TED2011
Ed Boyden: A light switch for neurons
Ed Bojden: Svetlosni okidač neurona
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Ed Bojden pokazuje kako, umečući gene za svetlosno osetljive proteine u moždane ćelije, može selektivno aktivisati ili deaktivisati specifične neurone s implantima od optičkih vlakana. S tom neprikosnovenom razinom kontrole, on je uspeo izlečiti miša od PTSP-a i određenih formi slepoće. Na horizontu: neuralna prostetika. Voditelj seanse Huan Enrikez vodi kratak Q&A nakon govora.
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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Razislite o svom danu jedan trenutak.
00:17
You woke up, felt fresh air on your face as you walked out the door,
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Probudili ste se. Osetili ste svež vazduh na licu izlazeći iz kuće,
00:20
encountered new colleagues and had great discussions,
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sreli ste nove kolege i imali sjajne razgovore,
00:22
and felt in awe when you found something new.
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i osetili strahopoštovanje kada ste otkrili nešto novo.
00:24
But I bet there's something you didn't think about today --
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Ali kladim se da postoji stvar na koju danas niste pomislili --
00:26
something so close to home
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nešto svima tako blisko
00:28
that you probably don't think about it very often at all.
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da verovatno o tome ne mislite uopšte.
00:30
And that's that all the sensations, feelings,
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A mislim na to da u svemu što zapazite, osetite,
00:32
decisions and actions
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odlučite i uradite
00:34
are mediated by the computer in your head
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posreduje kompjuter u vašoj glavi
00:36
called the brain.
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koji zovemo mozak.
00:38
Now the brain may not look like much from the outside --
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Znam da mozak ne izgleda bog zna kako spolja --
00:40
a couple pounds of pinkish-gray flesh,
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par kilograma ružičasto-sive mase,
00:42
amorphous --
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amorfne --
00:44
but the last hundred years of neuroscience
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ali poslednjih stotinjak godina neuronauke
00:46
have allowed us to zoom in on the brain,
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su nam omogućile da "zumiramo" mozak
00:48
and to see the intricacy of what lies within.
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i vidimo komplikovanost onoga što se nalazi unutra.
00:50
And they've told us that this brain
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Oni nam govore da je mozak
00:52
is an incredibly complicated circuit
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neverovatno komplikovano ispovezivan
00:54
made out of hundreds of billions of cells called neurons.
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sačinjen od stotina milijardi ćelija zvanih neuroni.
00:58
Now unlike a human-designed computer,
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Nasuprot kompjuteru koji su napravili ljudi,
01:01
where there's a fairly small number of different parts --
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koji čini relativno mali broj različitih delova --
01:03
we know how they work, because we humans designed them --
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za njih znamo kako rade jer smo ih mi, ljudi, dizajnirali --
01:06
the brain is made out of thousands of different kinds of cells,
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mozak se sastoji od hiljada različitih vrsta ćelija,
01:09
maybe tens of thousands.
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možda desetina hiljada.
01:11
They come in different shapes; they're made out of different molecules.
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Te ćelije su različitih oblika; čine ih različiti molekuli;
01:13
And they project and connect to different brain regions,
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i one projektuju i povezuju se sa različitim regijama mozga.
01:16
and they also change different ways in different disease states.
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One se i menjaju na različite načine u različitim stadijumima bolesti.
01:19
Let's make it concrete.
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Da konkretizujem.
01:21
There's a class of cells,
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Postoji klasa ćelija,
01:23
a fairly small cell, an inhibitory cell, that quiets its neighbors.
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prilično mala ćelija, inhibitorna ćelija, koja umiruje susedne.
01:26
It's one of the cells that seems to be atrophied in disorders like schizophrenia.
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Čini se da te ćelije atrofiraju u stanjima kao što je šizofrenija.
01:30
It's called the basket cell.
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Zovu je korpasta ćelija.
01:32
And this cell is one of the thousands of kinds of cell
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Ta ćelija je jedna od hiljada vrsta ćelija
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 otkrivaju svakoga dana.
01:38
As just a second example:
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Evo drugog primera:
01:40
these pyramidal cells, large cells,
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ove piramidalne ćelije, velike ćelije,
01:42
they can span a significant fraction of the brain.
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one se mogu prostirati značajnim delom mozga.
01:44
They're excitatory.
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One su pobuđujuće.
01:46
And these are some of the cells
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I to su samo neke od ćelija
01:48
that might be overactive in disorders such as epilepsy.
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koje bi mogle biti previše aktivne u poremećajima kao što je epilepsija.
01:51
Every one of these cells
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Svaka od ovih ćelija
01:53
is an incredible electrical device.
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je neverovatna električna naprava.
01:56
They receive input from thousands of upstream partners
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One primaju podatke od hiljada prethodećih partnera
01:58
and compute their own electrical outputs,
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i proračunavaju njihov sopstveni električni izlaz,
02:01
which then, if they pass a certain threshold,
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koji onda, ako pređu određeni prag,
02:03
will go to thousands of downstream partners.
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nastavlja ka hiljadama narednih partnera.
02:05
And this process, which takes just a millisecond or so,
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Taj proces, koji traje praktično samo milisekundu,
02:08
happens thousands of times a minute
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odvija se hiljadama puta u minuti
02:10
in every one of your 100 billion cells,
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u svakoj od vaših 100 milijardi ćelija,
02:12
as long as you live
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dok ste živi
02:14
and think and feel.
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i mislite i osećate.
02:17
So how are we going to figure out what this circuit does?
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I kako ćete da odgonetnete šta to kolo radi?
02:20
Ideally, we could go through the circuit
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U idealnoj varijanti, mogli bi da prođemo tim kolom
02:22
and turn these different kinds of cell on and off
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i tom prilikom da te raznorazne ćelije aktiviramo i deaktiviramo
02:25
and see whether we could figure out
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i vidimo da li tako možemo da zaključimo
02:27
which ones contribute to certain functions
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koje učestvuju u određenim funkcijama
02:29
and which ones go wrong in certain pathologies.
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a koje se kvare usled nekih patologija.
02:31
If we could activate cells, we could see what powers they can unleash,
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Ako bismo mogli da aktiviramo ćelije, mogli bi videti energiju koju one oslobađaju,
02:34
what they can initiate and sustain.
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šta mogu da iniciraju i podrže.
02:36
If we could turn them off,
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Ako bismo mogli da ih isključimo,
02:38
then we could try and figure out what they're necessary for.
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onda bi mogli da pokušamo da odgonetnemo za šta su neophodne.
02:40
And that's a story I'm going to tell you about today.
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E to je priča koju ću vam danas ispričati.
02:43
And honestly, where we've gone through over the last 11 years,
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Iskreno, kuda smo prošli u prethodnih 11 godina,
02:46
through an attempt to find ways
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pokušavajući da nađemo načine
02:48
of turning circuits and cells and parts and pathways of the brain
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da kola i ćelije i delove i putanje u mozgu
02:50
on and off,
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aktiviramo i deaktiviramo
02:52
both to understand the science
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i da bi razumeli nauku,
02:54
and also to confront some of the issues
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ali i da bi se suočili sa nekim pitanjima
02:57
that face us all as humans.
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koja se tiču svih nas, ljudskih bića.
03:00
Now before I tell you about the technology,
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Sada, pre priče o tehnologiji,
03:03
the bad news is that a significant fraction of us in this room,
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loša vest je da će značajan broj nas u ovoj prostoriji,
03:06
if we live long enough,
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ako poživimo dovoljno dugo,
03:08
will encounter, perhaps, a brain disorder.
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verovatno, doživeti neki moždani poremećaj.
03:10
Already, a billion people
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Već sada, milijarda ljudi
03:12
have had some kind of brain disorder
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pati od neke vrste moždanog poremećaja
03:14
that incapacitates them,
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koja ih onesposobljava.
03:16
and the numbers don't do it justice though.
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A brojevi nam nisu naklonjeni.
03:18
These disorders -- schizophrenia, Alzheimer's,
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Ti poremećaji -- šizofrenija, Alchajmer,
03:20
depression, addiction --
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depresija, zavisnosti --
03:22
they not only steal our time to live, they change who we are.
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ne samo da nam skraćuju životni vek, oni nas menjaju;
03:25
They take our identity and change our emotions
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oni nam oduzimaju identitet i menjaju naša osećanja --
03:27
and change who we are as people.
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i menjaju nas kao osobe.
03:30
Now in the 20th century,
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Sada, u 20. veku,
03:33
there was some hope that was generated
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postojala je nada koju je generisao
03:36
through the development of pharmaceuticals for treating brain disorders,
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razvoj farmaceutskih proizvoda za tretiranje moždanih poremećaja.
03:39
and while many drugs have been developed
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Dok su razvijani mnogi lekovi
03:42
that can alleviate symptoms of brain disorders,
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koji ublažavaju simptome moždanih poremećaja,
03:44
practically none of them can be considered to be cured.
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praktično nijedan od njih nije moga biti izlečen.
03:47
And part of that's because we're bathing the brain in the chemical.
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Deo razloga je što preplavljujemo mozak hemikalijama.
03:50
This elaborate circuit
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Ovo složeno kolo
03:52
made out of thousands of different kinds of cell
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sačinjeno od hiljada različitih vrsta ćelija
03:54
is being bathed in a substance.
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počinje da biva preplavljeno supstancama.
03:56
That's also why, perhaps, most of the drugs, and not all, on the market
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Možda je to razlog zašto većina lekova, ali ne svi, koji su na tržištu
03:58
can present some kind of serious side effect too.
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ima ozbiljne neželjene efekte.
04:01
Now some people have gotten some solace
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Neki ljudi nalaze utehu
04:04
from electrical stimulators that are implanted in the brain.
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od električnih stimulatora koji su im ugrađeni u mozak.
04:07
And for Parkinson's disease,
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Ili u slučaju Parkinsonove bolesti,
04:09
Cochlear implants,
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kohlearni implanti,
04:11
these have indeed been able
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koji su zaista uspeli
04:13
to bring some kind of remedy
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da donesu neku vrstu poboljšanja
04:15
to people with certain kinds of disorder.
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ljudima sa određenim vrstama poremećaja.
04:17
But electricity also will go in all directions --
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Ali elektricitet ide u svim pravcima --
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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što je, delom, i poreklo fraze.
04:23
And it also will affect normal circuits as well as the abnormal ones that you want to fix.
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A uticaće i na normalna kola baš kao i na abnormalna koja želite da popravite.
04:26
So again, we're sent back to the idea
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I tako smo se vratili ideji
04:28
of ultra-precise control.
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ultra precizne kontrole.
04:30
Could we dial-in information precisely where we want it to go?
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Možemo li poslati informaciju precizno tamo gde želimo da ona ode?
04:34
So when I started in neuroscience 11 years ago,
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I tako, kada sam ja počeo da se bavim neuronaukom pre 11 godina,
04:38
I had trained as an electrical engineer and a physicist,
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posedovao sam znanja električnog inženjera i fizičara,
04:41
and the first thing I thought about was,
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a prva stvar koju su me naučili je bila
04:43
if these neurons are electrical devices,
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da ako su neuroni električni sklopovi,
04:45
all we need to do is to find some way
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sve što treba da uradimo je da nađemo način
04:47
of driving those electrical changes at a distance.
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da izvedemo električne promene sa daljine.
04:49
If we could turn on the electricity in one cell,
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Ako bi mogli da izazovemo elekticitet u jednoj ćeliji,
04:51
but not its neighbors,
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ali ne i u susednoj,
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 koji nam treba da aktiviramo i deaktiviramo te različite ćelije,
04:56
figure out what they do and how they contribute
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da otkrijemo šta one rade i kako doprinose
04:58
to the networks in which they're embedded.
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mreži u koju su smeštene.
05:00
And also it would allow us to have the ultra-precise control we need
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To bi nam omogućilo i da imamo ultra precizne kontrole koje nam trebaju
05:02
in order to fix the circuit computations
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da bi mogli da popravimo rezultate kola
05:05
that have gone awry.
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koja su zastranila.
05:07
Now how are we going to do that?
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Kako ćemo to da uradimo?
05:09
Well there are many molecules that exist in nature,
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Pa, u prirodi postoje mnogi molekuli
05:11
which are able to convert light into electricity.
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koji su sposobni da pretvore svetlost u elektricitet.
05:14
You can think of them as little proteins
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Možete o njima misliti 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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Ako bi nekako mogli da instaliramo te molekule u neurone
05:21
then these neurons would become electrically drivable with light.
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onda bi ti neuroni postali elektro-upravljivi svetlom.
05:24
And their neighbors, which don't have the molecule, would not.
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A njihovi susedi, koji nemaju dodate molekule, ne bi 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 da bi se sve ovo desilo
05:29
and that's the ability to get light into the brain.
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a to je načičn da uvedete svetlost u mozak.
05:32
And to do that -- the brain doesn't feel pain -- you can put --
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Da bi to uradili -- mozak ne oseća bol -- možete ugraditi --
05:35
taking advantage of all the effort
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zahvaljujući svemu što je uloženo
05:37
that's gone into the Internet and communications and so on --
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u razvoj internet i komunikacije i slično --
05:39
optical fibers connected to lasers
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optička vlakna prikopčana na lasere
05:41
that you can use to activate, in animal models for example,
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koja možete koristiti za aktiviranje, na primer u životinjskim modelima,
05:43
in pre-clinical studies,
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u predkliničkim studijama,
05:45
these neurons and to see what they do.
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ovih neurona i tako videti šta rade.
05:47
So how do we do this?
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Pa kako ćemo to da izvedemo?
05:49
Around 2004,
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U 2004. godini,
05:51
in collaboration with Gerhard Nagel and Karl Deisseroth,
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u saradnji sa Gerhardom Najdželom i Karlom Deiserotom,
05:53
this vision came to fruition.
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ova vizija je dala plodove.
05:55
There's a certain alga that swims in the wild,
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Postoji alga koja obitava u divljini,
05:58
and it needs to navigate towards light
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i ona se kreće prema svetlu
06:00
in order to photosynthesize optimally.
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da bi optimalno obavljala fotosintezu.
06:02
And it senses light with a little eye-spot,
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Ona oseća svetlost malom tačkom-okom,
06:04
which works not unlike how our eye works.
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koja funkcioniše ne bitno različito od našeg oka.
06:07
In its membrane, or its boundary,
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U membrani, ili na njenoj 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 svetlost u elektricitet.
06:15
So these molecules are called channelrhodopsins.
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Ti molekuli se zovu channelrhodopsin-i
06:18
And each of these proteins acts just like that solar cell that I told you about.
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I svaki od tih proteina deluje kao solarna ćelija o kojoj sam vam pričao.
06:21
When blue light hits it, it opens up a little hole
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Kada je pogodi plavo svetlo, otvori se mala rupa
06:24
and allows charged particles to enter the eye-spot,
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i čestica sa nabojem uđe u tačku-oko.
06:26
and that allows this eye-spot to have an electrical signal
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Time tačka-oko dobija električni impuls
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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Znači, ono što treba da uradimo je da uzmemo te molekule
06:33
and somehow install them in neurons.
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i nekako ih instaliramo u neurone.
06:35
And because it's a protein,
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A pošto su to proteini,
06:37
it's encoded for in the DNA of this organism.
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kodirani su za DNK tih organizama.
06:40
So all we've got to do is take that DNA,
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Sve što treba da uradimo je da uzmemo tu DNK
06:42
put it into a gene therapy vector, like a virus,
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ubacimo je u okviru genske terapije, kao virus,
06:45
and put it into neurons.
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i ugradimo je u neuron.
06:48
So it turned out that this was a very productive time in gene therapy,
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Ispostavilo se da je ovo veoma produktivno vreme u smislu genske terapije,
06:51
and lots of viruses were coming along.
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i mnogi virusi su se pojavljivali.
06:53
So this turned out to be very simple to do.
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Tako je ovo postalo lako izvodivo.
06:55
And early in the morning one day in the summer of 2004,
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Ranim jutrom jednog dana u septembru 2004.
06:58
we gave it a try, and it worked on the first try.
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pokušali smo i proradilo je iz prve.
07:00
You take this DNA and you put it into a neuron.
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Uzmete ovu DNK i stavite je u neuron.
07:03
The neuron uses its natural protein-making machinery
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Neuroni su koristili prirodan proces za pravljenje proteina
07:06
to fabricate these little light-sensitive proteins
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da bi prizveli ove male fotoosetljive proteine
07:08
and install them all over the cell,
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i instalirali ih svuda po ćeliji,
07:10
like putting solar panels on a roof,
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kao što se postavljaju solarni paneli na krov.
07:12
and the next thing you know,
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I tek tako,
07:14
you have a neuron which can be activated with light.
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imate neuron koji može da se aktivira pomoću svetla.
07:16
So this is very powerful.
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To je tako moćno.
07:18
One of the tricks you have to do
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Jedna od stvari koje treba da uradite
07:20
is to figure out how to deliver these genes to the cells that you want
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je da odgonetnete kako da isporučite te gene u ćelije koje ste odredili
07:22
and not all the other neighbors.
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a ne u sve ćelije u okolini.
07:24
And you can do that; you can tweak the viruses
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I to može da se uradi; moguće je "oblikovati" viruse
07:26
so they hit just some cells and not others.
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tako da pogode samo određene ćelije a ne neke druge.
07:28
And there's other genetic tricks you can play
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A postoje i drugi genetičarski trikovi koje možete primeniti
07:30
in order to get light-activated cells.
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da bi dobili ćelije koje se aktiviraju svetlom.
07:33
This field has now come to be known as optogenetics.
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Ova oblast je sada poznata kao optogenetika.
07:37
And just as one example of the kind of thing you can do,
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Evo jedan primer onoga što možete da uradite,
07:39
you can take a complex network,
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možete uzeti kompleksnu mrežu i
07:41
use one of these viruses to deliver the gene
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upotrebiti neki od virusa da isporučite gen
07:43
just to one kind of cell in this dense network.
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samo jednoj vrsti ćelija u toj gustoj mreži.
07:46
And then when you shine light on the entire network,
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Kada obasjate svetlom celu mrežu
07:48
just that cell type will be activated.
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aktiviraće se samo odabrana vrsta ćelija.
07:50
So for example, lets sort of consider that basket cell I told you about earlier --
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Na primer, hajde da vidimo one korpaste ćelije o kojima sam ranije pričao --
07:53
the one that's atrophied in schizophrenia
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one koje atrofiraju u šizofreniji
07:55
and the one that is inhibitory.
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koje su inhibitorne.
07:57
If we can deliver that gene to these cells --
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Ako možemo da isporučimo odabrane gene tim ćelijama --
07:59
and they're not going to be altered by the expression of the gene, of course --
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naravno, to ih neće, u genetskom smislu, promeniti --
08:02
and then flash blue light over the entire brain network,
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i ako onda obasjamo plavom svetlošću kompletnu moždanu mrežu,
08:05
just these cells are going to be driven.
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samo će se odabrane ćelije pokrenuti.
08:07
And when the light turns off, these cells go back to normal,
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Kada ugasimo svetlo, te ćelije će se vratiti u normalu
08:09
so they don't seem to be averse against that.
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tako da nisu trajno izmenjene.
08:12
Not only can you use this to study what these cells do,
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Ne samo da ovo možete da koristite da bi studirali šta ove ćelije rade,
08:14
what their power is in computing in the brain,
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koji je njihov značaj u proračunima mozga,
08:16
but you can also use this to try to figure out --
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nego možete koristiti ovo da bi pokušali da odgonetnete --
08:18
well maybe we could jazz up the activity of these cells,
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možda bi mogli da oživimo aktivnosti ovih ćelija,
08:20
if indeed they're atrophied.
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ako one zaista atrofiraju.
08:22
Now I want to tell you a couple of short stories
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Sada bih želeo da vam ispričam nekoliko kratkih priča
08:24
about how we're using this,
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o tome kako koristimo ovo,
08:26
both at the scientific, clinical and pre-clinical levels.
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na naučnom, kliničkom i predkliničkom nivou.
08:29
One of the questions we've confronted
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Jedno od pitanja sa kojima smo se susreli
08:31
is, what are the signals in the brain that mediate the sensation of reward?
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je koji signali u mozgu posreduju osećaju nagrade?
08:34
Because if you could find those,
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Jer ako možemo da pronađemo njih,
08:36
those would be some of the signals that could drive learning.
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to bi bili neki od signala koji bi mogli da podstiču učenje.
08:38
The brain will do more of whatever got that reward.
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Mozak bi radio više onoga što se nagrađuje.
08:40
And also these are signals that go awry in disorders such as addiction.
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Ujedno, to su signali koji oslabe pri poremećajima kao što je zavisnost.
08:43
So if we could figure out what cells they are,
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Ako bi mogli da odgonetnemo koje su to ćelije,
08:45
we could maybe find new targets
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možda bi mogli da nađemo nove ciljeve
08:47
for which drugs could be designed or screened against,
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za koje bi mogli da napravimo lekove ili koje bi mogli da izolujemo,
08:49
or maybe places where electrodes could be put in
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ili možda mesta u koja bi mogli da uvedemo elektrode
08:51
for people who have very severe disability.
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ljudima koji pate od ozbiljnih invaliditeta.
08:54
So to do that, we came up with a very simple paradigm
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Da bi to uradili, smislili smo veoma jednostavan primer
08:56
in collaboration with the Fiorella group,
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u saradnji sa Fiorela grupom,
08:58
where one side of this little box,
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u kome na jednoj strani ove male kutije,
09:00
if the animal goes there, the animal gets a pulse of light
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ako životinja prođe tuda, životinja dobije bljesak svetla
09:02
in order to make different cells in the brain sensitive to light.
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da bi učinila druge ćelije mozga osetljive na svetlo.
09:04
So if these cells can mediate reward,
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Ako te ćelije posreduju pri nagradi,
09:06
the animal should go there more and more.
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životinja će sve više i više ići tuda.
09:08
And so that's what happens.
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I to se i desilo.
09:10
This animal's going to go to the right-hand side and poke his nose there,
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Ova životinja će ići ka desnoj strani i promoliće nos tamo,
09:12
and he gets a flash of blue light every time he does that.
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i dobiti bljesak plavog svetla svaki put kada to učini.
09:14
And he'll do that hundreds and hundreds of times.
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I ona će to učiniti stotine i stotine puta.
09:16
These are the dopamine neurons,
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Ovo 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 su neki od vas možda čuli, u nekim od centara za zadovoljstvno u mozgu.
09:20
Now we've shown that a brief activation of these
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Pokazali smo da je njihova kratka aktivacija
09:22
is enough, indeed, to drive learning.
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dovoljna, zaista, da bi podstakla učenje.
09:24
Now we can generalize the idea.
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Iz toga možemo da generalizujemo ideju.
09:26
Instead of one point in the brain,
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Umesto jedne tačke u mozgu,
09:28
we can devise devices that span the brain,
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možemo izmisliti napravu koja može obuhvatiti mozak,
09:30
that can deliver light into three-dimensional patterns --
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koja može dopremiti svetlo u trodimenzionalnom obliku --
09:32
arrays of optical fibers,
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nizovi optičkih vlakana,
09:34
each coupled to its own independent miniature light source.
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svaki uparen sa njegovim nezavisnim minijaturnim izvorom svetla.
09:36
And then we can try to do things in vivo
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I tada možemo da pokušamo stvari na živo
09:38
that have only been done to-date in a dish --
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koje su do sada rađene samo u posudama --
09:41
like high-throughput screening throughout the entire brain
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kao što je visoko-propusno nadgledanje kompletnog mozga
09:43
for the signals that can cause certain things to happen.
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zbog signala koji mogu prouzrokovati dešavanje određenih stvari.
09:45
Or that could be good clinical targets
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Ili bi mogli da budu dobre kliničke ciljane grupe
09:47
for treating brain disorders.
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za tretmane poremećaja mozga.
09:49
And one story I want to tell you about
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Evo još jedne priče koju želim da vam ispričam
09:51
is how can we find targets for treating post-traumatic stress disorder --
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o tome kako možemo naći mete za tretman PTSP --
09:54
a form of uncontrolled anxiety and fear.
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oblik nekontrolisane anksioznosti i straha.
09:57
And one of the things that we did
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Jedna od stvari koje smo uradili
09:59
was to adopt a very classical model of fear.
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je bila da smo usvojili veoma klasičan model straha.
10:02
This goes back to the Pavlovian days.
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Ovo je iz vremena Pavlova.
10:05
It's called Pavlovian fear conditioning --
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Naziva se Pavlovljevim uslovljavanjem --
10:07
where a tone ends with a brief shock.
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tu se zvuk 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 neprijatan.
10:11
And over time -- in this case, a mouse,
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Tokom vremena -- u ovom slučaju miš --
10:13
which is a good animal model, commonly used in such experiments --
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koji je dobar životinjski model, obično se koristi u ovakvim eksperimentima --
10:15
the animal learns to fear the tone.
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životinja uči da se plaši zvuka.
10:17
The animal will react by freezing,
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Životinja reaguje kočenjem,
10:19
sort of like a deer in the headlights.
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nešto kao jelen uhvaćen u farove.
10:21
Now the question is, what targets in the brain can we find
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Pitanje je koju metu možemo da nađemo u mozgu
10:24
that allow us to overcome this fear?
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koja bi nam omogućila da prevlada strah?
10:26
So what we do is we play that tone again
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Stoga smo ponovo proizvodili ton
10:28
after it's been associated with fear.
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nakon što je povezan sa strahom.
10:30
But we activate targets in the brain, different ones,
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Ali aktiviramo ciljeve u mozgu, neke druge,
10:32
using that optical fiber array I told you about in the previous slide,
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koristeći nizove optičkih vlakana o kojima sam vam pričao uz prethodni slajd,
10:35
in order to try and figure out which targets
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u cilju da probamo da odredimo koji ciljevi
10:37
can cause the brain to overcome that memory of fear.
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mogu da učine da mozak prevaziđe sećanje na strah.
10:40
And so this brief video
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I tako ovaj kratki video snimak
10:42
shows you one of these targets that we're working on now.
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pokazuje jedan od tih ciljeva na kojima mi sada radimo.
10:44
This is an area in the prefrontal cortex,
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Ovo je oblast u prefrontalnom korteksu,
10:46
a region where we can use cognition to try to overcome aversive emotional states.
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region u kome koristimo spoznato da pokušamo da prevaziđemo averzivna emocionalna 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 -- bljesak svetla se pojavio tamo.
10:51
There's no audio on this, but you can see the animal's freezing.
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Ovaj snimak nema ton ali možete videti da se životinja ukočila.
10:53
This tone used to mean bad news.
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Ovaj ton je značio najavu lošeg.
10:55
And there's a little clock in the lower left-hand corner,
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U donjem levom uglu vidite mali sat,
10:57
so you can see the animal is about two minutes into this.
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tako da možete da vidite da je životinja u ovom stanju oko dva minuta.
11:00
And now this next clip
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A sada sledeći video snimak
11:02
is just eight minutes later.
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koji je napravljen 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 je proizveden i svetlo će bljesnuti ponovo.
11:07
Okay, there it goes. Right now.
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OK, evo ga. Baš sad.
11:10
And now you can see, just 10 minutes into the experiment,
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I sada možete videti, nakon samo deset minuta eksperimenta,
11:13
that we've equipped the brain by photoactivating this area
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da smo mozgu omogućili fotoaktiviranjem oblasti
11:16
to overcome the expression
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da prevaziđe iskazivanje
11:18
of this fear memory.
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sećanja na strah.
11:20
Now over the last couple of years, we've gone back to the tree of life
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Tokom poslednjih par godina vrativši se stablu života,
11:23
because we wanted to find ways to turn circuits in the brain off.
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pošto smo želeli da nađemo način da isključimo kola u mozgu.
11:26
If we could do that, this could be extremely powerful.
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Ako bi mogli to da uradimo to bi bilo izuzetno moćno.
11:29
If you can delete cells just for a few milliseconds or seconds,
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Ako možete da izbrišete ćelije na samo nekoliko milisekundi ili sekundi,
11:32
you can figure out what necessary role they play
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možete da otkrijete koju to neophodnu ulogu one imaju
11:34
in the circuits in which they're embedded.
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u kolu u koje su smeštene.
11:36
And we've now surveyed organisms from all over the tree of life --
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Pregledom organizama širom stabla života --
11:38
every kingdom of life except for animals, we see slightly differently.
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svako životno carstvo osim životinjskog jer mi vidimo nešto drugačije.
11:41
And we found all sorts of molecules, they're called halorhodopsins or archaerhodopsins,
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I našli smo svakojake vrste molekula, zovu se halorhodopsini i arherohodopsini,
11:44
that respond to green and yellow light.
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koje odgovaraju na zeleno i žuto svetlo.
11:46
And they do the opposite thing of the molecule I told you about before
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Oni rade nešto različito od molekula o kojima sam vam pričao ranije
11:48
with the blue light activator channelrhodopsin.
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sa channelrhodopsin-om koji se aktivira plavim svetlom.
11:52
Let's give an example of where we think this is going to go.
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Evo primera o tome šta mislimo kuda ovo vodi.
11:55
Consider, for example, a condition like epilepsy,
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Uzmimo na primer stanje kao što je epilepsija,
11:58
where the brain is overactive.
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gde je mozak previše aktivan.
12:00
Now if drugs fail in epileptic treatment,
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Ako lekovi ne uspevaju da tretiraju epilepsiju,
12:02
one of the strategies is to remove part of the brain.
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jedna od strategija je da se odstrani deo mozga.
12:04
But that's obviously irreversible, and there could be side effects.
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Ali to je očigledno nepovratna akcija i moglo bi da bude neželjenih efekata.
12:06
What if we could just turn off that brain for a brief amount of time,
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Šta ako možemo da jednostavno isključimo taj mozak na tren,
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 tako uspemo da mozak obnovi svoje početno stanje --
12:15
sort of like a dynamical system that's being coaxed down into a stable state.
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nešto kao dinamički sistem koji potisnemo nadole u stabilno stanje.
12:18
So this animation just tries to explain this concept
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Ova animacija samo pokušava da objasni koncept
12:21
where we made these cells sensitive to being turned off with light,
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u kome smo učinili ove ćelije osetljivim na gašenje svetlom,
12:23
and we beam light in,
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i onda bljesnemo svetlo,
12:25
and just for the time it takes to shut down a seizure,
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i to samo onoliko vremena koliko je potrebno da se zaustavi napad
12:27
we're hoping to be able to turn it off.
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u nadi da ćemo biti u stanju da mozak ugasimo.
12:29
And so we don't have data to show you on this front,
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Nemamo podatke da vam ih sada pokažemo
12:31
but we're very excited about this.
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ali ovo je veoma uzbudljivo.
12:33
Now I want to close on one story,
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Želim da završim jednom pričom,
12:35
which we think is another possibility --
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za koju mislimo da je još jedna od mogućnosti --
12:37
which is that maybe these molecules, if you can do ultra-precise control,
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a to je da ovi molekuli možda, ako može da se napravi ultra precizno upravljanje,
12:39
can be used in the brain itself
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mogu da budu upotrebljeni u samom mozgu
12:41
to make a new kind of prosthetic, an optical prosthetic.
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za pravljenje nove vrste pomagala, optičkih pomagala.
12:44
I already told you that electrical stimulators are not uncommon.
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Već sam vam rekao da elektirčna stimulacija nije neobična.
12:47
Seventy-five thousand people have Parkinson's deep-brain stimulators implanted.
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75.000 ljudi ima, duboko u mozgu, ugrađene stimulatore za kontrolu Parkinsonove bolesti.
12:50
Maybe 100,000 people have Cochlear implants,
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Nekih 100.000 ljudi ima kohlearne implante,
12:52
which allow them to hear.
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koji im omogućavaju da čuju.
12:54
There's another thing, which is you've got to get these genes into cells.
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Ima tu još nesšto a to je da morate da ubacite ove gene u ćelije.
12:57
And new hope in gene therapy has been developed
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Pojavila se nova nada u genskoj terapiji
13:00
because viruses like the adeno-associated virus,
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jer su virusi poput adeno povezanih virusa,
13:02
which probably most of us around this room have,
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koje verovatno većina nas u ovoj prostoriji ima,
13:04
and it doesn't have any symptoms,
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a da pri tom nema nikakve simptome,
13:06
which have been used in hundreds of patients
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upotrebljeni na stotinama pacijenata
13:08
to deliver genes into the brain or the body.
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da bi dopremili gene u mozak ili telo.
13:10
And so far, there have not been serious adverse events
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I za sada još nije bilo ozbiljnih štetnih događaja
13:12
associated with the virus.
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koji su povezani sa virusom.
13:14
There's one last elephant in the room, the proteins themselves,
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U sobi se nalazi još jedan slon, sami proteini,
13:17
which come from algae and bacteria and fungi,
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koje dobijamo od algi i bakterija i plesni,
13:19
and all over the tree of life.
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sa celog stabla života.
13:21
Most of us don't have fungi or algae in our brains,
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Većina nas nema plesni ili alge u mozgu,
13:23
so what is our brain going to do if we put that in?
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i šta će mozak da uradi ako mu ih ubacimo?
13:25
Are the cells going to tolerate it? Will the immune system react?
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Da li će ih ćelije tolerisati? Da li će reagovati imunološki sistem?
13:27
In its early days -- these have not been done on humans yet --
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U početku smo -- ovo još nije probano na ljudima --
13:29
but we're working on a variety of studies
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ali radimo na raznim studijama
13:31
to try and examine this,
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ispitujući ovo.
13:33
and so far we haven't seen overt reactions of any severity
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Za sada nismo videli suprotne ili ikakve značajne reakcije
13:36
to these molecules
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na ove molekule
13:38
or to the illumination of the brain with light.
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ili na obasjavanje mozga svetlošću.
13:41
So it's early days, to be upfront, but we're excited about it.
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Rano je, da budemo jasni, ali smo veoma uzbuđeni svim ovim.
13:44
I wanted to close with one story,
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Želim da završim jednom pričom,
13:46
which we think could potentially
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za koju mislimo da predstavlja potencijalnu
13:48
be a clinical application.
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kliničku primenu.
13:50
Now there are many forms of blindness
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Postoje razne vrste slepila
13:52
where the photoreceptors,
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gde fotoreceptori,
13:54
our light sensors that are in the back of our eye, are gone.
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naši svetlosni senzori koji su u dnu naših očiju, više ne postoje.
13:57
And the retina, of course, is a complex structure.
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A retina je, naravno, kompleksna struktura.
13:59
Now let's zoom in on it here, so we can see it in more detail.
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Hajde da zumiramo to, da bi mogli da vidimo više detalja.
14:01
The photoreceptor cells are shown here at the top,
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Fotoreceptorske ćelije su prikazane na vrhu,
14:04
and then the signals that are detected by the photoreceptors
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a onda se signal koji detektuju fotorecpetori
14:06
are transformed by various computations
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transformiše različitim proračunima,
14:08
until finally that layer of cells at the bottom, the ganglion cells,
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dok na kraju taj sloj ćelija na dnu, ganglionske ćelije,
14:11
relay the information to the brain,
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proslede informaciju mozgu,
14:13
where we see that as perception.
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gde vidimo opaženo.
14:15
In many forms of blindness, like retinitis pigmentosa,
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U mnogim vrstama slepila, kao recimo retinska pigmentoza,
14:18
or macular degeneration,
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ili degeneracija makule,
14:20
the photoreceptor cells have atrophied or been destroyed.
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fotorecpetorske ćelije su atrofirane ili su uništene.
14:23
Now how could you repair this?
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Kako je ovo moguće popraviti?
14:25
It's not even clear that a drug could cause this to be restored,
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Nije jasno da lekovi mogu da uzrokuju obnavljanje,
14:28
because there's nothing for the drug to bind to.
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pošto ne postoji ništa za šta bi lek mogao da se veže.
14:30
On the other hand, light can still get into the eye.
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A opet, svetlo i dalje dospeva u oko.
14:32
The eye is still transparent and you can get light in.
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Oko je i dalje providno i možete da uvedete svetlost unutra.
14:35
So what if we could just take these channelrhodopsins and other molecules
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Šta ako možemo da uzmemo channelfhodopsin-e i druge molekule
14:38
and install them on some of these other spare cells
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i instaliramo ih na neke od slobodnih ćelija
14:40
and convert them into little cameras.
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i tako ih pretvorimo u male kamere.
14:42
And because there's so many of these cells in the eye,
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A pošto ima mnogo ovih ćelija u oku,
14:44
potentially, they could be very high-resolution cameras.
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potencijalno, one mogu biti kamere visoke rezolucije.
14:47
So this is some work that we're doing.
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To je nešto na čemu radimo.
14:49
It's being led by one of our collaborators,
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Time rukovodi jedan od naših saradnika,
14:51
Alan Horsager at USC,
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Alan Horsager sa USC-a,
14:53
and being sought to be commercialized by a start-up company Eos Neuroscience,
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a radi komercijalizacije ga traži start-ap kompanija Eos Neuroscience,
14:56
which is funded by the NIH.
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koju je osnovao NIH.
14:58
And what you see here is a mouse trying to solve a maze.
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Ono što vidite ovde je miš koji pokušava da reši lavirint.
15:00
It's a six-arm maze. And there's a bit of water in the maze
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To je šestokraki lavirint. A ima i nešto vode u lavirintu
15:02
to motivate the mouse to move, or he'll just sit there.
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da bi motivisali miša da se kreće jer bi u suprotnom on samo sedeo unutra.
15:04
And the goal, of course, of this maze
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Cilj ovog lavirinta je, naravno,
15:06
is to get out of the water and go to a little platform
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da izađe iz vode na malu platformu
15:08
that's under the lit top port.
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koja je pod osvetljenim gornjim otvorom.
15:10
Now mice are smart, so this mouse solves the maze eventually,
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Miševi su pametni, i tako ovaj miš konačno reši lavirint,
15:13
but he does a brute-force search.
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ali on primenjuje pretragu putem pokušaja i promašaja.
15:15
He's swimming down every avenue until he finally gets to the platform.
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On upliva u svako udubljenje dok na kraju ne nađe platformu.
15:18
So he's not using vision to do it.
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Znači ne koristi vid da bi to obavio.
15:20
These different mice are different mutations
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Ovi razni miševi imaju raličite mutacije
15:22
that recapitulate different kinds of blindness that affect humans.
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koje prikazuju različite vrste slepila koje pogađa ljude.
15:25
And so we're being careful in trying to look at these different models
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Pažljivo smo se trudili da sagledamo ove različite modele,
15:28
so we come up with a generalized approach.
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i tako smo došli do generalizovanog pristupa.
15:30
So how are we going to solve this?
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Kako ćemo da rešimo ovo?
15:32
We're going to do exactly what we outlined in the previous slide.
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Pokušaćemo da uradimo baš ono što smo predstavili prethodnim slajdom.
15:34
We're going to take these blue light photosensors
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Uzećemo ove fotosenzore za plavo svetlo
15:36
and install them on a layer of cells
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i instaliraćemo ih na sloj ćelija
15:38
in the middle of the retina in the back of the eye
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u sredini retine, u dnu oka
15:41
and convert them into a camera --
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i pretvorićemo ih u kamere.
15:43
just like installing solar cells all over those neurons
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Baš kao što se instaliraju solarne ćelije svuda po ovim neuronima
15:45
to make them light sensitive.
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da bi ih učinili osetljivim na svetlost.
15:47
Light is converted to electricity on them.
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Svetlo se pretvara u elektricitet na njima.
15:49
So this mouse was blind a couple weeks before this experiment
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Ovaj miš je bio slep nekoliko nedelja pre ovog eksperimenta
15:52
and received one dose of this photosensitive molecule in a virus.
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i primio je jednu dozu ovih fotoosetljivih molekula u virusu.
15:55
And now you can see, the animal can indeed avoid walls
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Kao što možete videti, životinja zaista može da izbegne zidove
15:57
and go to this little platform
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i dođe do male platforme
15:59
and make cognitive use of its eyes again.
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ponovo upotrebivši oči za tu spoznaju.
16:02
And to point out the power of this:
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A da bih naglasio značaj ovoga:
16:04
these animals are able to get to that platform
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ove životinje su bile u stanju da dođu na platformu
16:06
just as fast as animals that have seen their entire lives.
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istom brzinom kao i životinje koje vide celog života.
16:08
So this pre-clinical study, I think,
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Ova predklinička studija je, mislim,
16:10
bodes hope for the kinds of things
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dobar predznak za vrstu stvari
16:12
we're hoping to do in the future.
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za koje se nadamo da ćemo raditi u budućnosti.
16:14
To close, I want to point out that we're also exploring
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Za kraj, želim da naglasim da mi istražujemo i
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 oruđa,
16:21
but we share them freely with hundreds of groups all over the world,
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ali ih razmenjujemo slobodno sa stotinama grupa širom sveta,
16:23
so people can study and try to treat different disorders.
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tako da ljudi mogu da proučavaju i pokušavaju da tretiraju različite poremećaje.
16:25
And our hope is that, by figuring out brain circuits
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Nadamo se da, shvativši kola u mozgu
16:28
at a level of abstraction that lets us repair them and engineer them,
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na apstraktnom nivou koji nam dopušta da ih popravimo i da ih stvaramo,
16:31
we can take some of these intractable disorders that I told you about earlier,
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možemo neke od ovih tvrdoglavih poremećaja o kojima sam ranije pričao,
16:34
practically none of which are cured,
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od kojih nijedan praktično nije izlečen,
16:36
and in the 21st century make them history.
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da pošaljemo u istoriju.
16:38
Thank you.
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Hvala.
16:40
(Applause)
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(Aplauz)
16:53
Juan Enriquez: So some of the stuff is a little dense.
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Huan Enrikez: Nešto od ovoga je malo previše.
16:56
(Laughter)
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(Smeh)
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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ideje da je moguće kontrolisati napade ili epilepsiju
17:03
with light instead of drugs,
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svetlom umesto lekovima,
17:05
and being able to target those specifically
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i mogućnosti da se baš one naciljaju
17:08
is a first step.
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je prvi korak.
17:10
The second thing that I think I heard you say
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Druga stvar koju mislim da sam čuo da si rekao
17:12
is you can now control the brain in two colors,
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je da je sada moguće kontrolisati mozak dvema bojama.
17:15
like an on/off switch.
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Nešto kao prekidač za uključivanje i isključivanje.
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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HE: To svaki impuls koji ide kroz mozak čini binarnim kodom.
17:22
EB: Right, yeah.
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EB: Da, tako je.
17:24
So with blue light, we can drive information, and it's in the form of a one.
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Plavim svetlom možemo slati informacije, i to je recimo jedinica.
17:27
And by turning things off, it's more or less a zero.
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A isključivanje je nešto kao nula.
17:29
So our hope is to eventually build brain coprocessors
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Tako da se mi nadamo da ćemo moći da stvorimo koprocesore u mozgu
17:31
that work with the brain
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koji će raditi sa mozgom,
17:33
so we can augment functions in people with disabilities.
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tako da ćemo moći da povećamo funkcije ljudima sa invaliditetom.
17:36
JE: And in theory, that means that,
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HE: U teoriji to znači da,
17:38
as a mouse feels, smells,
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kao što miš oseća, omiriše,
17:40
hears, touches,
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čuje, dodirne,
17:42
you can model it out as a string of ones and zeros.
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vi možete da napravite model u vidu jedinica i nula.
17:45
EB: Sure, yeah. We're hoping to use this as a way of testing
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EB: Naravno, da. Nadamo se da to upotrebimo kao način testiranja.
17:47
what neural codes can drive certain behaviors
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koji su prirodni kodovi koji upravljaju određenim ponašanjima
17:49
and certain thoughts and certain feelings,
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i određenim mislima i određenim osećanjima,
17:51
and use that to understand more about the brain.
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i da to upotrebimo za bolje spoznavanje mozga.
17:54
JE: Does that mean that some day you could download memories
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HE: Da li to znači da ćemo jednog dana moći da daunlodujemo sećanja
17:57
and maybe upload them?
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i možda ih aploudujemo?
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 da radimo intenzivno.
18:01
We're now working on some work
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Sada radimo na radu
18:03
where we're trying to tile the brain with recording elements too.
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gde pokušavamo da popločamo mozak i elementima za beleženje.
18:05
So we can record information and then drive information back in --
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Tako da možemo da zabeležimo informacije i onda da možemo da upravimo informacije nazad --
18:08
sort of computing what the brain needs
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nešto kao proračunavanje onoga što je mozgu potrebno
18:10
in order to augment its information processing.
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da bi poboljšali njegov informacioni proces.
18:12
JE: Well, that might change a couple things. Thank you. (EB: Thank you.)
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HE: To bi moglo da izmeni neke stvari. Hvala ti. (EB: Hvala.)
18:15
(Applause)
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(Aplauz)
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