput računanja onoga što mozak treba,
18:10
in order to augment its information processing.
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kako bismo poboljšali procesuiranje informacija.
18:12
JE: Well, that might change a couple things. Thank you. (EB: Thank you.)
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JE. Pa, to bi moglo promijeniti neke stvari. Hvala vam. (EB: Hvala vama.)
18:15
(Applause)
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(Pljesak)
ABOUT THE SPEAKER
Ed Boyden - NeuroengineerEd Boyden is a professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and the MIT McGovern Institute.
Why you should listen
Ed Boyden leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain. His group applies these tools in a systematic way in order to reveal ground truth scientific understandings of biological systems, which in turn reveal radical new approaches for curing diseases and repairing disabilities. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision, and optogenetic tools, which enable the activation and silencing of neural activity with light (TED Talk: A light switch for neurons). Boyden also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.
Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013) and the NIH Director's Pioneer Award (2013). He was also named to the World Economic Forum Young Scientist list (2013) and the Technology Review World's "Top 35 Innovators under Age 35" list (2006). His group has hosted hundreds of visitors to learn how to use new biotechnologies and spun out several companies to bring inventions out of his lab and into the world. Boyden received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents and articles, and he has given over 300 invited talks on his group's work.
Ed Boyden | Speaker | TED.com